Leptin

 

Leptin

Introduction

Leptin (from Greek λεπτός leptos, "thin" or "light" or "small"), also known as obese protein, is a protein hormone predominantly made by adipocytes (cells of adipose tissue). Its primary role is likely to regulate long-term energy balance.

As one of the major signals of energy status, leptin levels influence appetite, satiety, and motivated behaviors oriented toward the maintenance of energy reserves (e.g., feeding, foraging behaviors).

The amount of circulating leptin correlates with the amount of energy reserves, mainly triglycerides stored in adipose tissue. High leptin levels are interpreted by the brain that energy reserves are high, whereas low leptin levels indicate that energy reserves are low, in the process adapting the organism to starvation through a variety of metabolic, endocrine, neurobiochemical, and behavioral changes. Leptin is coded for by the LEP gene. Leptin receptors are expressed by a variety of brain and peripheral cell types. These include cell receptors in the arcuate and ventromedial nuclei, as well as other parts of the hypothalamus and dopaminergic neurons of the ventral tegmental area, consequently mediating feeding.

Although regulation of fat stores is deemed to be the primary function of leptin, it also plays a role in other physiological processes, as evidenced by its many sites of synthesis other than fat cells, and the many cell types beyond hypothalamic cells that have leptin receptors. Many of these additional functions are yet to be fully defined.

In obesity, a decreased sensitivity to leptin occurs (similar to insulin resistance in type 2 diabetes), resulting in an inability to detect satiety despite high energy stores and high levels of leptin.

Sites of synthesis

Leptin is produced primarily in the adipocytes of white adipose tissue. It also is produced by brown adipose tissue, placenta (syncytiotrophoblasts), ovaries, skeletal muscle, stomach (the lower part of the fundic glands), mammary epithelial cells, bone marrow,[19] gastric chief cells, and P/D1 cells.

Blood levels

Leptin circulates in blood in free form and bound to proteins. Leptin levels vary exponentially, not linearly, with fat mass. Leptin levels in blood are higher between midnight and early morning, perhaps suppressing appetite during the night. The diurnal rhythm of blood leptin levels may be modified by meal-timing. Increased levels of melatonin causes a downregulation of leptin, however, melatonin also appears to increase leptin levels in the presence of insulin, therefore causing a decrease in appetite during sleeping. Partial sleep deprivation has also been associated with decreased blood leptin levels.

Functions

1.       Predominantly, the "energy expenditure hormone" leptin is made by adipose cells, and is thus labeled fat cell-specific. The central location of action (effect) of the fat cell-specific hormone leptin is the hypothalamus. The primary function of the hormone leptin is the regulation of adipose tissue mass through central hypothalamus mediated effects on hunger, food energy use, physical exercise, and energy balance.

2.       Outside the brain, in the periphery of the body, leptin's secondary functions are: modulation of energy expenditure, modulation between fetal and maternal metabolism, and that of a permissive factor in puberty, activator of immune cells, activator of beta islet cells, and growth factor.

3.       Leptin along with kisspeptin controls the onset of puberty. High levels of leptin, as usually observed in obese females, can trigger neuroendocrine cascade resulting in early menarche. This may eventually lead to shorter stature as estrogen secretion starts during menarche and causes early closure of epiphyses.

4.       Leptin can affect bone metabolism via direct signalling from the brain. Leptin decreases cancellous bone, but increases cortical bone. This "cortical-cancellous dichotomy" may represent a mechanism for enlarging bone size, and thus bone resistance, to cope with increased body weight.

5.       Factors that acutely affect leptin levels are also factors that influence other markers of inflammation, e.g., testosterone, sleep, emotional stress, caloric restriction, and body fat levels. While it is well-established that leptin is involved in the regulation of the inflammatory response, it has been further theorized that leptin's role as an inflammatory marker is to respond specifically to adipose-derived inflammatory cytokines.

6.       Similar to what is observed in chronic inflammation, chronically elevated leptin levels are associated with obesity, overeating, and inflammation-related diseases, including hypertension, metabolic syndrome, and cardiovascular disease. While leptin is associated with body fat mass, the size of individual fat cells, and overeating, it is not affected by exercise.

specific conditions

In humans, many instances are seen where leptin dissociates from the strict role of communicating nutritional status between body and brain and no longer correlates with body fat levels:

·       Leptin plays a critical role in the adaptive response to starvation.

·       Leptin level is decreased after short-term fasting (24–72 hours), even when changes in fat mass are not observed.

·       Serum level of leptin is reduced by sleep deprivation.

·       Leptin levels are paradoxically increased in obesity.

·       Leptin level is increased by emotional stress.

·       Leptin level is chronically reduced by physical exercise training.

·       Leptin level is decreased by increases in testosterone levels and increased by increases in estrogen levels.

·       Leptin level is increased by insulin.

·       Leptin release is increased by dexamethasone.

·       In obese patients with obstructive sleep apnea, leptin level is increased, but decreased after the administration of continuous positive airway pressure.[119][120] In non-obese individuals, h

Ghrelin

 

Ghrelin

Introduction

Ghrelin (/ˈɡrɛlɪn/; or lenomorelin, INN) is a hormone primarily produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is also dubbed the "hunger hormone" because it increases the drive to eat.[6] Blood levels of ghrelin are highest before meals when hungry, returning to lower levels after mealtimes. 4Ghrelin may help prepare for food intake by increasing gastric motility and stimulating the secretion of gastric acid. Ghrelin activates cells in the anterior pituitary gland and hypothalamic arcuate nucleus, including neuropeptide Y neurons that initiate appetite. Ghrelin stimulates brain structures having a specific receptor – the growth hormone secretagogue receptor 1A (GHSR-1A). Ghrelin also participates in regulation of reward cognition, learning and memory, the sleep-wake cycle, taste sensation, reward behavior, and glucose metabolism.

