Leptin: A Potent Inhibitor of Insulin Secretion

Fehmann, Hans-Christoph; Peiser, Christian; Bode, Hans-Peter; Stamm, Matthias; Staats, Petra; Hedetoft, Christoffer; Lang, R.; Göke, Burkhard

doi:10.1016/s0196-9781(97)00135-6

Cited by 93 publications

(77 citation statements)

References 41 publications

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“…A feedback loop possibly exists between leptin and insulin. In perfused rat pancreas, isolated mouse islets [62], and human islets [63], leptin inhibits glucose-induced insulin secretion. Inhibition in human islets, however, required 20 mmol/l glucose; no effect was observed with concentrations of glucose of 10 mmol/l or lower [63,64].…”

Section: Regulation Of Leptin By Insulinmentioning

confidence: 99%

Nutritional regulation of leptin in humans

Coleman

Herrmann

1999

Diabetologia

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OverviewPositional cloning of the defective gene in genetically obese ob/ob mice identified leptin as the long-sought hormone that communicates information about adipocyte metabolism to the brain [1]. Supplying leptin to genetically deficient ob/ob mice increases metabolic rate, body temperature and general activity and decreases food intake, body weight and adiposity [1±4]. Additionally, the importance of leptin to reproduction has been highlighted by the lack of sexual maturation in people who are genetically deficient in leptin [5] or the leptin receptor [6]. Although many of leptin's effects are centrally mediated, there is growing evidence that peripheral leptin receptors mediate leptin's proliferative effects on haemopoietic cells [7] and its anti-lipogenic effects on muscle and pancreatic islets [8,9].Because leptin has a critical role in regulating energy metabolism, adipose stores and body weight, questions have been raised concerning the control of leptin synthesis and secretion and the function of leptin in controlling satiety and food intake. Basal or fasting leptin values are higher in women than men, increase during the course of pregnancy and, in both healthy adults and those with Type II (non-insulindependent) diabetes mellitus, are strongly correlated with per cent body fat or BMI [10,11] and adipose tissue mass [12±15]. Despite these strong correlations, people with similar degrees of adiposity have circulating leptin concentrations that vary considerably. Thus, factors other than adipocyte size and fat content must influence leptin production. Further, the regulation of leptin's diurnal pattern of secretion is still to be explained.In this review we summarize current data, primarily from human studies, that address the nutritional controls on leptin synthesis and secretion and point out fruitful areas for future study. Excellent recent reviews should be consulted for information on the leptin receptor, other aspects of leptin's effects, and the relation of leptin to other hormones that regulate food intake and energy expenditure [16±22]. Leptin regulation by fasting, refeeding and overfeedingFasting and refeeding. During short-term energy restriction, plasma leptin concentrations decrease much more than the amount of weight or adipose tissue lost. For example, lean and obese adults who fasted for 52 to 96 h lost less than 4 % of body weight but the leptin concentrations decreased 54 to 72 % [23±25]. In careful long-term studies of lean and obese people who were either losing weight or maintaining a defined weight loss, leptin concentrations were lower during the period of loss than the period of weight maintenance at the same body composition [26]. After a 4 day fast followed by an additional 6 days of fasting during which an intravenous infusion of 5 % glucose was given, leptin increased 80 % within the first 24 h, even though glucose provided only 338 kcal/day [25]. Although it is possible that the previous 4 day fast confounded these results [27], taken together, these studies suggest that ...

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Section: Regulation Of Leptin By Insulinmentioning

confidence: 99%

Nutritional regulation of leptin in humans

Coleman

Herrmann

1999

Diabetologia

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“…The proposed mechanism seems to affect the phospholipase C (PLC)/protein kinase C (PKC)-mediated pathway regulating insulin secretion. Modulation by leptin of several steps in this pathway were described: lowering of intracellular Ca 2+ concentration and activation of ATP-sensitive K + channels (166,169,173); a speci®c inhibition of PLC-mediated insulin secretion, which is enhanced in ob/ob mice (167,174); and reduction of PKC, a Ca 2+ -dependent mediator in the second phase of the PLC signal pathway (167,170). The insulinsuppressive effect of leptin could also partly be mediated by activation of phosphodiesterase 3B (171,175), leading to suppression of cAMP levels and inhibition of GLP-1-stimulated insulin secretion.…”

Section: Effect Of Leptin On Insulin Secretionmentioning

confidence: 99%

Human leptin: from an adipocyte hormone to an endocrine mediator

2000

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Leptin is a mainly adipocyte-secreted protein that was discovered 5 years ago. Most of the research following this discovery focused on the role of leptin in body weight regulation, aiming to illuminate the pathophysiology of human obesity. However, more and more data are emerging that leptin is not only important in the regulation of food intake and energy balance, but that it also has a function as a metabolic and neuroendocrine hormone. It is now clear that it is especially involved in glucose metabolism, as well as in normal sexual maturation and reproduction. Besides this, interactions with the hypothalamic±pituitary±adrenal, thyroid and GH axes and even with haematopoiesis and the immune system have also been described. It has been shown that leptin secretion by the adipocyte is partly regulated by other hormones, such as insulin, cortisol, and sex steroids, mainly testosterone. Also, other hormones like thyroid hormone and GH are possibly involved in leptin synthesis. Leptin itself exerts effects on different endocrine axes, mainly on the hypothalamic±pituitary±gonadal axis and on insulin metabolism, but also on the hypothalamic±pituitary±adrenal, thyroid and GH axes.Leptin may thus be considered a new endocrine mediator, besides its obvious role in body weight regulation.

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“…Indeed, leptin is known to directly reduce insulin secretion from pancreatic b cells. 23,24 Second, given that a high-fat diet has a lower content in carbohydrate, a same amount of food is expected to lead to a lower insulin response (i.e., to a lower plasma insulin) with a high-fat diet compared to that with the chow diet.…”

Section: Induction Of Dietary Obesity and Circadian Desynchronizationmentioning

confidence: 99%

Combined effects of high-fat feeding and circadian desynchronization

et al. 2005

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Objective: To assess whether circadian desynchronization leads to metabolic alterations capable of promoting dietary obesity and/or impairing glucose tolerance. Design: Rats fed either with chow pellets (i.e., low-fat diet with 4% mass of fat) or high-fat diet (34% mass of fat). Half of each diet group was exposed to a fixed light-dark cycle or to a 10-h weekly shift in the light-dark cycle from Thursday to Sunday (20 shifts). To enforce the shifted animals to be active at unusual times of the day, food was available only during the daily dark period for all groups. Results: Shifting the light-dark cycle on a weekly basis was efficient to induce circadian desynchronization, as evidenced by strong disturbances in the daily expression of locomotor activity. Shifted rats fed with a nocturnal low-fat diet had lower plasma insulin and similar blood glucose compared to rats fed with the same diet under a fixed light-dark cycle. Nocturnal high-fat feeding led to an abdominal fat overload associated with increased plasma leptin and basal glucose. These metabolic changes were not significantly modified by circadian desynchronization. Conclusion: Chronic desynchronization with low-fat diet impaired insulin regulation. Metabolic changes induced by the highfat diet were not aggravated by chronic desynchronization.

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Leptin: A Potent Inhibitor of Insulin Secretion

Cited by 93 publications

References 41 publications

Nutritional regulation of leptin in humans

Nutritional regulation of leptin in humans

Human leptin: from an adipocyte hormone to an endocrine mediator

Combined effects of high-fat feeding and circadian desynchronization

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