The Role Of Leptin In Diabetes: Metabolic Effects
, Volume 59, Issue5 , pp 928932 | Cite as The role of leptin in diabetes: metabolic effects While it is well established that the adiposity hormone leptin plays a key role in the regulation of energy homeostasis, growing evidence suggests that leptin is also critical for glycaemic control. In this review we examine the role of the brain in the glucose-lowering actions of leptin and the potential mediators responsible for driving hyperglycaemia in states of uncontrolled insulin-deficient diabetes (uDM). These considerations highlight the possibility of targeting leptin-sensitive pathways as a therapeutic option for the treatment of diabetes. This review summarises a presentation given at the Is leptin coming back? symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Christoffer Clemmensen and colleagues, DOI: 10.1007/s00125-016-3906-7 , and by Gerald Shulman and colleagues, DOI: 10.1007/s00125-016-3909-4 ) and an overview by the Session Chair, Ulf Smith (DOI: 10.1007/s00125-016-3894-7 ). BrainCorticosteroneDiabetesGlucagonHepatic glucose productionLeptinReview Diabetes is increasing steadily all over the world. The International Diabetes Federation estimates that more than 382 million people have diabetes globally and this number is expected to exceed 590 million by 2035 [ 1 ]. This is a serious health concern since people with diabetes are vulnerable to both short- and long-term complications, including cardiovascular and renal disease, blindness and amputation [ 2 ]. Given the continued prevalence and incidence of diabetes and its considerable health burden, a better understanding of its pathogenesis is required to facilitate the development of new strategies for its treatment. Ever since its discov Continue reading >>
How Leptin, The Satiety Hormone, Reverses Diabetes
How leptin, the satiety hormone, reverses diabetes Treatment with leptin, the hormone associated with fullness or satiety, reverses hyperglycemia in animals models of poorly controlled type 1 (T1D) and type 2 (T2D) diabetes by suppressing the neuroendocrine pathways that cause blood glucose levels to soar, a Yale-led team of researchers has found. The study appears in the Advance Online Publication of Nature Medicine. The leptin hormone regulates metabolism, appetite, and body weight. The researchers discovered that, in a fasting state, rats with poorly controlled T1D and T2D diabetes had lower plasma insulin and leptin concentrations and large increases in concentrations of plasma corticosterone a stress hormone made in the adrenal glands that raises levels of blood glucose. The researchers then found that normalizing plasma leptin concentrations in the T1D rats with a leptin infusion resulted in marked reductions in plasma glucose concentrations, which could mostly be attributed to reduction in rates of liver conversion of lactate and amino acids into glucose. The question was why this happened. The teams data revealed that leptin normalized plasma corticosterone and plasma glucose concentrations by inhibiting the hypothalamic-pituitary-adrenal axis, a critical neuroendocrine pathway consisting of three major glands that regulate many body processes, including reactions to stress, energy storage, and energy utilization. Researchers believe their finding about leptin may lead to development of new types of therapies to reduce and reverse uncontrolled hyperglycemia in patients with type 1 and type 2 diabetes. Previous studies by our group found that leptin replacement therapy reversed diabetes and insulin resistance in patients with severe lipodystophy a loss of fatty Continue reading >>
Diabetes And Leptin Connection
Read our free report Chronic Pain Manifesto and resolve your health problems Our new website is currently launching ~ Please report any errors/anomalies by phone 1-866-543-3388 ~ Thank You "Whether you think you can or you think you can't, you're right." -Henry Ford Twenty years from now you will be more disappointed by the things that you didn't do than by the ones you did do. Explore. Dream. Discover. H. Jackson Brown Jr. Leptin is a a protein produced by fat cells and is involved in regulating food intake and fat storage in the body. This article explains leptin's function in relation to insulin resistance. Normally, leptin's function is to reduce appetite and induce fat burning (among many other functions). That is what high leptin signaling in a brain would do. Low leptin (in the brain) is an indication to eat more and store more fat (to successfully reproduce and to live long enough to do so). However, elevated leptin in a fasting blood sample indicates leptin resistance and likely low leptin signaling to some parts of the brain while other parts of the brain get the full high signal. In other words, some of the brain only hears a whisper while other parts (of the brain and periphery) get screamed at. Low leptin signaling getting through to the appetite center of the brain induces the brain to want to make the rest of your body hungry and will alter physiologic functions so as to make you store more fat. Ultimately, and finally, increasing fat stores should manufacture more leptin to overcome the resistance but, in the meantime, one continues to get fat and often ultimately obese. This is similar to insulin resistance, when high fasting insulin indicates low activity in some parts of your body and a disruption in insulin signaling that is being compensated for by Continue reading >>
Leptin And Diabetes Are You Leptin Resistant?
