Leptin Receptors Expressed on Pancreatic β-Cells

Tj, Kieffer; Rs, Heller; Jf, Habener

doi:10.1006/bbrc.1996.1059

Cited by 320 publications

(215 citation statements)

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“…Previous studies have shown leptin to decrease basal insulin secretion from the pancreatic islets 34 and down-regulates insulin gene transcription. 35 Leptin receptors have been demonstrated on the β-pancreatic cell, 36 and in animal studies acute physiologic increases in leptin significantly inhibited glucose stimulated insulin secretion in a dose-dependent manner. 37 Plasma levels of leptin, adequate to significantly suppress insulin, are found in mild obesity 38 and patients with IGT.…”

Section: Neuropeptides and Impaired Glucose Tolerancementioning

confidence: 99%

Lack of Association Between Impaired Glucose Tolerance and Appetite Regulating Hormones in Patients with Obstructive Sleep Apnea

Patterson¹,

Twigg²,

Vazir³

et al. 2011

Journal of Clinical Sleep Medicine

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Study Objectives: Understanding the etiologic mechanisms underlying impaired glucose tolerance in obstructive sleep apnea (OSA) would assist development of therapies against this comorbidity. We hypothesized that in patients with OSA impaired glucose tolerance (IGT) would be associated with elevated levels of hormones associated with appetite regulation (leptin, ghrelin, neuropeptide Y [NPY] and peptide tyrosine-tyrosine [PYY]). Method: We studied 68 OSA patients (mean AHI 22 events/h) and 37 age and weight matched healthy controls recruited by advertisement. All participants received a standardized evening meal, attended polysomnography and an oral glucose tolerance test (OGTT) on waking. Hormones were measured in blood taken before sleep (22:30) and at the start of the OGTT. Results: Impaired glucose tolerance was present in 54% of patients and 32% of controls (p = 0.05). The only differences between groups was that leptin was signifi cantly higher at 22:30 in OSA patients compared to controls (9.6 ng/L vs 7.9 ng/L, p = 0.05). OSA patients had marginally elevated plasma NPY levels at 22:30 (56.6 [52, 67] S C I E N T I F I C I N v E S T I G A T I O N SU ntreated obstructive sleep apnea (OSA) is associated with insulin resistance, 1,2 and some studies suggest that treatment with CPAP improves glucose control, 3,4 although this was not found in a randomized controlled trial of diabetics with sleep apnea. 5 The observation that established type 2 diabetics cannot improve glucose control when their OSA is treated with CPAP, emphasizes the importance of understanding the pathophysiology of insulin resistance associated with OSA.One mechanism linking OSA with impaired glucose tolerance could be sympathetic nerve activity which is a recognized phenomenon in OSA 6 ; indeed it has previously been hypothesized that this process is responsible for the elevated leptin levels seen in newly diagnosed OSA patients. 7 Consistent with this sibutramine, a serotonin and noradrenaline reuptake inhibitor, was able to improve insulin resistance in OSA independent of visceral fat. 8 Moreover two studies raise the hypothesis that hormones involved in appetite regulation could contribute to impaired glucose tolerance. Broglio et al. 9 demonstrated that ghrelin administered to healthy subjects simultaneously with glucose, resulted in a transient decrease of insulin concentration that was coupled with signifi cant increase in glucose levels. In addition it has been reported that IR is associated with increased plasma leptin concentration independent of the body fat. 10 Consistent with this hypothesis, previous studies have reported that OSA is independently associated with neuroendocrine dysregulation; in fact OSA has been reported to be bRIEF SUMMARY Current knowledge/Study Rationale: Impaired glucose tolerance is a common and important co-morbidity of obstructive sleep apnea yet its pathogenesis, beyond the shared etiology of obesity is unknown. Here we tested the hypothesis that OSA might induce increases of appetite regulating h...

