Orexin A regulates plasma insulin and leptin levels in a time-dependent manner following a glucose load in mice
- Jae-Hyung Park; Hae-Min Shim; Ann-Yae; Jae-Hoon Bae; Seung-Soon Im; Dae-Kyu Song
- Dept. of Physiology (생리학)
- Issue Date
- Diabetologia, Vol.58(7) : 1542-1550, 2015
- 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 Ca2+ 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
Results OXA significantly potentiated glucose-stimulated insulin
secretion in vitro, which increased intracellular Ca2+ levels,
mainly through adenylate cyclase and ryanodine receptor activation.
This Ca2+-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.
- Epac2; Glucagon; Insulin secretion; Leptin; OrexinA; Rapgef4; Type 2 diabetes
- Appears in Collections:
- 1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
- Keimyung Author(s)
- 박재형; 배재훈; 임승순; 송대규
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