Obesity- and aging-induced excess of central transforming growth factor-β potentiates diabetic development via an RNA stress response.

ABSTRACT: The brain, in particular the hypothalamus, plays a role in regulating glucose homeostasis; however, it remains unclear whether this organ is causally and etiologically involved in the development of diabetes. Here, we found that hypothalamic transforming growth factor-β (TGF-β) production is excessive under conditions of not only obesity but also aging, which are two general etiological factors of type 2 diabetes. Pharmacological and genetic approaches revealed that central TGF-β excess caused hyperglycemia and glucose intolerance independent of a change in body weight. Further, using cell-specific genetic analyses in vivo, we found that astrocytes and proopiomelanocortin neurons are responsible for the production and prodiabetic effect of central TGF-β, respectively. Mechanistically, TGF-

SUBMITTER: Yan J 

PROVIDER: S-EPMC4167789 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature