論文 - 詳細
RRC ID | 50316 |
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著者 | Song W, Cheng D, Hong S, Sappe B, Hu Y, Wei N, Zhu C, O'Connor MB, Pissios P, Perrimon N. |
タイトル | Midgut-Derived Activin Regulates Glucagon-like Action in the Fat Body and Glycemic Control. |
ジャーナル | Cell Metab |
Abstract |
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. |
巻・号 | 25(2) |
ページ | 386-399 |
公開日 | 2017-2-7 |
DOI | 10.1016/j.cmet.2017.01.002 |
PII | S1550-4131(17)30037-2 |
PMID | 28178568 |
PMC | PMC5373560 |
MeSH | Activin Receptors / metabolism Activins / metabolism* Animals Carbohydrate Metabolism Carrier Proteins / metabolism Dietary Carbohydrates / adverse effects Disease Models, Animal Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila melanogaster / metabolism* Enteroendocrine Cells / metabolism Fat Body / metabolism* Gastrointestinal Tract / metabolism* Glucagon / metabolism* Hepatocytes / metabolism Hyperglycemia / metabolism* Hyperglycemia / pathology Insect Hormones / metabolism Larva / metabolism Mice Oligopeptides / metabolism Pyrrolidonecarboxylic Acid / analogs & derivatives Pyrrolidonecarboxylic Acid / metabolism RNA Interference RNA, Messenger / genetics RNA, Messenger / metabolism Receptors, Glucagon / genetics Receptors, Glucagon / metabolism Signal Transduction |
IF | 21.567 |
引用数 | 41 |
リソース情報 | |
ショウジョウバエ | 11062R-1 11062R-2 |