EXPRESSION OF CD38 GENE, BUT NOT OF MITOCHONDRIAL GLYCEROL-3-PHOSPHATE DEHYDROGENASE GENE, IS IMPAIRED IN PANCREATIC-ISLETS OF GK RATS

Goto-Kakizaki (GK) rat, a rodent model of spontaneously occurring non- insulin dependent diabetes mellitus (NIDDM), exhibits impaired glucose -stimulated insulin secretion. To explore the background of the beta-c ell dysfunction in NIDDM, we investigated whether and how the expressi on pattern of factors that would potentially be involved in the glucos e-stimulated insulin secretion machinery is changed in GK rats. Using quantitative reverse transcription-PCR (RT-PCR) method, we found that the gene expression of CD38, a type 2 membrane protein which has ADP-r ibosyl cyclase activity, is reduced by approximately 50% in islets of GK rats. Despite previous studies showing reduction in the FAD-linked mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) activity in G K rats, the mGPDH mRNA amounts were equal to those in the control Wist ar rats, suggesting a difference that arose post-transcriptionally. Th ese observations support the idea that multiple defects of the glucose -responsive insulin secreting machinery are involved in the developmen t of diabetes in GK rats. (C) 1995 Acidemic Press, Inc.