SMOC1 is a glucose-responsive hepatokine and therapeutic target for glycemic control

MK Montgomery; J Bayliss; C Devereux; A Bezawork-Geleta; D Roberts; C Huang; RB Schittenhelm; A Ryan; SL Townley; LA Selth; TJ Biden; GR Steinberg; D Samocha-Bonet; RCR Meex; MJ Watt

Journal article

SMOC1 is a glucose-responsive hepatokine and therapeutic target for glycemic control

MK Montgomery, J Bayliss, C Devereux, A Bezawork-Geleta, D Roberts, C Huang, RB Schittenhelm, A Ryan, SL Townley, LA Selth, TJ Biden, GR Steinberg, D Samocha-Bonet, RCR Meex, MJ Watt

Science Translational Medicine | Published : 2020

DOI: 10.1126/SCITRANSLMED.AAZ8048

Abstract

Intertissue communication is a fundamental feature of metabolic regulation, and the liver is central to this process. We have identified sparc-related modular calcium-binding protein 1 (SMOC1) as a glucose-responsive hepatokine and regulator of glucose homeostasis. Acute intraperitoneal administration of SMOC1 improved glycemic control and insulin sensitivity in mice without changes in insulin secretion. SMOC1 exerted its favorable glycemic effects by inhibiting adenosine 3′,5′-cyclic monophosphate (cAMP)–cAMP-dependent protein kinase (PKA)–cAMP response element–binding protein (CREB) signaling in the liver, leading to decreased gluconeogenic gene expression and suppression of hepatic glucos..

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University of Melbourne Researchers

Magda Montgomery Author

Jacqueline Bayliss Author

Ayenachew Bezawork-Geleta Author

Matt Watt Author

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Grants

Awarded by Diabetes Australia Research Trust

Funding Acknowledgements

These studies were supported by funding from the National Health and Medical Research Foundation of Australia (APP1098972 to M.J.W. and APP1156508 to M.J.W. and G.R.S.) and the Diabetes Australia Research Trust. M.J.W. and M.K.M. are supported by Research Fellowships from the NHMRC (APP1077703 and APP1143224). L.A.S. is supported by a Principal Cancer Research Fellowship, awarded by Cancer Council's Beat Cancer project on behalf of its donors, the state Government through the Department of Health, and the Australian Government through the Medical Research Future Fund. R.C.R.M. is supported by a "Marie Sklodowska Curie individual fellowship" by the European Commission (H2020-MSCA-IF).