Modulation of insulin secretion by leptin

Ceddia, Rolando B.; William, William Nassib; Carpinelli, Ângelo Rafael; Curi, Rui

doi:10.1016/s0306-3623(98)00185-2

Cited by 24 publications

(16 citation statements)

References 15 publications

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“…While a number of in vitro studies have yielded controversial results for the effects of leptin on insulin secretion (Leclercq-Meyer et al 1996, Ahren & Harvel 1999, Ceddia et al 1999, Lupi et al 1999, there is now convincing evidence in vitro and in vivo that leptin suppresses insulin secretion and gene expression in pancreatic islets , Poitout et al 1998, Seufert et al 1999a. These studies show that leptin suppresses insulin production from pancreatic -cells and the presence of OB-R on pancreatic -cells suggests a functional relationship between circulating leptin and insulin secretion.…”

Section: Discussionmentioning

confidence: 97%

“…When, on the other hand, adipose stores decrease, falling plasma leptin concentrations permit increased insulin production, thereby resulting in the deposition of additional fat. The negative feedback of leptin on insulin gene transcription and insulin secretion in pancreatic islets is well established (Ceddia et al 1999, Lupi et al 1999, Seufert et al 1999a. However, more recent evidence suggests that defective leptin reception by pancreatic -cells may be a key mechanism for obesity-associated hyperinsulinism and may contribute to the pathogenesis of adipogenic diabetes (Seufert et al 1999b).…”

Section: Introductionmentioning

confidence: 99%

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Dysregulation of the adipoinsular axis -- a mechanism for the pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal programming

Vickers¹,

Reddy²,

Ikenasio³

et al. 2001

Journal of Endocrinology

142

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Obesity and its related disorders are the most prevalent health problems in the Western world. Using the paradigm of fetal programming we developed a rodent model which displays the phenotype of obesity and metabolic disorders commonly observed in human populations. We apply maternal undernutrition throughout gestation, generating a nutrient-deprived intrauterine environment to induce fetal programming. Maternal undernutrition results in fetal growth retardation and in significantly decreased body weight at birth. Programmed offspring develop hyperphagia, obesity, hypertension, hyperleptinemia and hyperinsulinism during adult life and postnatal hypercaloric nutrition amplifies the metabolic abnormalities induced by fetal programming. The adipoinsular axis has been proposed as a primary candidate for linking the status of body fat mass to the function of the pancreatic -cells. We therefore investigated the relationship between circulating plasma concentrations of leptin and insulin and immunoreactivity in the endocrine pancreas for leptin and leptin receptor (OB-R) in genetically normal rats that were programmed to become obese during adult life. Virgin Wistar rats were time mated and randomly assigned to receive food either available ad libitum (AD group) or at 30% of the ad libitum available intake (UN group). Offspring from UN mothers were significantly smaller at birth than AD offspring (AD 6·13 0·04 g, UN 4·02 0·03 g, P<0·001). At weaning, offspring were assigned to one of two diets (a standard control diet or a hypercaloric diet consisting of 30% fat) for the remainder of the study. At the time of death (125 days of age), UN offspring had elevated (P<0·005) fasting plasma insulin (AD control 1·417 0·15 ng/ml, UN control 2·493 0·33 ng/ml, AD hypercaloric 1·70 0·17 ng/ml, UN hypercaloric 2·608 0·41 ng/ml) and leptin (AD control 8·8 1·6 ng/ml, UN control 14·32 1·9 ng/ml, AD hypercaloric 15·11 1·8 ng/ml, UN hypercaloric 30·18 5·3 ng/ml) concentrations, which were further increased (P<0·05) by postnatal hypercaloric nutrition. The elevated plasma insulin and leptin concentrations were paralleled by increased immunolabeling for leptin in the peripheral cells of the pancreatic islets. Dual immunofluorescence histochemistry for somatostatin and leptin revealed that leptin was co-localized in the pancreatic -cells. OB-R immunoreactivity was evenly distributed throughout the pancreatic islets and was not changed by programming nor hypercaloric nutrition. Our data suggest that reduced substrate supply during fetal development can trigger permanent dysregulation of the adipoinsular feedback system leading to hyperleptinemia, hyperinsulinism and compensatory leptin production by pancreatic -cells in a further attempt to reduce insulin hypersecretion in the progression to adipogenic diabetes.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Dysregulation of the adipoinsular axis -- a mechanism for the pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal programming