Ghrelin was discovered after the ghrelin receptor (called growth hormone secretagogue type 1A receptor or GHS-R) was determined in 1999. The hormone name is based on its role as a growth hormone-releasing peptide- gʰre-, meaning "to grow".

Ghrelin cells

The ghrelin cell is also known as an A-like cell (pancreas), X-cell (for unknown function), X/A-like cell (rats), Epsilon cell (pancreas), P/D sub 1 cell (humans) and Gr cell (abbreviation for ghrelin cell).

Ghrelin cells are found mainly in the stomach and duodenum, but also in the jejunum, lungs, pancreatic islets, gonads, adrenal cortex, placenta, and kidney. It has also been shown that ghrelin is produced locally in the brain. Additionally, research suggests that ghrelin may be produced in the myocardium and have an 'autocrine/ paracrine' like effect within the heart. Ghrelin cells are also found in oxyntic glands (20% of cells), pyloric glands, and small intestine.

Function and mechanism of action

1.       Ghrelin is a participant in regulating the complex process of energy homeostasis which adjusts both energy input – by adjusting hunger signals – and energy output – by adjusting the proportion of energy going to ATP production, fat storage, glycogen storage, and short-term heat loss. The net result of these processes is reflected in body weight, and is under continuous monitoring and adjustment based on metabolic signals and needs. At any given moment in time, it may be in equilibrium or disequilibrium. Gastric-brain communication is an essential part of energy homeostasis, and several communication pathways are probable, including the gastric intracellular mTOR/S6K1 pathway mediating the interaction among ghrelin, nesfatin and endocannabinoid gastric systems, and both afferent and efferent vagal signals.

2.       Ghrelin and synthetic ghrelin mimetics (growth hormone secretagogues) increase body weight and fat mass by triggering receptors in the arcuate nucleus that include neuropeptide Y (NPY) and agouti-related protein (AgRP) neurons. Ghrelin responsiveness of these neurons is both leptin- and insulin-sensitive. Ghrelin reduces the sensitivity of gastric vagal afferents, so they are less sensitive to gastric distension.

3.       In addition to its function in energy homeostasis, ghrelin also activates the cholinergic–dopaminergic reward link in inputs to the ventral tegmental area and in the mesolimbic pathway, a circuit that communicates the hedonic and reinforcing aspects of natural rewards, such as food and addictive drugs such as ethanol. Ghrelin receptors are located on neurons in this circuit. Hypothalamic ghrelin signaling is required for reward from alcohol and palatable/rewarding foods.

4.       Ghrelin has been linked to inducing appetite and feeding behaviors. Circulating ghrelin levels are the highest right before a meal and the lowest right after. Injections of ghrelin in humans have been shown to increase food intake in a dose-dependent manner. So the more ghrelin that is injected the more food that is consumed. However, ghrelin does not increase meal size, only meal number. Ghrelin also increases motivation to seek out food.

5.       Body weight is regulated through energy balance, the amount of energy taken in versus the amount of energy expended over an extended period of time. Studies have shown that ghrelin levels are positively correlated with weight. This data suggests that ghrelin functions as an adiposity signal, a messenger between the body's energy stores and the brain.

6.       Action on Glucose metabolism

The entire ghrelin system (dAG, AG, GHS-R and GOAT) has a gluco-regulatory action,

7.       Effects of and on Sleep

Preliminary research indicates that ghrelin participates in the regulation of circadian rhythms. A review reported finding strong evidence that sleep restriction affected ghrelin or leptin levels, or energy expenditure.

8.       Effects on Cardiovascular system

Ghrelin functions as a cardio-protective peptide by being an anti-inflammatory agent, promoting angiogenesis, inhibiting arrhythmia, and improving heart failure.

 

Thyroid hormones

 

 

Thyroid hormones

Thyroid hormones are two hormones produced and released by the thyroid gland: triiodothyronine (T3) and thyroxine (T4). They are tyrosine-based hormones that are primarily responsible for regulation of metabolism. T3 and T4 are partially composed of iodine, which is derived from food American chemist Edward Calvin Kendall was responsible for the isolation of thyroxine in 1915. Levothyroxine, a synthetic derivative of Thyroxine, is on the World Health Organization's List of Essential Medicines.

The major form of thyroid hormone in the blood is thyroxine (T4), whose half-life of around one week, is longer than that of T3. In humans, the ratio of T4 to T3 released into the blood is approximately 14:1. T4 is converted to the active T3 (three to four times more potent than T4) within cells by deiodinases (5′-deiodinase). These are further processed by decarboxylation and deiodination to produce iodothyronamine (T1a) and thyronamine (T0a). All three isoforms of the deiodinases are selenium-containing enzymes, thus dietary selenium is essential for T3 production. Calcitonin, a peptide hormone produced and secreted by the thyroid, is usually not included in the meaning of "thyroid hormone".

Thyroid hormones are one of the factors responsible for the modulation of energy expenditure. This is achieved through several mechanisms, such as mitochondrial biogenesis and adaptive thermogenesis.

