Pathogenesis of type 2 diabetes in Japan and East Asian populations: Basic and clinical explorations.

It is now accepted that the pathogenesis of type 2 diabetes in East Asians including Japanese differs distinctly from that in Caucasians. Many non-obese individuals in Japan develop type 2 diabetes and present clinically with insufficient insulin secretion rather than a large increase in the insulin resistance. To understand the pathophysiology of this non-obese diabetes, we studied Goto-Kakizaki rats, a unique model of spontaneous non-obese diabetes, and identified mitochondrial dysfunction in pancreatic β-cells as a factor in decreased insulin secretion. Looking for a clinical treatment option, we focused on the incretins because of their glucose-dependent insulin stimulatory effect. Our findings have contributed to the understanding of incretin action and the development of incretin-associated therapeutics and shed light on the nature of East Asian diabetes and its optimal clinical treatment.