CLONING OF RAT K(ATP)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, K-ATP-2, whose sequence shows 72% identity with the rat heart potassium channel K-ATP. RNA blotting sho wed that K-ATP-2 mRNA was present at high levels in brain and undetect able 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 K-ATP-2 mRNA per microgram of total RNA in pancreat ic islets from nondiabetic rats. The levels of K-ATP-2 mRNA were reduc ed by 34% in islets from diabetic Zucker diabetic fatty male rats, a m odel of non-insulin dependent diabetes mellitus, compared to their lea n nondiabetic littermates (p < 0.05),suggesting that decreased express ion of K-ATP-2 may contribute to beta-cell dysfunction in this animal model. (C) 1995 Academic Press, Inc.