Leptin Inhibits Insulin Secretion and Reduces Insulin mRNA Levels in Rat Isolated Pancreatic Islets

Pallett, Anna L.; Morton, Nicholas M.; Cawthorne, Michael A.; Emilsson, Valur

doi:10.1006/bbrc.1997.7274

Cited by 119 publications

(86 citation statements)

References 21 publications

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“…5-100 nM, leptin reduces insulin release in HIT-T15, b-TC6, and INS-1 cells (Kulkarni et al 1997, Zhao et al 1998, Tsiotra et al 2001, Kuehnen et al 2011). Similar observations have been obtained in isolated pancreatic islets of ob/ob and normal mice, rats as well as in perfused pancreas at concentrations ranging from 1 pM to 100 nM (Kieffer et al 1997, Kulkarni et al 1997, Pallett et al 1997, Zhao et al 1998). These effects have been reported for a variety of glucose concentrations from low to high levels.…”

Section: Regulation Of Insulin Secretion By Leptinsupporting

confidence: 71%

“…, Seufert et al 1999a, Tsiotra et al 2001. Analysis of proinsulin mRNA levels revealed a decrease in isolated rat islets after incubation with 1-10 nM leptin (Kulkarni et al 1997, Pallett et al 1997. This effect has also been observed in ob/ob mice treated in vivo with leptin and in in vitro experiments with isolated islets from these animals (Seufert et al 1999a).…”

Section: Regulation Of Insulin Secretion By Leptinmentioning

confidence: 95%

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Role of leptin in the pancreatic β-cell: effects and signaling pathways

Marroquí¹,

González²,

Ñeco³

et al. 2012

Journal of Molecular Endocrinology

134

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Leptin plays an important role in the control of food intake, energy expenditure, metabolism, and body weight. This hormone also has a key function in the regulation of glucose homeostasis. Although leptin acts through central and peripheral mechanisms to modulate glucose metabolism, the pancreatic b-cell of the endocrine pancreas is a critical target of leptin actions. Leptin receptors are present in the b-cell, and their activation directly inhibits insulin secretion from these endocrine cells. The effects of leptin on insulin occur also in the long term, since this hormone inhibits insulin gene expression as well. Additionally, b-cell mass can be affected by leptin through changes in proliferation, apoptosis, or cell size. All these different functions in the b-cell are triggered by leptin as a result of the large diversity of signaling pathways that this hormone is able to activate in the endocrine pancreas. Therefore, leptin can participate in glucose homeostasis owing to different levels of modulation of the pancreatic b-cell population. Furthermore, it has been proposed that alterations in this level of regulation could contribute to the impairment of b-cell function in obesity states. In the present review, we will discuss all these issues with special emphasis on the effects and pathways of leptin signaling in the pancreatic b-cell.

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Section: Regulation Of Insulin Secretion By Leptinsupporting

confidence: 71%

Section: Regulation Of Insulin Secretion By Leptinmentioning

confidence: 95%

Role of leptin in the pancreatic β-cell: effects and signaling pathways

Marroquí¹,

González²,

Ñeco³

et al. 2012

Journal of Molecular Endocrinology

134

View full text Add to dashboard Cite

show abstract

“…1,2,8,21 Since leptin receptors are present in the pancreatic islets of rodents, 23 it has been speculated that leptin may directly regulate insulin secretion from the b-cell. In accordance with this, leptin treatment in vitro has been shown to inhibit GSIS in islets from obaob and lean mice, 9,10 normal rats 24,25 and humans. 26,27 In other studies, leptin was without any effect on GSIS.…”

Section: Discussionmentioning

confidence: 65%

Long-term leptin treatment of ob/ob mice improves glucose-induced insulin secretion

et al. 2001

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OBJECTIVE: Previous studies have demonstrated that leptin inhibits glucose-stimulated insulin secretion from isolated islets, although a lack of leptin effect on insulin secretion has also been reported. The effect of long term in vivo leptin treatment of insulin secretion has, however, not been established. Therefore, in the present study, we have evaluated the effect of long term in vivo treatment of leptin on glucose-induced insulin secretion in obaob mice. METHODS: After 7 days' treatment of leptin (100 mg daily s.c.), insulin release was measured in isolated islets by batch incubation followed by radioimmunoassay. Glucose utilization and oxidation were measured by measuring the formation of 3 H 2 O and 14 CO 2 from [5-3 H] and [U-14 C] glucose, respectively. Glucose-6-phosphatase activity was measured by measuring the conversion of 14 C-glucose-6-P to 14 C-glucose. In addition, immunohistochemistry of pancreatic specimens was undertaken for study of expression of insulin, GLUT-2 and hormone-sensitive lipase (HSL). RESULTS: Leptin treatment signi®cantly improved insulin secretion both at 5.5 mM (by 15%; P`0.05) and 16.7 mM (by 85%; P`0.001) glucose, compared to vehicle-treated controls. Furthermore, whereas leptin treatment did not affect islet insulin or DNA contents, a signi®cant decrease in islet triglyceride content and glucose-6-phosphatase activity was observed. Moreover, the immunocytochemical data revealed an increased immunostaining for insulin, GLUT-2 and hormone-sensitive lipase (HSL) in islets from leptin-treated obaob mice. CONCLUSION:The results suggest that long-term leptin treatment of obaob mice improves glucose-stimulated insulin secretion in parallel with reduced glucose-6-phosphatase activity, increased HSL and decreased triglyceride levels in islets. These perturbations may explain the improvement of glucose-stimulated insulin secretion induced by leptin.

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“…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. Recently, a direct effect of leptin on insulin gene transcription in pancreatic b-cells was shown, with a reduction of preproinsulin mRNA by 50% (168,176). Leptin probably acts at different intracellular levels, from transcription to membrane permeability, to inhibit insulin synthesis as well as 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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Leptin Inhibits Insulin Secretion and Reduces Insulin mRNA Levels in Rat Isolated Pancreatic Islets

Cited by 119 publications

References 21 publications

Role of leptin in the pancreatic β-cell: effects and signaling pathways

Role of leptin in the pancreatic β-cell: effects and signaling pathways

Long-term leptin treatment of ob/ob mice improves glucose-induced insulin secretion

Human leptin: from an adipocyte hormone to an endocrine mediator

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