title: Orexin A regulates plasma insulin and leptin levels in a time-dependent manner following a glucose load in mice.
abstract: OBJECTIVE
  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
  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.
authors: Department of Physiology, Keimyung University School of Medicine, 1095 Dalgubeoldae-Ro, Dalseo-Gu, Daegu, 704-701, South Korea.
authors: Jae-Hyung
authors: JH
authors: Park
authors: Hae-Min
authors: HM
authors: Shim
authors: Ann-Yae
authors: AY
authors: Na
authors: Jae-Hoon
authors: JH
authors: Bae
authors: Seung-Soon
authors: SS
authors: Im
authors: Dae-Kyu
authors: DK
authors: Song
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D059305:Diet, High-Fat; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D064446:Orexin Receptors / Q000187:drug effects; D000068797:Orexins / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D020662:Guanine Nucleotide Exchange Factors; D007328:Insulin; D020738:Leptin; D064446:Orexin Receptors; D000068797:Orexins; C486707:Rapgef4 protein, mouse; D005934:Glucagon; D005947:Glucose; D002118:Calcium