Leptin and Diabetes Are You Leptin Resistant? We know insulin resistance contributes to Type 2 diabetes. But resistance to another hormone called leptin also contributes big time. Fortunately, we may be able to turn down both kinds of resistance. Leptin helps regulate body fat, in part by telling the brain what level of fat is in the body and how that level is changing. When fat stores are sufficient, it lets the brain know, Were full. We have enough food now. So stop eating. Some Indian scientists put it in more technical terms : The net action of leptin is to inhibit appetite, stimulate thermogenesis [heat production], [burn up fatty acids], decrease glucose, and reduce body weight and fat. Those are good things for most of us. We want that. But many people, especially fat people, are leptin resistant. Talking to the UK newspaper Daily Mail, anti-sugar crusader Robert Lustig, MD, said, This means thebrainno longer reads the signals saying the body is full, but instead assumes it is starving no matter how much food you continue to eat. So leptin resistance (LR) contributes to fatness in much the same way that insulin resistance (IR) contributes to Type 2 diabetes. In fact, the two frequently go together. Not always as we know, most fat people dont have diabetes, and many people with Type 2 are thin. But a huge number of people have both types of resistance, which is why fat people are more likely to get diabetes, and diabetes gets wrongly blamed on fat. In fact, Dr. Lustig believes insulin resistance triggers LR . Insulin blocks leptins fullness signals in the brain. His studies have found that lowering insulin levels stops cravings and helps people get control of their food consumption, presumably because leptin is working again. Scientists used to think increasing l Continue reading >>
Leptin, Diabetes, And The Brain
Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA, USA Corresponding Author: Dr. Gregory J. Morton, UW Medicine at South Lake Union, 850 Republican St, Box 358055, Seattle, WA 98195, USA. E-mail: ude.notgnihsaw.u@notromjg Author information Copyright and License information Disclaimer Copyright : Indian Journal of Endocrinology and Metabolism This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC. Diabetes is a major worldwide problem. Despite some progress in the development of new antidiabetic agents, the ability to maintain tight glycemic control in order to prevent renal, retinal, and neuropathic complications of diabetes without adverse complications still remains a challenge. Recent evidence suggests, however, that in addition to playing a key role in the regulation of energy homeostasis, the adiposity hormone leptin also plays an important role in the control of glucose metabolism via its actions in the brain. This review examines the role of leptin action in the central nervous system and the mechanisms whereby leptin mediates its effects to regulate glucose metabolism. These findings suggest that defects or dysfunction in leptin signaling may contribute to the etiology of diabetes and raise the possibility that either leptin or downstream targets of leptin may have therapeutic potential for the treatment of diabetes. Keywords: Brain, diabetes, glucose, insulin, leptin The incidence and prevalence of diabetes is increasing globally.[ 1 ] More than 250 mil Continue reading >>
Diabetes Information Symptoms, Causes And Prevention
The Risks of Treating Diabetes with Drugs Are FAR Worse than the Disease There is a staggering amount of misinformation on diabetes, a growing epidemic that afflicts more than 29 million people in the United States today. The sad truth is this: it could be your very OWN physician perpetuating this misinformation Most diabetics find themselves in a black hole of helplessness, clueless about how to reverse their condition. The bigger concern is that more than half of those with type 2 diabetes are NOT even aware they have diabetes and 90 percent of those who have a condition known as prediabetes arent aware of their circumstances, either. The latest diabetes statistics 1 echo an increase in diabetes cases, both diagnosed and undiagnosed. By some estimates, diabetes has increased more than 700 percent in the last 50 years! At least 29 million Americans are diagnosed with type 2 diabetes, and another 86 million are prediabetic . Whats hidden behind this medical smokescreen is that type 2 diabetes is completely preventable. The cure lies in a true understanding of the underlying cause (which is impaired insulin and leptin sensitivity) and implementing simple, inexpensive lifestyle adjustments that spell phenomenal benefits to your health. Also known as diabetes mellitus, type 1 diabetes is a chronic health condition traditionally characterized by elevated levels of glucose in your blood, often simply called high blood sugar. Type 1 diabetes dubbed juvenile onset diabetes is the relatively uncommon type, affecting only about 1 in 250 Americans. Occurring in individuals younger than age 20, it has no known cure. Whats most concerning about juvenile diabetes is that, these numbers have been going up steadily right along with type 2 diabetes: for non-Hispanic white youths ages Continue reading >>
The Potential Of Leptin For Treating Diabetes And Its Mechanism Of Action