Thyroid metabolism

Central metabolism

- Thyroglobulin is synthesized in the rough endoplasmic reticulum and follows the secretory pathway to enter the colloid in the lumen of the thyroid follicle by exocytosis.

- Meanwhile, a sodium-iodide (Na/I) symporter pumps iodide (I−) actively into the cell, which previously has crossed the endothelium by largely unknown mechanisms.

- This iodide enters the follicular lumen from the cytoplasm by the transporter pendrin, in a purportedly passive manner.

- In the colloid, iodide (I−) is oxidized to iodine (I0) by an enzyme called thyroid peroxidase.

- Iodine (I0) is very reactive and iodinates the thyroglobulin at tyrosyl residues in its protein chain (in total containing approximately 120 tyrosyl residues).

- In conjugation, adjacent tyrosyl residues are paired together.

- Thyroglobulin re-enters the follicular cell by endocytosis.

- Proteolysis by various proteases liberates thyroxine and triiodothyronine molecules

- Efflux of thyroxine and triiodothyronine from follicular cells, which appears to be largely through monocarboxylate transporter 8 (MCT 8) and 10, and entry into the blood.

Thyroid hormones (T4 and T3) are produced by thyroid epithelial cells (a.k.a. thyroid follicular cells) and are regulated by thyroid-stimulating hormone (TSH) made by the thyrotropes of the anterior pituitary gland. The effects of T4 in vivo are mediated via T3 (T4 is converted to T3 in target tissues). T3 is three to five times more active than T4. T4, thyroxine (3,5,3′,5′-tetraiodothyronine), is produced by follicular cells of the thyroid gland. It is produced from the precursor thyroglobulin (this is not the same as thyroxine-binding globulin [TBG]), which is cleaved by enzymes to produce active T4.

The steps in this process are as follows:

The Na+/I− symporter transports two sodium ions across the basement membrane of the follicular cells along with an iodide ion. This is a secondary active transporter that utilises the concentration gradient of Na+ to move I− against its concentration gradient. This is called iodide trapping.[36] Sodium is cotransported with iodide from the basolateral side of the membrane into the cell,[clarification needed] and then concentrated in the thyroid follicles to about thirty times its concentration in the blood.

I− is moved across the apical membrane into the colloid of the follicle by pendrin. Hydrogen peroxide is also introduced into the follicle by the action of DUX (Dual Oxidase).

Iodide is non-reactive, and the reactive I2 species is required for the next step. Thyroid peroxidase (TPO) reduces hydrogen peroxide to water by transferring one electron from two I− atoms that react to form I2.

Iodine (I2) is converted into HOI, by hydration with water. Both I2 and HOI iodinate specific tyrosyl residues of the thyroglobulin within the colloid to form 3-monoiodityrosyl (MIT-yl) and 3,5-diiodityrosyl (DIT-yl) residues—introducting iodine atoms at one or both locations ortho to the hydroxyls of tyrosine. The thyroglobulin was synthesised in the ER of the follicular cell and secreted into the colloid.

TPO also converts tyrosyl, MIT-yl, and DIT-yl residues into their free radical forms. These forms attack other MIT-yl and DIT-yl residues. When a DIT-yl radical attacks a DIT, T4-yl (peptidic T4) is formed. When a MIT-yl radical attacks a DIT, T3-yl is formed. Other reactions are possible, but do not form physiologically active products.

Iodinated thyroglobulin binds megalin for endocytosis back into the cell.

TSH released from the anterior pituitary (a.k.a. the adenohypophysis) binds the TSH receptor (a Gs protein-coupled receptor) on the basolateral membrane of the cell and stimulates the endocytosis of the colloid.

The endocytosed vesicles fuse with the lysosomes of the follicular cell. The lysosomal enzymes cleave any MIT, DIT, T3, T4 as well as the inactive analogues from the iodinated thyroglobulin.

The thyroid hormones cross the follicular cell membrane towards the blood vessels by monocarboxylate transporter 8 (MCT 8) and 10 which play major roles in the efflux of the thyroid hormones from thyroid cells.

Thyroglobulin (Tg) is a 660 kDa, dimeric protein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Thyroxine is produced by attaching iodine atoms to the ring structures of this protein's tyrosine residues; thyroxine (T4) contains four iodine atoms, while triiodothyronine (T3), otherwise identical to T4, has one less iodine atom per molecule.[48] The thyroglobulin protein accounts for approximately half of the protein content of the thyroid gland.[49] Each thyroglobulin molecule contains approximately 100–120 tyrosine residues, a small number (<20) of which are subject to iodination catalysed by thyroperoxidase. The same enzyme then catalyses "coupling" of one modified tyrosine with another, via a free-radical-mediated reaction, and when these iodinated bicyclic molecules are released by hydrolysis of the protein, T3 and T4 are the result. Therefore, each thyroglobulin protein molecule ultimately yields very small amounts of thyroid hormone (experimentally observed to be on the order of 5–6 molecules of either T4 or T3 per original molecule of thyroglobulin).

Hydrolysis (cleavage to individual amino acids) of the modified protein by proteases then liberates T3 and T4, as well as the non-coupled tyrosine derivatives MIT and DIT. The hormones T4 and T3 are the biologically active agents central to metabolic regulation.