Vickers¹,

Reddy²,

Ikenasio³

et al. 2001

Journal of Endocrinology

142

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“…It has been demonstrated that the transport of leptin across the blood-brain barrier is saturated at plasma leptin levels between 4 and 15 ng/ml, nevertheless, exogenously elevated plasma leptin levels (above 15 ng/ml) elicit reduction in fat mass and improvements of glucose uptake and insulin sensitivity in rats, 55,70 suggesting that direct peripheral effects of leptin may be responsible for these metabolic alterations caused by leptin treatment. It has been repeatedly demonstrated that leptin exerts its effects by also acting directly in peripheral tissues such as skeletal muscle, 28,29,33,34,37,38 fat tissue, 66,68,70,71 pancreas, [89][90][91] and liver, 92 which play important roles in the regulation of glucose and fatty acids metabolism and whole-body energy homeostasis in mammals. Additionally, it has been reported that isolated soleus muscles from highfat diet-induced obese (HFDIO) rats are not sensitive to the leptin-induced increase in fatty acid oxidation, 38 suggesting that the development of leptin resistance in skeletal muscle may contribute to the intramuscular accumulation of lipids.…”

Section: Physiological and Molecular Mechanisms Of Leptin Resistancementioning

confidence: 99%

Direct metabolic regulation in skeletal muscle and fat tissue by leptin: implications for glucose and fatty acids homeostasis

2005

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In recent years, the adipose tissue has emerged as an important endocrine organ. It is now recognized that besides storing energy the adipocytes also secrete several bioactive peptides, collectively called adipocytokines. Among these adipocytokines, leptin, the product of the ob gene, has been extensively investigated over the last decade. Skeletal muscle and adipose tissue, two major tissues involved in the regulation of glucose and fatty acids metabolism, have been consistently demonstrated to be directly affected by leptin. By binding to its receptors located in skeletal muscle and fat cells, leptin promotes energy dissipation and prevents fatty acid accumulation and 'lipotoxicity' in these tissues. On the other hand, under conditions of peripheral leptin resistance, such as observed in obese humans, the activation of pathways involved in fatty acid oxidation may be impaired. This leads to intracellular accumulation of lipid intermediates and causes insulin resistance. This review examines the metabolic pathways that are directly activated by leptin and how it regulates glucose and fatty acids metabolism in skeletal muscle and fat tissue. Furthermore, the impact of peripheral leptin resistance in these tissues leading to dysfunctional metabolic adaptations is also discussed.

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“…Many in vitro studies performed with rat and human pancreatic islets, and insulin secreting cell lines provide the evidence for the existence of adipo-insular axis. Leptin shows inhibitory effect, as a negative feedback signal from adipose tissue to the endocrine pancreas, on glucose stimulated insulin secretion (Ookuma et al 1998, Ceddia et al 1999, Seufert et al 1999. Some studies, however, have reported that depending upon the dose of leptin, leptin exposure time, and glucose concentration, insulin secretion from pancreatic b cells is either increased (Shimizu et al 1997, Tanizawa et al 1997 or may even remain unaffected (Leclercq-Meyer & Malaisse 1998).…”

Section: Role Of Leptin In Bat Ovarymentioning

confidence: 99%

Adiposity associated rise in leptin impairs ovarian activity during winter dormancy in Vespertilionid bat, Scotophilus heathi

Srivastava¹,

Krishna²

2007

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The aim of the study was to evaluate the seasonal variation in serum leptin levels in a natural population of the female bat, Scotophilus heathi and their relationship to the changes in the body mass, serum insulin level, and ovarian activity. Circulating leptin level varied significantly over the season and correlated positively with the changes in body mass, and circulating insulin and androstenedione (A4) levels. Circulating leptin concentrations showed two peaks; one coincides with the maximum fat accumulation prior to winter dormancy, whereas the second shorter peak coincides with late pregnancy. The in vivo study in S. heathi showed that the increased circulating leptin level during winter dormancy coincides with the decreased expression of ovarian steroidogenic acute regulatory (StAR) protein, and low circulating estradiol (E 2 ) level. At the same time, increased circulating leptin level coincides with increased expression of ovarian insulin receptor and high circulating A4 level. The low circulating leptin level during preovulatory period coincides with the increase in StAR protein but decrease in insulin receptor protein. The in vitro study confirmed the in vivo observations of inhibitory effect of leptin on LH induced StAR expression and E 2 production, whereas the stimulatory effect of leptin (high dose) on LH induced expression of insulin receptor protein and A4 production. However, pharmacological dose of leptin produced inhibitory effect on the expression of insulin receptor protein.The results of the present study thus suggest that high circulating leptin level during winter dormancy promotes adiposity and impairs ovarian activity by suppressing StAR-mediated E 2 production as well as by enhancing insulin receptor-mediated A4 synthesis thereby contributing anovulatory condition of delayed ovulation in S. heathi.

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Modulation of insulin secretion by leptin

Cited by 24 publications

References 15 publications

Dysregulation of the adipoinsular axis -- a mechanism for the pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal programming

Dysregulation of the adipoinsular axis -- a mechanism for the pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal programming

Direct metabolic regulation in skeletal muscle and fat tissue by leptin: implications for glucose and fatty acids homeostasis

Adiposity associated rise in leptin impairs ovarian activity during winter dormancy in Vespertilionid bat, Scotophilus heathi

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