Complement 1q-like-3 protein inhibits insulin secretion from pancreatic -cells via the cell adhesion G protein– coupled receptor BAI3

Academic Article

Abstract

  • © 2018 American Society for Biochemistry and Molecular Biology Inc. All Rights Reserved. Secreted proteins are important metabolic regulators in both healthy and disease states. Here, we sought to investigate the mechanism by which the secreted protein complement 1q-like-3 (C1ql3) regulates insulin secretion from pancreatic -cells, a key process affecting whole-body glucose metabolism. We found that C1ql3 predominantly inhibits exendin-4 – and cAMP-stimulated insulin secretion from mouse and human islets. However, to a lesser extent, C1ql3 also reduced insulin secretion in response to KCl, the potassium channel blocker tolbutamide, and high glucose. Strikingly, C1ql3 did not affect insulin secretion stimulated by fatty acids, amino acids, or mitochondrial metabolites, either at low or submaximal glucose concentrations. Additionally, C1ql3 inhibited glucose-stimulated cAMP levels, and insulin secretion stimulated by exchange protein directly activated by cAMP-2 and protein kinase A. These results suggest that C1ql3 inhibits insulin secretion primarily by regulating cAMP signaling. The cell adhesion G protein–coupled receptor, brain angiogenesis inhibitor-3 (BAI3), is a C1ql3 receptor and is expressed in -cells and in mouse and human islets, but its function in -cells remained unknown. We found that siRNA-mediated Bai3 knockdown in INS1(832/13) cells increased glucose-stimulated insulin secretion. Furthermore, incubating the soluble C1ql3-binding fragment of the BAI3 protein completely blocked the inhibitory effects of C1ql3
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Gupta R; Nguyen DC; Schaid MD; Lei X; Balamurugan AN; Wong GW; Kim JA; Koltes JE; Kimple ME; Bhatnagar S
  • Start Page

  • 18086
  • End Page

  • 18098
  • Volume

  • 293
  • Issue

  • 47