 

Peripheral metabolism

Thyroxine is believed to be a prohormone and a reservoir for the most active and main thyroid hormone, T3. T4 is converted as required in the tissues by iodothyronine deiodinase. Deficiency of deiodinase can mimic hypothyroidism due to iodine deficiency.T3 is more active than T4,[56] though it is present in less quantity than T4.

Initiation of production in fetuses

Thyrotropin-releasing hormone (TRH) is released from hypothalamus by 6–8 gestational weeks, and thyroid-stimulating hormone (TSH) secretion from the fetal pituitary gland is evident by 12 gestational weeks; fetal production of thyroxine (T4) reaches a clinically significant level at 18–20 weeks. Fetal triiodothyronine (T3) remains low (less than 15 ng/dL) until 30 weeks of gestation, and increases to 50 ng/dL at term. Fetal self-sufficiency of thyroid hormones protects the fetus against, for example, neurodevelopmental abnormalities caused by maternal hypothyroidism

 

Circulation and transport

Plasma transport

Most of the thyroid hormone circulating in the blood is bound to transport proteins, and only a very small fraction is unbound and biologically active. Therefore, measuring concentrations of free thyroid hormones is important for diagnosis, while measuring total levels can be misleading.

Thyroid hormone in the blood is usually distributed as follows:

Type	Percent
bound to thyroxine-binding globulin (TBG)	70%
bound to transthyretin or "thyroxine-binding prealbumin" (TTR or TBPA)	10–15%
albumin	15–20%
unbound T4 (fT4)	0.03%
unbound T3 (fT3)	0.3%

Despite being lipophilic, T₃ and T₄ cross the cell membrane via carrier-mediated transport, which is ATP-dependent

Membrane transport

thyroid hormones cannot traverse cell membranes in a passive manner like other lipophilic substances. The iodine in o-position makes the phenolic OH-group more acidic, resulting in a negative charge at physiological pH. However, at least 10 different active, energy-dependent and genetically regulated iodothyronine transporters have been identified in humans. They guarantee that intracellular levels of thyroid hormones are higher than in blood plasma or interstitial fluids.

Mechanism of action

The thyroid hormones function via a well-studied set of nuclear receptors, termed the thyroid hormone receptors. These receptors, together with corepressor molecules, bind DNA regions called thyroid hormone response elements (TREs) near genes. This receptor-corepressor-DNA complex can block gene transcription. Triiodothyronine (T3), which is the active form of thyroxine (T4), goes on to bind to receptors. The deiodinase catalyzed reaction removes an iodine atom from the 5′ position of the outer aromatic ring of thyroxine's (T4) structure. When triiodothyronine (T3) binds a receptor, it induces a conformational change in the receptor, displacing the corepressor from the complex. This leads to recruitment of coactivator proteins and RNA polymerase, activating transcription of the gene.

Functions of Thyroid Hormones

Thyroid hormones act on nearly every cell in the body. They act to

·       increase the basal metabolic rate

·       affect protein synthesis

·       help regulate long bone growth in synergy with growth hormone

·       effect neural maturation

·       increase the body's sensitivity to catecholamines (such as norepinephrine and epinephrine) by permissiveness, especially under cold exposure.

·       essential to proper development and differentiation of all cells of the human body.

·       These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds.

·       They  stimulate vitamin metabolism.

·       Thyroid hormones lead to heat generation in humans.

Functions of triiodothyronine

Effects of triiodothyronine (T3) which is the metabolically active form:

·       Increases cardiac output

·       Increases heart rate

·       Increases ventilation rate

·       Increases basal metabolic rate

·       Potentiates the effects of catecholamines (i.e. increases sympathetic activity)

·       Potentiates brain development

·       Thickens endometrium in females

·       Increases catabolism of proteins and carbohydrates.

 

50% discount for students on Physiology exam guides e-books

 

50% discount for students on Physiology exam guides e-books

Use Code 6HDXXAA on checkout.

visit the link below or copy paste in your browser-

https://physiologytc.gumroad.com/l/qnerjg

Melatonin

 

Melatonin

Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. In 1917, Carey Pratt McCord and Floyd P. Allen found that feeding extracts from the pineal glands of cows caused the skin of tadpoles to lighten by contracting the dark epidermal melanophores.

The hormone melatonin was isolated from bovine pineal gland extracts in 1958 by Aaron B. Lerner, a dermatology professor, and his team at Yale University. Lerner and his colleagues proposed the name melatonin, derived from the Greek words melas, meaning 'black' or 'dark', and tonos, meaning 'labour', 'colour' or 'suppress' as it was found to lighten skin colour.  Subsequent research in the mid-1970s by Lynch and others demonstrated that melatonin production follows a circadian rhythm in human pineal glands. This compound was later identified as a hormone secreted in the brain during the night, playing a crucial role in regulating the sleep-wake cycle, also known as the circadian rhythm, in human.

Biosynthesis

The biosynthesis of melatonin in animals involves a sequence of enzymatic reactions starting with L-tryptophan, which can be synthesized through the shikimate pathway from chorismate, found in plants, or obtained from protein catabolism. The initial step in the melatonin biosynthesis pathway is the hydroxylation of L-tryptophan's indole ring by the enzyme tryptophan hydroxylase, resulting in the formation of 5-hydroxytryptophan (5-HTP). Subsequently, 5-HTP undergoes decarboxylation, facilitated by pyridoxal phosphate and the enzyme 5-hydroxytryptophan decarboxylase, yielding serotonin.

