Midgut-Derived Activin Regulates Glucagon-like Action in the Fat Body and Glycemic Control.
作者信息
Song Wei, Cheng Daojun, Hong Shangyu, Sappe Benoit, Hu Yanhui, Wei Neil, Zhu Changqi, O'Connor Michael B, Pissios Pavlos, Perrimon Norbert
机构信息
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China.
出版信息
Cell Metab. 2017 Feb 7;25(2):386-399. doi: 10.1016/j.cmet.2017.01.002.
While high-caloric diet impairs insulin response to cause hyperglycemia, whether and how counter-regulatory hormones are modulated by high-caloric diet is largely unknown. We find that enhanced response of Drosophila adipokinetic hormone (AKH, the glucagon homolog) in the fat body is essential for hyperglycemia associated with a chronic high-sugar diet. We show that the activin type I receptor Baboon (Babo) autonomously increases AKH signaling without affecting insulin signaling in the fat body via, at least, increase of Akh receptor (AkhR) expression. Further, we demonstrate that Activin-β (Actβ), an activin ligand predominantly produced in the enteroendocrine cells (EEs) of the midgut, is upregulated by chronic high-sugar diet and signals through Babo to promote AKH action in the fat body, leading to hyperglycemia. Importantly, activin signaling in mouse primary hepatocytes also increases glucagon response and glucagon-induced glucose production, indicating a conserved role for activin in enhancing AKH/glucagon signaling and glycemic control.