Effects of orexin A on GLUT4 expression and lipid content via MAPK signaling in 3T3-L1 adipocytes

Shen, Yang; Yang, Zhao; Zheng, Delu; Chang, Xin; Ju, Shujing; Guo, Lei

doi:10.1016/j.jsbmb.2013.07.005

Cited by 31 publications

(32 citation statements)

References 40 publications

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“…A reduction in plasma OXA levels has been identified in rat [13] and mouse [32] models of obesity and type 2 diabetes and in obese humans with type 2 diabetes [33]. Interestingly, we observed that exogenous OXA markedly improved glucose tolerance in HID mice via potentiation of insulin and leptin secretion.…”

Section: Discussionsupporting

confidence: 50%

“…OXRs have been demonstrated not only in central neurons but also in some peripheral endocrine cells. Recent studies have demonstrated that OXR1 is expressed in the pancreatic alpha and beta cells of pigs, rats and mice [9][10][11] and in human and rat adipocytes [12,13]. Therefore, it is likely that orexins contribute to important endocrine functions.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

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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“…Recently, we and others showed that orexins regulate glucose and lipid metabolism by interacting with white adipose tissue. [9][10][11] In human adipocytes, OXA stimulates peroxisome proliferator-activated receptor gamma (PPAR) expression and suppresses lipolysis. 9 Studies on rodent adipocytes confirmed these observations and revealed the ability of OXA to enhance glucose uptake, triacylglycerol accumulation, as well as adiponectin expression and secretion.…”

Section: Introductionmentioning

confidence: 99%

“…9 Studies on rodent adipocytes confirmed these observations and revealed the ability of OXA to enhance glucose uptake, triacylglycerol accumulation, as well as adiponectin expression and secretion. 10,11 In contrast to mature adipocytes, knowledge is scarce regarding the role of orexins in preadipocytes. It was shown that OXA stimulates proliferation and inhibits apoptosis in mouse 3T3-L1 and rat primary preadipocytes, whereas it fails to modulate adipogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, contrary to our data, a recently published work reported that OXA stimulates Ppar mRNA expression in 3T3-L1 preadipocytes. 11 Shen et al studied the effects of OXA on Ppar expression alone. In our study, however, the effects of OXA on Ppar expression were assessed in the presence of 3-isobutyl-1-methylxanthin, which is a potent stimulus of PPARg expression in preadipocytes.…”

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confidence: 99%

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Original Research: Orexins A and B stimulate proliferation and differentiation of porcine preadipocytes

Wojciechowicz

Skrzypski

Szczepankiewicz

et al. 2016

Exp Biol Med (Maywood)

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Orexin A (OXA) and B (OXB) are neuropeptides which regulate appetite, energy expenditure, and arousal via G-protein coupled receptors termed as OXR1 and OXR2. The aim of this study was to characterize the effects of OXA and OXB on proliferation and differentiation of porcine preadipocytes. Porcine preadipocytes express both OXRs. OXA and OXB enhance porcine preadipocyte proliferation by 54.8% or 63.2 %, respectively. OXA and OXB potentiate differentiation of porcine preadipocytes, as judged by the increased lipid accumulation and expression of proadipogenic genes. Cellular lipid content after exposure of preadipocytes for six days to 100 nM OXA or OXB increased by 82.2% or 59.2%, respectively. OXA and OXB suppressed glycerol release by 23.9% or 24.9% in preadipocytes differentiated for six days. OXA (100 nM) increased peroxisome proliferator-activated receptor gamma (PPAR) expression in cells differentiated for 24 h by 100.5%. PPAR expression was also stimulated in preadipocytes differentiated in the presence of 10 nM (58.3%) or 100 nM OXA (50.6%) for three days. OXB potentiated PPAR mRNA expression at 1 nM (59%), 10 nM (53.2%), and 100 nM (73.9%) in cells differentiated for three days. OXA increased CCAAT/enhancer binding protein alpha expression in preadipocytes differentiated for six days by 65%. OXB stimulated CCAAT/enhancer binding protein beta expression in preadipocytes differentiated for three days at 10 nM (149.5%) as well as 100 nM (207.2%). Lipoprotein lipase mRNA expression increased in cells treated with 10 nM OXA by 152.6% and 100 nM OXA by 162%. Lipoprotein lipase expression increased by 134% at 100 nM OXB. Furthermore, OXA (100 nM) and OXB (100 nM) increased leptin mRNA expression in preadipocytes differentiated for three days by 49.9% or 71.3%, respectively. These data indicate that orexin receptors may be relevant in the context of white adipose tissue formation.

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Hypocretin/orexin modulates body weight and the metabolism of glucose and insulin

Adeghate

Lotfy

D’Souza

et al. 2020

Diabetes Metabolism Res

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Summary The hypocretin/orexin (Hcrt/orexin) unit affects the functions of the nervous, cardiovascular, gastrointestinal, and reproductive systems. Hcrt/orexin ligands and receptors have been localized to different parts of the central and peripheral nervous systems, cerebrospinal fluid and blood, exocrine (pancreas, salivary, lacrimal) as well as endocrine (pancreatic islets, pituitary, adrenal) glands. Several factors including stress, glucagon‐like peptide‐1 agonists, glutamate, nicotine, glucose, and hypoglycaemia stimulate the expression of Hcrt/orexin system, but it is inhibited by ageing, bone morphogenetic protein, hypoxia/hypercapnia, melanocortin receptor accessory protein 2, and glucagon. Literature reports show that Hcrt/orexin can significantly increase insulin secretion from normal and diabetic rat pancreata. Hcrt/orexin decreases blood glucose concentration and reduces insulin resistance partly via increased tissue expression of glucose transporter type 4. It reduces obesity by increasing browning of fat cells and energy expenditure. Taken together, Hcrt/orexin modulates obesity and the metabolism of glucose and insulin. The Hcrt/orexin system may thus be a target in the development of new therapies for the treatment of diabetes mellitus.

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Effects of orexin A on GLUT4 expression and lipid content via MAPK signaling in 3T3-L1 adipocytes

Cited by 31 publications

References 40 publications

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

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

Original Research: Orexins A and B stimulate proliferation and differentiation of porcine preadipocytes

Hypocretin/orexin modulates body weight and the metabolism of glucose and insulin

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