Year: 2013
Type: article
Abstract: Impairments in insulin secretion and action are the pathophysiological hallmarks of type 2 diabetes (1,2). Pharmacological approaches to restore β-cell function have led to the use of insulin secretagogues that include sulphonylureas, glinides, and glucagon-like peptide-1–based therapies. Of these, the latter hold particular clinical advantage because glucagon-like peptide-1–modulated insulin secretion is glucose dependent (3,4), thereby minimizing the risk for hypoglycemia—the bane of clinicians managing diabetes across the world.
Fatty acids have long been known (5) to modulate human β-cell function. While acutely fatty acids amplify glucose-stimulated insulin secretion, chronic elevation of free fatty acid (FFA) levels has been thought to inhibit insulin secretion through the phenomenon of “lipotoxicity” (6,7). The cellular/molecular intermediates that are involved in this complex modulation, elegantly summarized in ref. 5, include malonyl CoA/long-chain acyl-CoA, triglyceride/FFA cycling through diacylglycerol, G-protein–coupled receptor 40 (GPR40) and phospholipase A2.
G-protein–coupled receptors have recently emerged as novel therapeutic targets because they appear to be closely involved in the pathology of various metabolic disorders including obesity, dyslipidemia, and type 2 diabetes (8). Since the seminal article (9) in 2003 about the role of GPR40 (also known as FFA1R: free fatty acid 1 receptor) in long-chain fatty acid–mediated glucose-stimulated insulin secretion from rodent and human β-cells, there have been over 60 publications investigating the properties and modulators of this receptor as yet another potential therapeutic approach for the management of type 2 diabetes. GPR40 is expressed most abundantly in humans in pancreatic β-cells …
Source: Diabetes Care
DOI: 10.2337/dc12-1721
Authors: Ananda Basu, Yogish C. Kudva, Rita Basu
Institution: Mayo Clinic
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W2158383652