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Role of orexin in the regulation of glucose homeostasis
Author(s) -
Tsuneki H.,
Wada T.,
Sasaoka T.
Publication year - 2010
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2009.02008.x
Subject(s) - orexin , endocrinology , medicine , orexin a , energy homeostasis , leptin , insulin resistance , leptin receptor , glucose homeostasis , hypothalamus , biology , lateral hypothalamus , orexin receptor , receptor , homeostasis , neuropeptide , insulin , obesity
Orexin‐A (hypocretin‐1) and orexin‐B (hypocretin‐2) are hypothalamic neuropeptides that play key roles in the regulation of wakefulness, feeding, reward, autonomic functions and energy homeostasis. To control these functions indispensable for survival, orexin‐expressing neurones integrate peripheral metabolic signals, interact with many types of neurones in the brain and modulate their activities via the activation of orexin‐1 receptor or orexin‐2 receptor. In addition, a new functional role of orexin is emerging in the regulation of insulin and leptin sensitivities responsible for whole‐body glucose metabolism. Recent evidence indicates that orexin efficiently protects against the development of peripheral insulin resistance induced by ageing or high‐fat feeding in mice. In particular, the orexin receptor‐2 signalling appears to confer resistance to diet‐induced obesity and insulin insensitivity by improving leptin sensitivity. In fact, the expression of orexin gene is known to be down‐regulated by hyperglycaemia in the rodent model of diabetes, such as ob/ob and db/db mice. Moreover, the levels of orexin receptor‐2 mRNA have been shown to decline in the brain of mice along with ageing. These suggest that hyperglycaemia due to insulin insensitivity during ageing or by habitual consumption of a high‐fat diet leads to the reduction in orexin expression in the hypothalamus, thereby further exacerbating peripheral insulin resistance. Therefore, orexin receptor controlling hypothalamic insulin/leptin actions may be a new target for possible future treatment of hyperglycaemia in patients with type 2 diabetes.