Serotonin, itself an essential neurotransmitter, is further converted into N-acetylserotonin by the action of serotonin N-acetyltransferase, using acetyl-CoA. The final step in the pathway involves the methylation of N-acetylserotonin's hydroxyl group by hydroxyindole O-methyltransferase, with S-adenosyl methionine as the methyl donor, to produce melatonin.

Regulation of secretion

In human, the secretion of melatonin is regulated through the activation of the beta-1 adrenergic receptor by the hormone norepinephrine. Norepinephrine increases the concentration of intracellular cAMP via beta-adrenergic receptors, which in turn activates the cAMP-dependent protein kinase A (PKA). PKA then phosphorylates arylalkylamine N-acetyltransferase (AANAT), the penultimate enzyme in the melatonin synthesis pathway. When exposed to daylight, noradrenergic stimulation ceases, leading to the immediate degradation of the protein by proteasomal proteolysis.

Blue light, especially within the 460–480 nm range, inhibits the biosynthesis of melatonin, with the degree of suppression being directly proportional to the intensity and duration of light exposure. Historically, humans in temperate climates experienced limited exposure to blue daylight during winter months, primarily receiving light from sources that emitted predominantly yellow light, such as fires. The incandescent light bulbs used extensively throughout the 20th century emitted relatively low levels of blue light. It has been found that light containing only wavelengths greater than 530 nm does not suppress melatonin under bright-light conditions. The use of glasses that block blue light in the hours preceding bedtime can mitigate melatonin suppression. Additionally, wearing blue-blocking goggles during the last hours before bedtime is recommended for individuals needing to adjust to an earlier bedtime since melatonin facilitates the onset of sleep.

Metabolism

Melatonin is metabolized in liver by liver enzymes, with an elimination half-life ranging from 20 to 50 minutes. The primary metabolic pathway transforms melatonin into 6-hydroxymelatonin, which is then conjugated with sulfate and excreted in urine as a waste product.

Measurement

For both research and clinical purposes, melatonin levels in humans can be determined through saliva or blood plasma analysis.

Physiological functions

Circadian rhythm

In human, melatonin is critical for the regulation of sleep–wake cycles, or circadian rhythms. The establishment of regular melatonin levels in human infants occurs around the third month after birth, with peak concentrations observed between midnight and 8:00 am. It has been documented that melatonin production diminishes as a person ages. Additionally, a shift in the timing of melatonin secretion is observed during adolescence, resulting in delayed sleep and wake times, increasing their risk for delayed sleep phase disorder during this period.

Antioxidant Properties

The antioxidant properties of melatonin were first recognized in 1993. In vitro studies reveal that melatonin directly neutralizes various reactive oxygen species, including hydroxyl (OH•), superoxide (O2−•), and reactive nitrogen species such as nitric oxide (NO•).

Melatonin's concentration in the mitochondrial matrix is significantly higher than that found in the blood plasma, emphasizing its role not only in direct free radical scavenging but also in modulating the expression of antioxidant enzymes and maintaining mitochondrial integrity. This multifaceted role shows the physiological significance of melatonin as a mitochondrial antioxidant, a notion supported by numerous scholars.

Furthermore, the interaction of melatonin with reactive oxygen and nitrogen species results in the formation of metabolites capable of reducing free radicals. These metabolites, including cyclic 3-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), and N1-acetyl-5-methoxykynuramine (AMK), contribute to the broader antioxidative effects of melatonin through further redox reactions with free radicals.

Immune system

Melatonin's interaction with the immune system is recognized, yet the specifics of these interactions remain inadequately defined. An anti-inflammatory effect appears to be the most significant. The efficacy of melatonin in disease treatment has been the subject of limited trials, with most available data deriving from small-scale, preliminary studies. It is posited that any beneficial immunological impact is attributable to melatonin's action on high-affinity receptors (MT1 and MT2), which are present on immunocompetent cells. Preclinical investigations suggest that melatonin may augment cytokine production and promote the expansion of T cells, thereby potentially mitigating acquired immunodeficiencies.

Weight regulation

Melatonin's potential to regulate weight gain is posited to involve its inhibitory effect on leptin, a hormone that serves as a long-term indicator of the body's energy status.

Use as a medication and supplement

As a medicine it is used in following conditions under medical supervision-

1.      Insomnia- in persons above 55 years

2.      Circadian rhythm sleep disorders like- delayed sleep phase syndrome and to reduce jet lag syndrome

3.     REM sleep behavior disorders- like Parkinson's disease and dementia with Lewy bodies.

4.       Dementia- melatonin may improve sleep in minimal cognitive impairment only in cases of dementia.

Diabetes Guidelines 2026

 

Diabetes Guidelines 2026: What's New in Evidence-Based Care

The American Diabetes Association (ADA) has released its highly anticipated "Standards of Care in Diabetes—2026," marking another year of comprehensive updates to the gold standard in diabetes management. Published in January 2026, these guidelines reflect the latest scientific research and clinical evidence designed to improve outcomes for the millions of people living with diabetes and prediabetes worldwide.

Overview of the 2026 Standards of Care

The ADA's Standards of Care represents significant advancement in the delivery of evidence-based, person-centered care, synthesizing the latest scientific research with practical clinical strategies to equip healthcare professionals with tools necessary to provide optimal care for individuals living with diabetes. The guidelines include strategies for diagnosing and treating diabetes in children, adolescents, and adults, methods to prevent or delay diabetes and its associated comorbidities like obesity, and care recommendations to enhance health outcomes.

