miR-204 Controls Glucagon-Like Peptide 1 Receptor Expression and Agonist Function

• DOI: 10.2337/db17-0506
• Publication Date: 2017-11-04T00:25:33Z
• Authors: SeongHo Jo; Junqin Chen; Guanlan Xu; Truman B. Grayson; Lance A. Thielen; Anath Shalev
• Keywords: Male; Mice, Knockout; 0301 basic medicine; Glucagon-Like Peptide-1 Receptor; Diabetes Mellitus, Experimental; Mice, Inbred C57BL; MicroRNAs; 03 medical and health sciences; HEK293 Cells; Gene Expression Regulation; Genes, Reporter; Cell Line, Tumor; Insulin-Secreting Cells; Insulin Secretion; Mutation; Animals; Humans; Hypoglycemic Agents; Insulin; RNA; 3' Untranslated Regions; Cells, Cultured

Glucagon-like peptide 1 receptor (GLP1R) agonists are widely used to treat diabetes. However, their function is dependent on adequate GLP1R expression, which downregulated in highly expressed pancreatic β-cells, and activation by endogenous incretin or increases cAMP generation, stimulates glucose-induced β-cell insulin secretion helps maintain glucose homeostasis. We now have discovered that the β-cell–enriched microRNA, miR-204, directly targets 3′ UTR of thereby downregulates its expression β-cell–derived rat INS-1 cell line primary mouse human islets. Furthermore, vivo deletion miR-204 promoted islet enhanced responsiveness agonists, resulting improved tolerance, production, as well protection against Since we recently identified thioredoxin-interacting protein (TXNIP) an upstream regulator also assessed whether TXNIP could mimic miR-204. Indeed, it agonist–induced tolerance. Thus, present studies show for first time under control a uncover previously unappreciated link between action.