The Potential of Leptin for Treating Diabetes and Its Mechanism of Action We are experimenting with display styles that make it easier to read articles in PMC. The ePub format uses eBook readers, which have several "ease of reading" features already built in. The ePub format is best viewed in the iBooks reader. You may notice problems with the display of certain parts of an article in other eReaders. Generating an ePub file may take a long time, please be patient. The Potential of Leptin for Treating Diabetes and Its Mechanism of Action Following the discovery of leptin in 1994, major research efforts have brought us much closer to a fuller understanding of the cellular and molecular mechanisms underlying the biological effects of the hormone. Interestingly, leptin exerts potent anti-diabetic actions that are independent of its effects on body weight and food intake. In particular, leptin can correct diabetes in animal models of either diabetes mellitus type 1 (T1DM) or type 2 (T2DM). In addition, long-term leptin-replacement therapy is well tolerated and dramatically improves glycemic control, insulin sensitivity, and plasma triglycerides in patients with severe insulin resistance due to lipodystrophy. Together, these results have spurred enthusiasm for the use of leptin therapy to treat humans suffering from diabetes mellitus. Here, we review current understandings of these glucoregulatory functions of leptin, with particular emphasis on its central mechanisms of action, lessons from clinical studies and discuss possible therapeutic applications of leptin in the treatment of T1DM and T2DM. Even with the improved anti-diabetic drugs, enhanced glycemia monitor systems, easier patient-to-physician accessibility, people who have type 2 diabetes mellitus (T2DM; an illness Continue reading >>
The Role Of Leptin In Diabetes: Metabolic Effects.
The role of leptin in diabetes: metabolic effects. Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington at South Lake Union, 850 Republican St., N335, Box 358055, Seattle, WA, 98195, USA. Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington at South Lake Union, 850 Republican St., N335, Box 358055, Seattle, WA, 98195, USA. [email protected]. Diabetologia. 2016 May;59(5):928-32. doi: 10.1007/s00125-016-3898-3. Epub 2016 Mar 11. While it is well established that the adiposity hormone leptin plays a key role in the regulation of energy homeostasis, growing evidence suggests that leptin is also critical for glycaemic control. In this review we examine the role of the brain in the glucose-lowering actions of leptin and the potential mediators responsible for driving hyperglycaemia in states of uncontrolled insulin-deficient diabetes (uDM). These considerations highlight the possibility of targeting leptin-sensitive pathways as a therapeutic option for the treatment of diabetes. This review summarises a presentation given at the 'Is leptin coming back?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Christoffer Clemmensen and colleagues, DOI: 10.1007/s00125-016-3906-7 , and by Gerald Shulman and colleagues, DOI: 10.1007/s00125-016-3909-4 ) and an overview by the Session Chair, Ulf Smith (DOI: 10.1007/s00125-016-3894-7 ). Continue reading >>
Insulin, Leptin, And Blood Sugar – Why Diabetic Medication Fails
This Week's Health Podcast > Type 2 diabetes is a difficult metabolic problem. It is a national embarrassment that so many of our young people are becoming type 2 diabetic. It is a national disgrace that millions of type 2 diabetic patients are being injured with commonly used diabetic medications that are known to make their metabolic situation worse. An overwhelming body of science demonstrates that insulin resistance leads to obesity and vice versa. Once this problem sets in, a person is on a path of ever worsening metabolic control as diabetes related issues, cholesterol problems, and heart disease risk factors pile up. If nothing is done, very poor health, and early death are certain. The Big Pharma blood sugar remedies, however, turn out to be really bad for health – they actually complicate rather than improve the patient's health. Even when the drugs aren't directly damaging in a major way, they fail to address the actual reasons for diabetes and typically have the net result of making the factors that cause diabetes worse. I know that may seem hard to believe, but it is true, and I will explain it shortly. On December 17, 2008 the New England Journal of Medicine1 put the nail in the coffin on another dismal year for the theory of drugs to treat disease, reporting that aggressive use of blood sugar lowering medication to prevent heart disease was a complete failure. Its not that lowering blood sugar in this patient population didn't do anything; it made the patients heavier and more hypoglycemic. This newer study followed equally dismal results from the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes), which earlier in 2008 found a 22 percent increased rate of death in diabetic patients who were aggressively treated with medications. Some of th Continue reading >>
Fat Hormone Leptin May Control Diabetes
