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.