Mitochondrial transhydrogenase--a key enzyme in insulin secretion and, potentially, diabetes

Abstract

Two recent studies have shown that the glucose intolerance and impaired insulin secretion of the C57BL/6J mouse strain results from oxidative stress due to a mutated nicotinamide nucleotide transhydrogenase. Reproduction of this phenotype, by mutating the same enzyme in another strain with normal glucose tolerance, suggests that the mechanism of the transhydrogenase-dependent inhibition of insulin secretion involves a partial uncoupling by the UCP2 protein. These exciting findings raise important questions, not least their potential relevance for human diabetes.