Key Resources Available

The 2026 Standards of Care are accessible through multiple channels to ensure clinicians and patients can access current information:

• Full guidelines published online and in Diabetes Care journal
• Convenient mobile apps for iOS and Android with interactive tables and algorithms
• Abridged version for primary care professionals (coming spring 2026)
• Comprehensive slide decks and webinars with continuing education credits
• Quick-reference pocket charts

Major Changes in 2026: A Technology-Forward Approach

Expanded Diabetes Technology Recommendations

One of the most significant changes in the 2026 guidelines is the emphasis on earlier access to advanced diabetes technologies.

Continuous Glucose Monitoring (CGM)

The 2026 updates include expanded recommendations for technology use, such as continuous glucose monitoring (CGM) and automated insulin delivery (AID). The updated guidelines now recommend CGM use at the onset of diabetes for those using insulin and for anyone at risk of hypoglycemia or who would benefit from CGM in supporting blood sugar management.

CGM is encouraged at diagnosis with earlier access, and over-the-counter CGMs are acknowledged as useful for people with prediabetes or type 2 diabetes wanting lifestyle feedback. Additionally, in people with diabetes on insulin therapy, CGM devices should be used as close to daily as possible for maximal benefit, with uninterrupted access to supplies to minimize gaps in CGM.

Automated Insulin Delivery (AID)

A major change in 2026 is the recommendation of AID systems as the preferred insulin delivery system for all people with type 1 diabetes and children and adults with type 2 diabetes who use insulin. Notably, the updated advice specifies that there should be no requirement of C-peptide level, presence of islet autoantibodies or duration of insulin treatment before initiation of insulin pumps or automated systems. This removes previous barriers to accessing these life-changing technologies.

The ADA Standards recognize open-source AID systems—such as AndroidAPS, Loop, iAPS, and Trio—as part of mainstream diabetes care, with an encouragement for clinicians to engage rather than avoid patient-driven technology.

Revolutionary GLP-1 Guidance for Type 1 Diabetes

For the first time, the 2026 Standards support GLP-1s and similar drugs for people with type 1 diabetes. This represents a paradigm shift in type 1 diabetes management. A major change in the 2026 edition is the new support of GLP-1 and similar drugs for use in adults with type 1 diabetes with a body mass index (BMI) greater than 30 (27.5 for Asian Americans).

For type 2 diabetes patients with comorbidities, the guidelines also suggest broader access for GLP-1-based medicines because of their benefits beyond glucose management and weight. Additionally, GLP-1 medications are now recommended as the initial therapy for adults with type 2 diabetes and liver fibrosis and MASLD (metabolic dysfunction-associated steatotic liver disease).

Updated Management Strategies for Comorbidities

Liver Disease (MASLD and MASH)

The 2026 guidelines place increased emphasis on managing metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). The guidelines now address liver disease, including MASH (metabolic dysfunction-associated steatohepatitis), an advanced form of liver disease marked by excess fat in the liver, which is common in type 2 diabetes and has implications for heart and kidney health.

Kidney Disease Management

The guidelines recommend that individuals with kidney disease may need testing more often, in consultation with their healthcare provider. The guidelines reaffirm blood pressure goals, recommending levels below 130/80 mmHg for most people with diabetes, and aiming for even lower systolic blood pressure when it can be done safely.

Weight Loss and Obesity Management

A more aggressive approach to weight management is now recommended. Lifestyle plans involving diet, physical activity, and other health behaviors should aim for a weight loss target of 5–7% of baseline body weight, demonstrating increased emphasis on obesity as a primary target for intervention.

Nutrition Guidelines: Moving Beyond High-Carbohydrate Diets

The 2026 Standards represent a significant shift in nutritional guidance. Rather than recommending small, frequent high-carbohydrate meals, the new guidelines propose a range of potential eating patterns that fall under the broader umbrella of low-carbohydrate/lower starch diets, including the Mediterranean, plant-based, and the Dietary Approaches to Stop Hypertension (DASH) diet as options that can support patients' overall health.

Mediterranean and low-carbohydrate diets are specified as having the best evidence for preventing or delaying onset of type 2 diabetes in high-risk individuals.

Physical Activity Recommendations

The guidelines maintain emphasis on regular physical activity for blood glucose management and overall health. For adults with diabetes, the recommendation is to engage in 150 minutes or more of moderate- to vigorous-intensity aerobic activity per week, spread over at least 3 days/week, with no more than 2 consecutive days without activity. Additionally, prolonged sitting should be interrupted at least every 30 minutes for blood glucose and other benefits.

Screening and Behavioral Health Support

The 2026 Standards place greater emphasis on mental health support and screening, recognizing the psychological burden of diabetes management. The guidelines include guidance on behavioral health screening and referral for concerns such as diabetes distress and anxiety, with recommendations for annual screening for anxiety and fear of hypoglycemia in those at risk.

Person-Centered Care and Team-Based Approach

A foundational principle throughout the 2026 Standards is person-centered care. The Standards of Care stress the importance of coordinated interprofessional teams, which include physicians, diabetes educators, dietitians, pharmacists, and mental health counselors, in guiding diabetes patient care.

The guidelines emphasize that care systems should facilitate in-person and virtual team-based care, include those knowledgeable and experienced in diabetes management as part of the team, and utilize patient registries, decision support tools, proactive care planning, and community involvement to meet needs of individuals with diabetes.

