The role of leptin in glucose homeostasis

Denroche, Heather C.; Huynh, Frank K.; Kieffer, Timothy J.

doi:10.1111/j.2040-1124.2012.00203.x

Cited by 134 publications

(125 citation statements)

References 233 publications

(392 reference statements)

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…The centrally mediated action of leptin is that autonomic efferents increase direct leptin action on the pancreas and insulinsensitive tissues via activation of the hypothalamus. 38 From these reasons, in the leptin-deficient state such as in ob/ob mice, hyperglycemia is induced with combined overnutrition, obesity, and hyperinsulinemia.…”

Section: Discussionmentioning

confidence: 99%

Detrimental Effects of Leptin on Intracerebral Hemorrhage via the STAT3 Signal Pathway

Kim

Ryu

Choi

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Leptin, one of the most important adipokines, is not only an energy regulator but also a regulator of innate immunity. Inflammation plays a key role in the tissue damage after intracerebral hemorrhage (ICH), and we sought to investigate whether leptin has a detrimental effect on ICH. After the injection of a high replacement dose (0.04 mg/kg) and two pharmacologic doses (4 and 8 mg/kg) of leptin, brain water contents increased significantly compared with that of control mice (Po0.05), which was confirmed when comparing the results with leptin-deficient ob/ob and wild-type (WT) mice (78.8% ± 0.6% versus 79.7% ± 0.6%, Po0.05). The number of Ox6-positive microglia/macrophages was increased in the leptin-injected group and decreased in ob/ob compared with WT mice. Among the candidate signal transducers, an increase in signal transduction and activator of transcription 3 (STAT3) levels was found after leptin injection. When we administered NSC74859, a specific inhibitor of phosphorylated STAT3 (pSTAT3), the water content became normalized. Activity of pSTAT3 was found mainly in Ox6-positive microglia/macrophages, but not in either neurons or astrocytes. We demonstrate that leptin plays a critical role in the secondary brain injury around a hematoma and is a novel mediator of the inflammation. This detrimental effect of leptin on ICH is mediated by the STAT3 signaling pathway in inflammatory cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Detrimental Effects of Leptin on Intracerebral Hemorrhage via the STAT3 Signal Pathway

Kim

Ryu

Choi

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…However, there is now substantial evidence that leptin also plays a primary role in the regulation of glucose homeostasis. 1 The direct and central mechanisms that mediate the glucose-lowering effects of leptin in diabetes mellitus (DM) are still an area of active investigation. Leptin receptors are widely expressed in peripheral tissues, including the endocrine pancreas, liver, skeletal muscle, and adipose tissue.…”

Section: Introductionmentioning

confidence: 99%

“…Direct leptin action on skeletal muscle can either increase or decrease glucose uptake and insulin-stimulated glucose metabolism. 1,2 Centrally mediated actions of leptin on tissues conclude in activating leptin-responsive relays initiating in the hypothalamus that mediate leptin action on the endocrine pancreas and insulin-sensitive tissues through sympathetic and parasympathetic nervous systems. [1][2][3] Both leptin deficiency and leptin resistance profoundly affect glucose metabolism in rodents and humans.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 Centrally mediated actions of leptin on tissues conclude in activating leptin-responsive relays initiating in the hypothalamus that mediate leptin action on the endocrine pancreas and insulin-sensitive tissues through sympathetic and parasympathetic nervous systems. [1][2][3] Both leptin deficiency and leptin resistance profoundly affect glucose metabolism in rodents and humans. 3 One of the potentially effective therapeutic approaches to regenerating islet cells is fetal pancreatic stem cell transplant (FPSCT).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Untitled

2016

Exp Clin Transplant

View full text Add to dashboard Cite

Objectives: We aimed to determine leptin level in patients with type 2 diabetes mellitus after fetal pancreatic stem cell transplant. Materials and Methods: We examined 14 patients (aged 43-63 years old) with type 2 diabetes mellitus, which we subsequently divided into 2 groups and examined. Group 1 comprised 8 patients who received fetal pancreatic stem cell transplant (cells were 16-18 wk gestation) performed by intravenous infusion; group 2 comprised 6 patients in the control group who were on hypoglycemic tablet therapy or insulin therapy. The quantity of fetal stem cells infused was 5 to 6 × 10 6 . We analyzed leptin and C-peptide levels in patients both before and 3 months after the fetal pancreatic stem cell transplant procedure. Results: In patients with type 2 diabetes mellitus, fetal pancreatic stem cell transplant led to a significant increase in leptin levels, from 11.01 ng/mL to 16.29 ng/mL, after 3 months (P < .05). Conclusions: Leptin level increase significantly within 3 months after fetal pancreatic stem cell transplant in patients with type 2 diabetes mellitus.

show abstract

“…A number of studies show that leptin also plays a primary role in the regulation of glucose homeostasis [13]. For instance, leptin administration in rodents enhances insulin mediated suppression of hepatic glucose production [14,15] and suppress [16] hepatic gluconeogenesis.…”

mentioning

confidence: 99%

Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice

Cheng

Zhang

et al. 2015

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

X. (2015). Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice. Molecular and Cellular Endocrinology, Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice AbstractEpidemiological evidence suggests that the consumption of a diet high in n-6 polyunsaturated fatty acids (PUFA) is associated with the development of leptin resistance and obesity. We aim to examine the central effect of n-6 PUFA, arachidonic acid (ARA) on leptin sensitivity and leptin-regulated hepatic glucose and lipid metabolism. We found that intracerebroventricular injection of ARA (25 nmol/day) for 2.5 days reversed the effect of central leptin on hypothalamic JAK2, pSTAT3, pAkt, and pFOXO1 protein levels, which was concomitant with a pro-inflammatory response in the hypothalamus. ARA also attenuated the effect of central leptin on hepatic glucose and lipid metabolism by reversing the mRNA expression of the genes involved in gluconeogenesis (G6Pase, PEPCK), glucose transportation (GLUT2), lipogenesis (FAS, SCD1), and cholesterol synthesis (HMG-CoA reductase). These results indicate that an increased exposure to central n-6 PUFA induces central cellular leptin resistance with concomitant defective JAK2-STAT3 and PI3K-Akt signaling. Disciplines Medicine and Health Sciences 2 AbstractEpidemiological evidence suggests that the consumption of a diet high in n-6 polyunsaturated fatty acids

show abstract

The role of leptin in glucose homeostasis

Cited by 134 publications

References 233 publications

Detrimental Effects of Leptin on Intracerebral Hemorrhage via the STAT3 Signal Pathway

Detrimental Effects of Leptin on Intracerebral Hemorrhage via the STAT3 Signal Pathway

Untitled

Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice

Contact Info

Product

Resources

About