The C57BL/6J mouse displays glucose intolerance and reduced insulin secretion. The genetic locus underlying this phenotype was mapped to nicotinamide nucleotide transhydrogenase (Nnt) on mouse chromosome 13, a nuclear-encoded mitochondrial protein involved in beta-cell mitochondrial metabolism. C57BL/6J mice have a naturally occurring in-frame five-exon deletion in Nnt that removes exons 7-11. This results in a complete absence of Nnt protein in these mice. We show that transgenic expression of the entire Nnt gene in C57BL/6J mice rescues their impaired insulin secretion and glucose-intolerant phenotype. This study provides direct evidence that Nnt deficiency results in defective insulin secretion and inappropriate glucose homeostasis in male C57BL/6J mice.

Original publication

DOI

10.2337/db06-0358

Type

Journal article

Journal

Diabetes

Publication Date

07/2006

Volume

55

Pages

2153 - 2156

Keywords

Animals, Blood Glucose, Chromosomes, Artificial, Bacterial, Exons, Glucose Intolerance, Insulin, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, NADP Transhydrogenases, Quantitative Trait Loci, Sequence Deletion