Implementation and Accessibility

Digital Tools and AI Support

To support clinicians in implementing these guidelines, the ADA partnered with the artificial intelligence initiative OpenEvidence to create a tool that will allow physicians to ask the Standards of Care specific questions and receive clinically backed answers, available free of charge for healthcare professionals registered with the ADA.

Living Guidelines Model

The 2026 Standards operate as "living guidelines," meaning they are continuously updated throughout the year as new evidence emerges. The online version, abridged guidelines, and all related materials will be updated in real time throughout the year to reflect the latest evidence and regulatory changes.

Global Endorsements and Professional Recognition

The 2026 Standards have received endorsements from numerous professional organizations, reflecting their comprehensive and evidence-based nature. For the eighth consecutive year, section 10 on "Cardiovascular Disease and Risk Management," received endorsement from the American College of Cardiology. For the second consecutive year, section 13 on "Older Adults" received endorsement from the American Geriatrics Society. For the first time, section 11 on "Chronic Kidney Disease and Risk Management" and section 14 on "Children and Adolescents" received endorsement from the National Kidney Foundation and the International Society for Pediatric and Adolescent Diabetes, respectively.

Implications for Healthcare Practice

The 2026 Standards represent a shift toward:

Earlier intervention: Technologies and therapies are now recommended at diagnosis rather than as last resorts.

Broader access: Removed prerequisites for advanced therapies ensure more patients can benefit from newer treatments.

Personalization: Guidelines emphasize individualized approaches based on patient values, preferences, and comorbidities.

Technology integration: Recognition that patient-driven innovations are part of mainstream care.

Holistic health: Greater attention to mental health, lifestyle, and comorbidity management alongside glucose control.

Conclusion

The 2026 "Standards of Care in Diabetes" represents significant advancement in the delivery of evidence-based, person-centered care, equipping healthcare professionals with the tools necessary to provide optimal care for individuals living with diabetes. With emphasis on technology adoption, broader GLP-1 use, personalized nutrition, and team-based care, these guidelines mark a significant evolution in diabetes management.

Healthcare providers and patients should familiarize themselves with these updated recommendations through the various resources available, from the full text to mobile apps and quick-reference guides. The goal remains consistent across all changes: to improve health outcomes and quality of life for the millions of people affected by diabetes.

---

References

1. American Diabetes Association. "Standards of Care in Diabetes—2026." Diabetes Care, January 2026. https://diabetes.org/newsroom/press-releases/american-diabetes-association-releases-standards-care-diabetes-2026

2. American Diabetes Association Professional Practice Committee for Diabetes. "Summary of Revisions: Standards of Care in Diabetes—2026." Diabetes Care, Vol. 49, Supplement 1, January 2026. https://diabetesjournals.org/care/article/49/Supplement_1/S6/163930/

3. Professional Diabetes Association. "Standards of Care in Diabetes - ADA Clinical Guidelines." https://professional.diabetes.org/standards-of-care

4. DiaTribe. "Your Guide to the 2026 ADA Standards of Care." December 2025. https://diatribe.org/diabetes-management/your-guide-2026-ada-standards-care

5. DiabetesOnTheNet. "Factsheet - 2026 ADA Standards." https://diabetesonthenet.com/diabetes-primary-care/factsheet-2026-ada-standards/

6. MedCentral. "The 2026 ADA Standards of Care in Diabetes Embrace Technology to Support Holistic Care." December 2025. https://www.medcentral.com/endocrinology/diabetes/the-2026-ada-standards-of-care-in-diabetes-embrace-technology-to-support-holistic-care

7. Guideline Central. "2026 ADA Diabetes Standards of Care Guideline — New Recommendations." December 2025. https://www.guidelinecentral.com/insights/dec-2025-ada-diabetesstandardsofcare-guideline-spotlight/

8. Diabetotech. "Key Updates: ADA 2026 Diabetes Technology Guidelines." https://www.diabetotech.com/blog/key-updates-ada-2026-diabetes-technology-guidelines

9. ACP Diabetes Monthly. "ADA's Standards of Care for 2026 released." December 2025. https://www.acpjournals.org/doi/10.7326/acpd-20251212_1

---

Disclaimer: This blog post is for informational purposes only and should not be considered medical advice. Individuals should consult with their healthcare provider for personalized diabetes management recommendations.

Last Updated: January 2026

How to Prepare for Medical Entrance Exams: A Complete Roadmap for Success

 

 

How to Prepare for Medical Entrance Exams: A Complete Roadmap for Success

Preparing for a medical entrance examination is not merely about memorizing textbooks or solving endless question papers. It is a long-term intellectual, emotional, and psychological journey that demands discipline, consistency, strategic planning, and resilience. Medical entrance exams—such as NEET (India), MCAT (USA), or similar national-level tests in other countries—are designed to assess not only knowledge but also conceptual clarity, analytical ability, and stamina.

This article presents a step-by-step, realistic, and student-centered roadmap to help aspirants prepare effectively and sustainably for medical entrance exams.

---

1. Understand the Nature of the Exam

Before opening a single book, you must clearly understand:

• Syllabus
• Exam pattern
• Number of questions
• Marking scheme
• Time duration
• Weightage of topics

Why This Matters

Many students waste precious months studying irrelevant material or overemphasizing low-weightage topics. A precise understanding of the syllabus ensures focused preparation.

