Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion

Emilsson, V.; Liu, Y. L.; Cawthorne, Michael A.; Morton, N. M.; Davenport, M.

doi:10.2337/diabetes.46.2.313

Cited by 261 publications

(270 citation statements)

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“…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]. As would be expected, leptin blocked insulin secretion by islets from ob/ob mice but not by db/db mice which lack the leptin receptor [65]. These effects may be mediated by the ATP-sensitive potassium channel [66,67].…”

Section: Regulation Of Leptin By Insulinmentioning

confidence: 82%

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: 82%

Nutritional regulation of leptin in humans

Coleman

Herrmann

1999

Diabetologia

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“…O receptor Ob-Rb faz parte da família de receptores das citoquinas, ativando o sistema JAK/STAT de transdução do sinal após sua ligação com a leptina (24). A forma longa do receptor foi encontrada nos mais diversos órgãos incluindo pâncreas, rim, medula adrenal, placenta, ovários e tecido adiposo (25)(26)(27). Uma forte presença da expressão do gene do receptor Ob-Rb é vista nos diversos núcleos hipotalâmicos que regulam a ingestão alimentar e o controle do gasto energético (28).…”

Section: Receptor E Mecanismo De Açãounclassified

Leptina: o diálogo entre adipócitos e neurônios

Negrão¹,

Licinio

2000

Arq Bras Endocrinol Metab

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The discovery of leptin led to a renewed interest in the study of enegy homeostasis. It is now recognized that white adipose tissue is the major site of leptin synthesis. After it is secreted into the bloodstream leptin binds itself to specific receptors in the brain, providing the central nervous system with a satiety signal that reflects the amount of energy stored as fat. Acting through receptors that transduce a signal by the JAK/STAT pathway, leptin modifies the expression and activity of hypothalamic peptides that regulate appetite and energy expenditure. In addition, leptin signals nutritional status to other physiological systems and modulates the function of several target glands. More recently, recombinant leptin was successfully given to an obese patient with leptin deficiency due to a mutation in the ob gene. On the other hand, the effects of recombinant leptin in the only study with obese patients and increased levels of circulating leptin were less impressive.Here we review the complexity of leptin actions with a focus on its integrative role as a signal of nutritional status for the organism.

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“…At 100 nM leptin concentration the islets' insulin secretion response decreased to near 20% of the control group. At physiological leptin concentrations (1 nM) there was an apparent but nonsignificant reduction in insulin secretion (19). Supraphysiological leptin concentrations were necessary to elicit a significant reduction in insulin secretion from the islets.…”

Section: Leptin and The Endocrine Pancreasmentioning

confidence: 90%

“…It has been shown that a functional fulllength leptin receptor (Ob-Rb) is present in ob/ob mice islets (19), and recombinant leptin (1-100 nM) inhibits insulin secretion in a dose-dependent manner in islets isolated from these animals. However, the same effect was not detected in animals lacking the leptin receptor (fa/fa rats and db/db mice).…”

Section: Leptin and The Endocrine Pancreasmentioning

confidence: 99%

“…Analysis of the expression pattern of the two forms (long and short) of leptin receptors by Northern blot, in situ hybridization and quantitative PCR showed that the receptors are expressed in most tissues (brain, testes, ovary, kidney, spleen, intestines, brown and white adipose tissues, heart, lung, liver, skeletal muscle, and adrenals (14,18)), with the long form being prevalent in the hypothalamus (18), in addition to also being found in the medulla of the adrenal, the inner zone of the medulla of the kidney (16,18), pancreatic islets (19), and fat tissue (18).…”

Section: The Leptin Receptormentioning

confidence: 99%

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Pivotal role of leptin in insulin effects

Ceddia

William

Lima

et al. 1998

Braz J Med Biol Res

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The OB protein, also known as leptin, is secreted by adipose tissue, circulates in the blood, probably bound to a family of binding proteins, and acts on central neural networks regulating ingestive behavior and energy balance. The two forms of leptin receptors (long and short forms) have been identified in various peripheral tissues, a fact that makes them possible target sites for a direct action of leptin. It has been shown that the OB protein interferes with insulin secretion from pancreatic islets, reduces insulin-stimulated glucose transport in adipocytes, and increases glucose transport, glycogen synthesis and fatty acid oxidation in skeletal muscle. Under normoglycemic and normoinsulinemic conditions, leptin seems to shift the flux of metabolites from adipose tissue to skeletal muscle. This may function as a peripheral mechanism that helps control body weight and prevents obesity. Data that substantiate this hypothesis are presented in this review.

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Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion

Cited by 261 publications

References 0 publications

Nutritional regulation of leptin in humans

Nutritional regulation of leptin in humans

Leptina: o diálogo entre adipócitos e neurônios

Pivotal role of leptin in insulin effects

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