Midgut-Derived Activin Regulates Glucagon-like Action in the Fat Body and Glycemic Control

Wei Song, Daojun Cheng, Shangyu Hong, Benoit Sappe, Yanhui Hu, Neil Wei, Changqi Zhu, Michael B. O'Connor, Pavlos Pissios, Norbert Perrimon

Research output: Contribution to journalArticle

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)386-399
Number of pages14
JournalCell Metabolism
Volume25
Issue number2
DOIs
StatePublished - Feb 7 2017

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    Song, W., Cheng, D., Hong, S., Sappe, B., Hu, Y., Wei, N., Zhu, C., O'Connor, M. B., Pissios, P., & Perrimon, N. (2017). Midgut-Derived Activin Regulates Glucagon-like Action in the Fat Body and Glycemic Control. Cell Metabolism, 25(2), 386-399. https://doi.org/10.1016/j.cmet.2017.01.002