Impaired potassium-induced insulin secretion in chronic renal failure.
Extrarenal disposal of potassium load is impaired in chronic renal failure (CRF). This has been attributed to excess PTH since extrarenal disposition of potassium is normal in CRF-PTX animals. Insulin augments potassium entry into cells and hyperkalemia stimulates insulin secretion. Since glucose-induced insulin secretion is impaired in CRF and normal in CRF-PTX, it is possible that K(+)-induced insulin secretion is also impaired in CRF due to excess PTH. Such a defect would contribute to the abnormality in extrarenal disposal of potassium in CRF. We examined K(+)-induced insulin secretion, cytosolic calcium ([Ca2+]i) and the changes in [Ca2+]i in response to 20 mM KCl of islets from normal, CRF, and CRF-PTX rats; and normal and CRF animals treated with verapamil (normal-V and CRF-V). K(+)-induced insulin secretion by islets isolated from CRF rats was significantly (P less than 0.01) lower than that from normal, CRF-PTX, CRF-V and normal-V rats. Basal level of [Ca2+]i in islets of CRF rats was significantly (P less than 0.01) higher than in islets of the other four groups of animals. The calcium signal (delta [Ca2+]i) and the delta [Ca2+]i/basal [Ca2+]i ratio in response to 20 mM KCl observed in islets from CRF rats were significantly lower than in the other four groups of animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Fadda
G Z
GZ
Department of Medicine, University of Southern California School of Medicine, Los Angeles.
Thanakitcharu
P
P
Comunale
R
R
Lipson
L G
LG
Massry
S G
SG
D000818:Animals; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D008297:Male; D010281:Parathyroid Hormone / Q000378:metabolism; D010758:Phosphorus / Q000097:blood; D011188:Potassium / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects; D015398:Signal Transduction
D007328:Insulin; D010281:Parathyroid Hormone; D010758:Phosphorus; D003404:Creatinine; D011188:Potassium; D002118:Calcium