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Section: Neuropeptides and Impaired Glucose Tolerancementioning

confidence: 99%

Lack of Association Between Impaired Glucose Tolerance and Appetite Regulating Hormones in Patients with Obstructive Sleep Apnea

Patterson¹,

Twigg²,

Vazir³

et al. 2011

Journal of Clinical Sleep Medicine

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“…The existence of a correlation between serum resistin levels and insulin, insulin resistance and blood glucose levels supports this idea [25] . The role of leptin in modulating the immune response and inflammation has become increasingly evident and has been reviewed recently [26,27] . Complex interactions among the nervous, endocrine and immune systems affect the leptin loop and the potential role of these mediators in cancer-related cachexiaanorexia syndrome [8,11,12] .…”

Section: Resistin Ghrelin Leptin Adiponectin Igf-ⅰmentioning

confidence: 99%

Adipokines and ghrelin in gastric cancer cachexia

Kerem

Ferahköşe²,

Yılmaz³

et al. 2008

WJG

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AIM:To investigate the roles of the adipocytokines, ghrelin and leptin in gastric cancer cachexia. METHODS: Resistin, ghrelin, leptin, adiponectin, insulin and insulin-like growth factor (IGF-Ⅰ), were measured in 30 healthy subjects, and 60 gastric cancer patients of which 30 suffered from cancerinduced cachexia and 30 served as a control group. The relationships between hormones, body mass index (BMI) loss ratio, age, gender, and Glasgow Prognostic Score (GPS) were investigated. RESULTS: Cachexia patients had higher tumor stage and GPS when compared with non-cachexia patients (P < 0.05). Ghrelin, resistin, leptin, adiponectin and IGF-Ⅰ, showed a significant correlation with BMI loss ratio and GPS (P < 0.05). A strong correlation was seen between GPS and BMI loss (R = -0.570, P < 0.0001). Multivariate analysis indicated that BMI loss was significantly independent as a predictor of ghrelin, resistin, leptin and IGF-Ⅰ (P < 0.05). Existence of an important significant relationship between resistin and insulin resistance was also noted. CONCLUSION: These results showed that serum ghrelin, leptin, adiponectin, and IGF-Ⅰ play important roles in cachexia-related gastric cancers. No relationship was found between resistin and cancer cachexia. Also, because of the correlation between these parameters and GPS, these parameters might be used as a predictor factor.

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“…Moreover, leptin potently inhibits insulin secretion [21][22][23] whereas OXA exerts the opposite effect [11]. These findings suggest that leptin and orexins are strongly correlated with each other and that they have counteracting roles in the regulation of appetite and plasma insulin levels.…”

Section: Introductionmentioning

confidence: 86%

Orexin A regulates plasma insulin and leptin levels in a time-dependent manner following a glucose load in mice

Park

Shim

et al. 2015

Diabetologia

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Aims/hypothesis Orexin A (OXA) is a neuropeptide implicated in the regulation of arousal status and energy metabolism. Orexin receptors are expressed not only in the central nervous system but also in the pancreas and adipose tissue. However, little is known about the physiological function of orexins. This study investigated the role of exogenous OXA in blood glucose control after glucose load in mice. In addition, the effect of OXA on insulin secretion was also identified in mouse pancreatic beta cells. Methods Insulin secretion and intracellular Ca 2+ levels were measured in perifused mouse islets. To investigate the effects of exogenous OXA on blood glucose levels in vivo, intraperitoneal glucose tolerance tests were performed after a subcutaneous injection of OXA in normal and high-fat diet-induced diabetic mice. Results OXA significantly potentiated glucose-stimulated insulin secretion in vitro, which increased intracellular Ca 2+ levels, mainly through adenylate cyclase and ryanodine receptor activation. This Ca 2+ -dependent insulinotropic effect of OXA was blocked in Epac2 (Rapgef4)-deficient beta cells. After a glucose load in mice, exogenous OXA decreased blood glucose levels, compared with the control, by enhancing plasma insulin and decreasing plasma glucagon levels. Additionally, OXA caused a delayed increase in plasma leptin levels, resulting in lower plasma insulin levels when blood glucose levels fell to baseline. Conclusions/interpretation These results suggest that OXA might be a critical regulator of insulin, glucagon and leptin secretion in response to glucose. Thus, exogenous OXA might have therapeutic potential in improving blood glucose control in patients with type 2 diabetes.

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Leptin Receptors Expressed on Pancreatic β-Cells

Cited by 320 publications

References 0 publications

Lack of Association Between Impaired Glucose Tolerance and Appetite Regulating Hormones in Patients with Obstructive Sleep Apnea

Lack of Association Between Impaired Glucose Tolerance and Appetite Regulating Hormones in Patients with Obstructive Sleep Apnea

Adipokines and ghrelin in gastric cancer cachexia

Orexin A regulates plasma insulin and leptin levels in a time-dependent manner following a glucose load in mice

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