Reduced activity of Na(+)-K+ ATPase of pancreatic islets in chronic renal failure: role of secondary hyperparathyroidism.
The activity of Na(+)-K+ ATPase of pancreatic islets modulates their insulin secretion. The study presented here examined the activity of this enzyme in pancreatic islets of chronic renal failure (CRF) rats in an effort to further delineate the mechanisms of impaired insulin secretion in CRF. The Vmax of Na(+)-K+ ATPase, but not its Km, and the ATP content are significantly reduced in islets of CRF rats that have elevated levels of parathyroid hormone (PTH). These derangements are prevented by prior parathyroidectomy of CRF rats (low blood levels of PTH) or by their treatment with the calcium channel blocker verapamil; these latter rats have sustained elevation of blood levels of PTH. The data indicate that the chronic excess blood levels of PTH in CRF initiates events (augmented entry of calcium) that lead to the reduction in ATP content and in Vmax of Na(+)-K+ ATPase of pancreatic islets. Reducing the blood levels of PTH by parathyroidectomy or blocking the action of PTH on calcium entry into cells by verapamil prevents these derangements. The results suggest that chronic inhibition of Na(+)-K+ ATPase may participate in the processes underlying the impaired insulin secretion in CRF.
Hajjar
S M
SM
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
Fadda
G Z
GZ
Thanakitcharu
P
P
Smogorzewski
M
M
Massry
S G
SG
D000818:Animals; D002118:Calcium / Q000502:physiology; D006962:Hyperparathyroidism, Secondary / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology* / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D007328:Insulin; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium