SUMMARY We hypothesized that the known heterogeneity of pancreatic β cells was due to subpopulations of β cells at different stages of their lifecycle with different functional capacities and that further changes occur with metabolic stress and aging. We identified new markers of aging in β cells, including IGF1R. In β cells IGF1R expression correlated with age, dysfunction and with expression of known age markers p16ink4a, p53BP1 and senescence-associated β-galactosidase. The new markers showed striking heterogeneity both within and between islets in both mouse and human pancreas. Acute induction of insulin resistance with an insulin receptor antagonist or chronic ER stress resulted in increased expression of aging markers, providing insight into how metabolic stress might accelerate dysfunction and decline of β cells. These novel findings about β-cell and islet heterogeneity, and how they change with age, open up an entirely new set of questions about the pathogenesis of type 2 diabetes.

Bromine incorporation into the skutterudite structure simultaneously lowers the thermal conductivity, tunes the carrier concentration, and preserves the high mobility of the native compound.

Experimental and computational investigation of the phase stability and thermoelectric properties of the Co4Sn6Te6 skutterudite.