Practical Steps

• Download the official syllabus from the exam authority.
• Break the syllabus into subject-wise and chapter-wise lists.
• Mark:
• High-weightage topics
• Medium-weightage topics
• Low-weightage topics

This classification will later guide your time allocation.

---

2. Build a Strong Conceptual Foundation

Medical entrance exams test conceptual understanding, not rote memorization.

Subject-Wise Focus

Biology

• Understand processes and mechanisms.
• Focus on NCERT (or official base text).
• Make diagrams and flowcharts.

Physics

• Master fundamental laws and formulas.
• Understand derivations and applications.
• Practice numerical problems daily.

Chemistry

• Physical Chemistry: numerical practice
• Organic Chemistry: reaction mechanisms
• Inorganic Chemistry: periodic trends, exceptions, and properties

Golden Rule

If you cannot explain a concept in simple words, you have not truly understood it.

---

3. Choose the Right Study Material

Using too many books creates confusion.

Ideal Resources

• One primary textbook per subject
• One question bank
• One mock test series

Quality matters more than quantity.

Recommended Approach

• Thoroughly master one standard book instead of superficially reading five.

---

4. Create a Realistic Study Plan

A good timetable is flexible, achievable, and personalized.

Daily Structure Example

• Morning: New concepts
• Afternoon: Practice questions
• Evening: Revision
• Night: Light study or formula review

Weekly Structure

• 5 days: Learning + Practice
• 1 day: Revision
• 1 day: Full-length mock test

Important Principle

Consistency beats intensity.

Studying 6 hours daily for a year is better than 14 hours daily for two months.

---

5. Master Active Learning Techniques

Passive reading is ineffective.

Effective Techniques

• Self-questioning
• Teaching others
• Flashcards
• Mind maps
• Summarizing in your own words

Example

Instead of reading respiration:

Ask:

• Why is oxygen necessary?
• What happens if oxygen is absent?
• How does ATP generation change?

---

6. Practice Questions Daily

Practice transforms knowledge into performance.

Types of Questions

• Conceptual
• Numerical
• Assertion-Reason
• Case-based

Suggested Ratio

For every 1 hour of study → 1 hour of practice

Error Notebook

Maintain a notebook for:

• Mistakes
• Weak concepts
• Tricky questions

Revise this notebook weekly.

---

7. Regular Revision Strategy

Without revision, forgetting is inevitable.

The 3-Level Revision Rule

1.    Same day revision

2.    Weekly revision

3.    Monthly revision

Tools for Revision

• Short notes
• Formula sheets
• Flashcards

Revision converts short-term memory into long-term memory.

---

8. Take Mock Tests Seriously

Mock tests simulate the real exam environment.

Benefits

• Time management
• Stress handling
• Identifying weak areas

After Every Mock Test

• Analyze mistakes
• Categorize errors:
• Conceptual
• Silly mistakes
• Time pressure

Improvement happens in analysis, not just in attempting tests.

---

9. Strengthen Time Management

In medical entrance exams, speed is crucial.

Tips

• Do not get stuck on one question.
• Follow a round system:
• Round 1: Easy questions
• Round 2: Moderate
• Round 3: Difficult

Practice solving questions within time limits.

---

10. Develop Exam Temperament

Many capable students fail due to panic.

Build Mental Toughness By:

• Taking frequent mock tests
• Practicing meditation or breathing exercises
• Visualizing success

Confidence comes from preparation.

---

11. Take Care of Physical Health

Your brain cannot function optimally in a weak body.

Essentials

• 7–8 hours of sleep
• Balanced diet
• Adequate hydration
• Light exercise or walking

Avoid excessive caffeine and junk food.

---

12. Protect Your Mental Health

Long preparation periods can cause anxiety, burnout, and self-doubt.

Healthy Practices

• Take short breaks
• Limit social media
• Talk to supportive people
• Avoid comparing yourself with others

Everyone’s journey is different.

---

13. Role of Parents and Teachers

Supportive guidance enhances success.

Parents should:

• Encourage, not pressure
• Celebrate effort, not only results

Teachers should:

• Clarify doubts patiently
• Provide structured feedback

---

14. Avoid Common Mistakes

• Starting too many resources
• Ignoring NCERT/basic textbooks
• Skipping revision
• Studying without practice
• Comparing with toppers

Awareness of mistakes prevents repetition.

---

15. Last 2–3 Months Strategy

Focus On

• Revision
• Mock tests
• Weak areas

Avoid

• New books
• Major changes in routine
• Panic-driven decisions

Stability is key.

---

16. One-Month Before Exam

• Daily revision
• Light practice
• Sleep well
• Maintain calmness

Do not try to “learn everything.” Strengthen what you already know.

---

17. On Exam Day

• Reach early
• Carry required documents
• Stay calm
• Read questions carefully
• Trust your preparation

---

18. The Right Mindset

Medical entrance preparation is a marathon, not a sprint.

You will face:

• Bad days
• Low scores
• Self-doubt

These do not define your potential.

What defines you is:

Consistency + Discipline + Persistence

---

Conclusion

Preparing for medical entrance exams is a life-shaping experience. Beyond securing a seat in medical college, it teaches patience, discipline, resilience, and self-belief. Success does not belong only to geniuses; it belongs to those who show up every day and do the work, even when motivation fades.

If you remain consistent, revise regularly, practice wisely, and take care of your mental and physical health, success will eventually follow.

Dream of becoming a doctor, but work like one today.

---