Cloning of rat KATP-2 channel and decreased expression in pancreatic islets of male Zucker diabetic fatty rats.

ATP-regulated potassium channels play a key role in regulating insulin secretion. We have isolated cDNA clones from a RINm5F insulinoma cell cDNA library that encode a protein, KATP-2, whose sequence shows 72% identity with the rat heart potassium channel KATP. RNA blotting showed that KATP-2 mRNA was present at high levels in brain and undetectable in heart, spleen, lung, liver, skeletal muscle, kidney and testis. A quantitative RT-PCR assay indicated that there were 1.85 +/- 0.32 x 10(5) molecules of KATP-2 mRNA per microgram of total RNA in pancreatic islets from nondiabetic rats. The levels of KATP-2 mRNA were reduced by 34% in islets from diabetic Zucker diabetic fatty male rats, a model of non-insulin dependent diabetes mellitus, compared to their lean nondiabetic littermates (p < 0.05), suggesting that decreased expression of KATP-2 may contribute to beta-cell dysfunction in this animal model.