Human Islets of Langerhans Express Multiple Isoforms of Calcium/Calmodulin-Dependent Protein Kinase II

Previous studies have provided evidence for the presence of calcium/calmodulin-dependent protein kinase II (CaM kinase II) in rodent islets of Langerhans, and β-cell CaM kinase II activity has been correlated with insulin secretion. In this study we provide the first conclusive evidence for the expression of CaM kinase II in human islets of Langerhans and show that multiple isoforms are expressed. Screening of a human islet cDNA library resulted in the isolation of a 999bp partial cDNA clone encoding CaM kinase II. The nucleotide sequence of the islet clone showed a high degree of homology (94.8%) to the two γ isoforms of CaM kinase II previously isolated from human T lymphocytes (γBand γC). In order to obtain full length sequence for the islet clone, rapid amplification of cDNA ends (RACE) was used to amplify the 3′ end of the islet clone from human islet poly A+RNA. Two distinct γ isoforms of CaM kinase II were amplified from the islet RNA. They were identified as γBand γE; the latter is distinguished from γBby a 114bp insertion within the association domain of the cDNA. Using reverse transcriptase polymerase chain reaction (RT-PCR) we also detected in human islets of Langerhans the novel β3isoform of CaM kinase II previously reported to be expressed in neonatal rat islets.