Immuno-localization of sulphonylurea receptor 1 in rat pancreas.
OBJECTIVE
A sulphonylurea receptor, SUR1, and an inward rectifier potassium channel, Kir6.2, reconstitute the ATP-sensitive K(+) channel that mediates glucose-induced insulin secretion in pancreatic beta cells. We reported previously that Kir6.2 were localized at insulin-, glucagon-, and somatostatin-producing cells. In this new study we aimed to determine the distribution of SUR1 in rat pancreatic islets and to suggest the location of the ATP-sensitive K(+) channels in the islet.


METHODS
Western blot analysis was carried out using two anti-SUR1 antibodies, which had been raised against different portions of rat SUR1. SUR1, Kir 6.2, and islet hormones were then localized by indirect immunofluorescence staining of the cryosections of rat pancreas.


RESULTS
In Western blot analysis, each of the anti-SUR1 antibodies detected a band at 140 kDa, which is close to the predicted molecular weight of SUR1, in the homogenate of isolated pancreatic islets. Double immunofluorescence staining of cryosections showed that SUR1 occurred all over the islets, and that SUR1 colocalized with insulin, glucagon, somatostatin, and pancreatic polypeptide. Kir6.2 was also shown to be present in pancreatic polypeptide cells.


CONCLUSIONS
Together with our previously reported data, the above findings indicate that K(ATP) channels comprising SUR1 and Kir6.2 occur not only in beta cells but also in the alpha, delta, and pancreatic polypeptide cells of the pancreatic islets, suggesting that therapeutic sulphonylureas could act on these cells directly. [Diabetologia (1999) 42: 1204-1211]
Suzuki
M
M
Laboratory of Molecular and Cellular Morphology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan.
Fujikura
K
K
Kotake
K
K
Inagaki
N
N
Seino
S
S
Takata
K
K
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D000918:Antibody Specificity; D005934:Glucagon / Q000378:metabolism; D051273:Glucose Transporter Type 2; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000378:metabolism; D015221:Potassium Channels / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D011955:Receptors, Drug / Q000096:biosynthesis* / Q000276:immunology; D064233:Sulfonylurea Receptors; D014018:Tissue Distribution
D018528:ATP-Binding Cassette Transporters; C577509:Abcc8 protein, rat; D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D010191:Pancreatic Polypeptide; D005934:Glucagon