A direct look at the dysfunction and pathology of the β cells in human type 2 diabetes

β cells uniquely produce and secrete insulin under the control of several, integrated signals, to maintain blood glucose concentrations within a narrow physiological interval. β cell failure is key to the onset and progression of type 2 diabetes, due to impaired function and reduced mass. In this review we focus on several features of human β cell dysfunction and pathology in type 2 diabetes, as revealed by direct assessment of isolated islet traits and examination of pancreatic tissue from organ donors, surgical samples or autoptic specimens. Insulin secretion defects and pathology findings are discussed in relation to some of the major underlying mechanisms, to also provide clues for conceiving better prevention and treatment of type 2 diabetes by targeting the pancreatic β cells.