Leptin May Control Gene in Liver That Reverses Diabetes Jan. 5, 2010 -- The so-called fat hormone leptin may play a key role in controlling and potentially reversing diabetes , a role that has nothing to do with its link to weight loss . The hormone leptin has been nicknamed the fat hormone after numerous studies have shown it promotes weight loss, which in turn has a beneficial effect on diabetes control. But a new study suggests that small amounts of leptin -- too small to promote weight loss -- are enough to control the activity of a gene known as IGFBP2 in the liver that improves diabetes in animals and may have the same effect in people. "It was surprising to me how potent leptin was in treating diabetes," researcher Jeffrey Friedman of Rockefeller University says in a news release. "It had a highly significant impact at plasma levels that were undetectable." Researchers say the findings confirm that leptins beneficial effects on diabetes control are independent of the hormones weight loss effects. Previous studies have shown that treatment with hormone leptin corrects high blood sugar and insulin levels in mice and people with low levels of the hormone. To examine leptins effects on diabetes control, researchers first identified the lowest dose of leptin that improved insulin resistance and diabetes without causing animals to eat less or lose weight . They then looked at the effects of these low doses of leptin on activity of genes in the animals livers. The results, published in Cell Metabolism , showed leptin increased IGFBP2 in obese and diabetic mice and reversed their diabetes. Researchers also found mice treated with the fat hormone responded to insulin three times better than untreated mice. Further studies will be needed to determine if leptin treatment i Continue reading >>
Leptin Resistance: The Other Hormone Important For Managing Diabetes | Everyday Health
Eating a Mediterranean-style diet with lean protein, whole grains, and healthy fats can help increase leptin sensitivity. When most people think of diabetes and hormones, insulin which controls blood sugar levels by ferrying glucose to cells for energy is usually the first that springs to mind. But there are many hormones at play when it comes to blood sugar levels and weight, and anyone living with diabetes or prediabetes should consider them all when striving to better manage their symptoms. Key among these is leptin, a hormone produced by fat cells that helps the body regulate energy by telling the brain its had enough to eat, according to a review published in December 2012 in the Indian Journal of Endocrinology and Metabolism . Leptins action is to inhibit appetite, to stimulate the burning up of fatty acids, to decrease glucose, and to reduce overall body fat and weight, says VandanaSheth, RDN, CDE , a spokesperson for the Academy of Nutrition and Dietetics. The problem, Sheth explains, is, just like insulin resistance whereby cells are resistant to insulin, leading glucose to accumulate in the blood people can develop leptin resistance, an effect that can further complicate their diabetes management . When this occurs, Sheth says, People can gain weight, have increased body fat, and, even though there are adequate fat stores, their brains are getting the signal that they are hungry, so they eat more. It's a vicious cycle. Unfortunately, just adding more leptin, as people with diabetes often do with insulin injections , cant fix this problem because the issue isnt always how much leptin is in the body, but whether the body is able to process it efficiently. In fact, for people without diabetes, or for those who have been diagnosed with prediabetes, leptin resista Continue reading >>
A Review Of The Leptin Hormone And The Association With Obesity And Diabetes Mellitus
Received Date: February 06, 2017; Accepted Date: March 01, 2017; Published Date: March 08, 2017 Citation: Facey A, Dilworth L, Irving R (2017) A Review of the Leptin Hormone and the Association with Obesity and Diabetes Mellitus. JDiabetes Metab 8:727. doi:10.4172/2155-6156.1000727 Copyright: 2017 Facey A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Leptin is a protein hormone that regulates food intake. It is secreted by the adipocytes and contains 167 amino acids. The hormone signals the hypothalamus and is released to reduce the desire for food thereby controlling appetite. Research shows that diet-induced obesity results in leptin resistance, so while the level of leptin may be high, it is ineffective. Leptin is also increased in type 2 diabetes mellitus which is strongly associated with obesity and insulin resistance . While leptin may be elevated in both diabetes and obesity, it is not the cause of either disease. It has been suggested that leptin mediates insulin resistance and as such may be a possible treatment for insulin resistance. Diet induced leptin resistance can be reversed through dietary changes and its administration can be effective in combating insulin resistance. Leptin levels may also decrease with increased exercise. The pathophysiology involving leptin resistance is unclear. More leptin studies are needed as it may be an unexplored treatment for diabetes and may be able to provide a more detailed understanding of the disease. Leptin; Obesity; Diabetes; Insulin resistance Leptin which contains 167 amino acids, was discovered in 1994. It isa hormone s Continue reading >>
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Original Article Relationships Between Changes In Leptin And Insulin Resistance Levels In Obese Individuals Following Weight Loss
