Decreased mitochondrial gene expression in isolated islets of rats injected neonatally with streptozotocin.

The aim of the present study was to evaluate the possible role of the expression of the mitochondrial genome for the regulation of insulin production in the pancreatic Beta cell. For this purpose, islets of Langerhans were isolated from adult control rats and rats injected neonatally with streptozotocin and the islet contents of specific mitochondrial DNAs and RNAs together with nuclear-encoded RNAs were determined. The contents of mitochondrial cytochrome b mRNA, the mitochondrial 12 S rRNA and insulin mRNA were all 30-40% lower in islets isolated from the streptozotocin-treated rats as compared to islets from control rats. In contrast, the nuclear mRNA coding for the mitochondrial adenine nucleotide translocator was not decreased in the streptozotocin-treated rats. Contents of mitochondrial DNA, as assessed by the Southern blotting technique, were markedly decreased in the streptozotocin islets. Sequence analysis of mitochondrial DNA from streptozotocin islets and control islets however, did not reveal any differences in nucleotide sequences. In control islets the contents of mitochondrial cytochrome b mRNA increased in response to a high glucose concentration during a 4-h incubation period. Serum deprivation or the addition of theophylline or 4-phorbol 12-myristate 13-acetate failed to affect the cytochrome b mRNA contents in vitro. It is concluded that islets of streptozotocin-treated rats contain low contents of mitochondrial DNA and RNA. Since a lower mitochondrial RNA content may result in a diminished oxidative capacity, it is conceivable that a deficiency of this messenger may contribute to the development of insulin deficiency.