LOCALIZATION OF THE ATP-SENSITIVE K+ CHANNEL SUBUNIT KIR6.2 IN MOUSE PANCREAS

Kir6.2, a member of the inward rectifier K+ channel family, is a compo nent of the ATP-sensitive K+ (K-ATP) channel considered to play a key role in glucose-induced insulin secretion. We studied the distribution of Kir6.2 in mouse pancreas at the cellular level. The sites of Kir6. 2 mRNA expression were determined by in situ hybridization histochemis try with a digoxigenin (DIG)-labeled antisense cRNA probe. The hybridi zation signal was unevenly present throughout the islets of Langerhans , while no distinct signal was detected in exocrine acinar cells. This distribution was confirmed by another cRNA probe complementary to a d ifferent region of Kir6.2 mRNA. In situ hybridization and immunofluore scence staining of serial sections with the anti-insulin, the anti-glu cagon, and the anti-somatostatin antibodies showed Kir6.2 mRNA to be p resent in alpha-, beta-, and delta-cells. Furthermore, immunofluoresce nce staining with antibody raised against Kir6.2 revealed that Kir6.2 protein is localized within the pancreatic islets and is not found in exocrine pancreas. Kir6.2 was further shown to be located together wit h insulin, glucagon, or somatostatin. The positive staining of Kir6.2 appeared concentrated along the contour of each islet cell, suggesting that Kir6.2 is at the plasma membrane of islet cells. These results s uggest that Kir6.2, as a component of K-ATP channels, is an important molecule in the regulation of all the release of insulin, glucagon, an d somatostatin.