ATP-sensitive potassium channel (KATP channel) expression in the normal canine pancreas and in canine insulinomas

Pancreatic beta cells express ATP-sensitive potassium (KATP) channels that are needed for normal insulin secretion and are targets for drugs that modulate insulin secretion. The KATP channel is composed of two subunits: a sulfonylurea receptor (SUR 1) and an inward rectifying potassium channel (Kir6.2). KATP channel activity is influenced by the metabolic state of the cell and initiates the ionic events that precede insulin exocytosis. Although drugs that target the KATP channel have the expected effects on insulin secretion in dogs, little is known about molecular aspects of this potassium channel. To learn more about canine beta cell KATP channels, we studied KATP channel expression by the normal canine pancreas and by insulin-secreting tumors of dogs.

Pancreatic tissue from normal dogs and tumor tissue from three dogs with histologically-confirmed insulinomas was examined for expression of KATP channel subunits (SUR1 and Kir6.2) using RT-PCR. Normal canine pancreas expressed SUR1 and Kir6.2 subunits of the KATP channel. The partial nucleotide sequences for SUR1 and Kir6.2 obtained from the normal pancreas showed a high degree of homology to published sequences for other mammalian species. SUR1 and Kir6.2 expression was observed in each of the three canine insulinomas examined. Comparison of short sequences from insulinomas with those obtained from normal pancreas did not reveal any mutations in either SUR1 or Kir6.2 in any of the insulinomas.

Canine pancreatic KATP channels have the same subunit composition as those found in the endocrine pancreases of humans, rats, and mice, suggesting that the canine channel is regulated in a similar fashion as in other species. SUR1 and Kir6.2 expression was found in the three insulinomas examined indicating that unregulated insulin secretion by these tumors does not result from failure to express one or both KATP channel subunits.