Abstract Obesity can augment insulin resistance (IR), leading to increased risk of diabetes and heart disease. Leptin, ghrelin, and various fatty acids present in the cell membrane may modulate IR. In this study, we aimed to investigate the impact of weight loss on IR, serum leptin/ghrelin levels, and erythrocyte fatty acids, and studied the associations between changes in these variables. A total of 35 obese (body mass index ≥ 27) adults participated in a weight loss program for 3 months. IR was assessed using homeostasis model assessment for insulin resistance (HOMA-IR). The obese participants had a mean weight loss of 5.6 ± 3.8 kg followed by a 16.7% and 23.3% reduction in HOMA-IR and leptin (p < 0.001) levels, and an 11.3% increase in ghrelin levels (p = 0.005). The level of erythrocyte saturates decreased by 2.8%, while the level of n–3 polyunsaturates increased by 16.8% (all p < 0.05). The changes in leptin levels (−5.63 vs. −1.57 ng/mL) were significantly different (p = 0.004) in those with improved IR (changes in HOMA-IR < 0) than those without improvement (changes in HOMA-IR ≥ 0), though there were no differences in the changes of ghrelin (p = 0.120) and erythrocyte fatty acids (all p > 0.05) levels. After adjusting for age, gender, changes in ghrelin, and body fat, we found a significant correlation between decreases in leptin and less risk of no improvement in HOMA-IR levels [odds ratio (OR) = 0.69, p = 0.039]. In conclusion, a moderate weight reduction in obese participants over a short period significantly improved IR. This weight reduction concomitantly decreased serum leptin, increased ghrelin, and elevated some erythrocyte unsaturates. Only leptin correlated independently with IR improvement upon multivariable logistic regression analysis, whi Continue reading >>
Leptin
Not to be confused with Lectin or Lecithin. Leptin (from Greek λεπτός leptos, "thin"), “the hormone of energy expenditure”,[a] is a hormone predominantly made by adipose cells that helps to regulate energy balance by inhibiting hunger. Leptin is opposed by the actions of the hormone ghrelin, the "hunger hormone". Both hormones act on receptors in the arcuate nucleus of the hypothalamus to regulate appetite to achieve energy homeostasis.[6] In obesity, similar to resistance of insulin in type 2 diabetes, a decreased sensitivity to leptin occurs, resulting in an inability to detect satiety despite high energy stores.[7] 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 multiple sites of synthesis other than fat cells, and the multiple cell types beside hypothalamic cells that have leptin receptors. Many of these additional functions are yet to be defined.[8][9][10][11][12][13] Identification of the gene[edit] In 1949, a non-obese mouse colony being studied at the Jackson Laboratory produced a strain of obese offspring, suggesting that a mutation had occurred in a hormone regulating hunger and energy expenditure. Mice homozygous for the so-called ob mutation (ob/ob) ate voraciously and were massively obese.[14] In the 1960s, a second mutation causing obesity and a similar phenotype was identified by Douglas Coleman, also at the Jackson Laboratory, and was named diabetes (db), as both ob/ob and db/db were obese.[15][16][17] In 1990 Rudolph Leibel and Jeffrey M. Friedman reported mapping of the db gene.[18][19][20] Consistent with Coleman’s and Leibel's hypothesis, several subsequent studies from Leibel's and Friedman’s labs and other groups confirmed that Continue reading >>
Drop In Both Insulin And Leptin Needed For Fat Burning To Occur
Drop in both insulin and leptin needed for fat burning to occur Drop in both insulin and leptin needed for fat burning to occur Ketogenic diet improves metabolic syndrome in multiple ways 18 December 2017 Researchers have found that metabolism moves from using glucose to burning fat when there is a drop in both insulin and leptin levels. The study has been led by Gerald I. Shulman, professor of medicine, cellular and molecular physiology, and physiological chemistry at Yale University. The research could point towards improved understanding of how best to lose weight which could benefit many people with diabetes. Prior to the study, it was known that mammals can switch from burning carbohydrates , like glucose, for energy towards burning fat instead. This allows mammals to get energy without breaking down muscle mass. It was thought that a decrease in insulin levels is all that was needed to help the switch to burning fat occur. However, the new research has identified that a reduction in leptin levels is also needed. Insulin and leptin are both hormones. Insulin works to decrease blood sugar levels by moving glucose out of the blood and into neighbouring cells where it can be used directly as fuel or stored as body fat. A higher level of insulin also prevents fat from being broken down for energy. Leptin is a hormone which is linked to appetite and plays a key role in energy regulation. In their study, the researchers from Yale investigated the rate of carbohydrate and fat metabolism as rats went from a fed to a fasted state. The researchers observed that as the rats fasted, leptin levels decreased and activated a pathway that led to fat burning rather than carbohydrate burning. During fasting, the rats' use of stored glucose went down and sugar levels decreased as a Continue reading >>
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