The ABCs of beta-cell dysfunction in type 2 diabetes.

摘要

Entia non sunt multiplicanda praeter necessitatem-entities should not be multiplied beyond necessity, or, the simplest solution is best. This dictum, commonly attributed to the 14th century English philosopher William of Occam, is sometimes invoked to explain disparate observations in medicine. Diabetes, for instance, is characterized by both high blood sugar and dyslipidemia, consisting of elevated triglycerides and decreased high-density lipoprotein (HDL)-leading to atherosclerosis, the most common cause of death in diabetes. The final common pathway in the pathogene-sis of type 2 diabetes, however, is the failure of beta-cells in the pancreas, which occurs when they can no longer sustain insulin hypersecretion in the setting of insulin resistance. In this issue, Brunham et al. identify intracellular cholesterol as a potential pathogenetic link between type 2 diabetes and coronary heart disease. Their findings raise the tantalizing possibility of targeting a single pathway to protect both the beta-cell and the vasculature. Lipids, especially saturated fatty acids, may perturb the function of beta-cells by altering intracellular calcium signaling and generating ceramide, which induces apoptosis. Brunham et al. tested the hypothesis that cholesterol homeostasis is also important in the beta-cell.