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https://hdl.handle.net/2440/128313
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Type: | Journal article |
Title: | SMOC1 is a glucose-responsive hepatokine and therapeutic target for glycemic control |
Author: | Montgomery, M.K. Bayliss, J. Devereux, C. Bezawork-Geleta, A. Roberts, D. Huang, C. Schittenhelm, R.B. Ryan, A. Townley, S.L. Selth, L.A. Biden, T.J. Steinberg, G.R. Samocha-Bonet, D. Meex, R.C.R. Watt, M.J. |
Citation: | Science Translational Medicine, 2020; 12(559):1-13 |
Publisher: | American Association for the Advancement of Science |
Issue Date: | 2020 |
ISSN: | 1946-6234 1946-6242 |
Statement of Responsibility: | Magdalene K. Montgomery, Jacqueline Bayliss, Camille Devereux, Ayenachew Bezawork-Geleta ... Scott L. Townley, Luke A. Selth ... et al. |
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 glucose output. Overexpression of SMOC1 in the liver or once-weekly intraperitoneal injections of a stabilized SMOC1-FC fusion protein induced durable improvements in glucose tolerance and insulin sensitivity in db/db mice, without adverse effects on adiposity, liver histopathology, or inflammation. Furthermore, circulating SMOC1 correlated with hepatic and systemic insulin sensitivity and was decreased in obese, insulin-resistant humans. Together, these findings identify SMOC1 as a potential pharmacological target for the management of glycemic control in type 2 diabetes. |
Keywords: | Liver Animals Mice, Inbred C57BL Mice Diabetes Mellitus, Type 2 Insulin Resistance Insulin Glucose Blood Glucose Glycemic Control |
Rights: | © 2020, Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. https://www.sciencemag.org/about/science-licenses-journal-article-reuseThis is an article distributed under the terms of the Science Journals Default License. |
DOI: | 10.1126/scitranslmed.aaz8048 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1156508 http://purl.org/au-research/grants/nhmrc/1098972 http://purl.org/au-research/grants/nhmrc/1077703 http://purl.org/au-research/grants/nhmrc/1143224 http://purl.org/au-research/grants/nhmrc/1077703 http://purl.org/au-research/grants/nhmrc/1143224 |
Published version: | http://dx.doi.org/10.1126/scitranslmed.aaz8048 |
Appears in Collections: | Aurora harvest 8 Environment Institute publications |
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