Trans-11 vaccenic acid improves glucose homeostasis in a model of type 2 diabetes by promoting insulin secretion via GPR40

It is largely unknown whether and how trans-11 vaccenic acid (VA), a ruminant trans-fatty acid with health benefits, influences glucose homeostasis in type 2 diabetes (T2D). VA was provided in diet to rats and in vitro to human/rat islets with diabetogenic challenges. Compared to rats with T2D induced by high-fat diet/streptozotocin, T2D + VA animals had improved ambient and fasting blood glucose, beta-cell area, in vivo insulin secretion, and ex vivo glucose-stimulated insulin secretion (GSIS) in islets from T2D + VA rats, which were accompanied with higher islet mRNA and protein expression of G-protein coupled receptor 40 (GPR40). In vitro, VA enhanced GPR40 protein expression and protein kinase Dl phosphorylation, and promoted GSIS in rat and human islets, an effect blocked by the inhibition of GPR40 and protein kinase D. These results indicate that VA may improve glycemic control by promoting insulin secretion in T2D, at least partly through stimulating GPR40 expression and signaling.