Islets From Prediabetic Db/Db Mice Show Enhanced Susceptibility To Cytokine-Mediated Dysfunction

Pancreatic islets secrete insulin and other hormones to regulate blood glucose. A key component of Type 2 Diabetes (T2D) is islet dysfunction. In these studies, we examined whether cytokines at concentrations associated with low-grade systemic inflammation lead to islet dysfunction. We examined islets from 5-week-old db/db mice (prior to obesity or elevated blood glucose) and age-matched, non-diabetic, heterozygous controls for physiological signs of islet dysfunction after overnight cytokine treatment. Glucose-stimulated increases in calcium influx and insulin release were at least as robust in untreated islets from db/db mice as from controls, suggesting that islet function is not yet impaired in db/db mice. When cultured overnight with 10 pg/ml IL-1B + 20 pg/ml IL-6, however, responses to glucose stimulation were inhibited to a much greater degree in islets from db/db mice as compared to controls. At higher concentrations, these cytokines increased cell death, but only in islets from the db/db mice. Our findings suggest that low-grade systemic inflammation triggers islet dysfunction in T2D and that novel techniques for reducing inflammation may help in preventing T2D. Supported by NIH K01DK081621.