Correction of glucose intolerance and the impaired insulin release of chronic renal failure by verapamil

• Published in: Kidney international Vol. 36; no. 5; pp. 773 - 779
• Main Authors: Fadda, George Z., Akmal, Mohammad, Soliman, Amin R., Lipson, Loren G., Massry, Shaul G.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-11-1989; Nature Publishing
• Subjects: Animals; Biological and medical sciences; Calcium Channels - metabolism; Glucose - metabolism; Hormones. Endocrine system; Hyperparathyroidism, Secondary - etiology; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - metabolism; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - physiopathology; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Verapamil - therapeutic use; Endocrinopathy; Pancreatic hormone; Urinary system disease; Rat; Rodentia; Calcium antagonist; Insulin; Protein hormone; Vertebrata; Chemotherapy; Chronic; Experimental disease; Mammalia; Treatment; Animal; Renal failure; Subcutaneous administration; Hormonal investigation; Impaired glucose tolerance; Hyperparathyroidism
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.1989.262

Correction of glucose intolerance and the impaired insulin release of chronic renal failure by verapamil. Insulin release from pancreatic islets is impaired in chronic renal failure (CRF), and this is due to the state of secondary hyperparathyroidism of CRF. This defect in association with resistance to the peripheral action of insulin-caused glucose intolerance in CRF. It has been suggested that the impaired insulin release induced by excess parathyroid hormone (PTH) is related to the ability of the hormone to augment calcium entry into the pancreatic islets, resulting in accumulation of calcium in the pancreas. Therefore, a calcium channel blocker may antagonize this effect of PTH, and hence normalize glucose tolerance in CRF. The present study examined this postulate by studying intravenous glucose tolerance and insulin release from pancreatic islets in normal and CRF rats and in CRF animals treated with the calcium channel blocker, verapamil. Rats with 42 days of CRF displayed impaired glucose tolerance, significant reduction (P < 0.01) in insulin release by islets, and doubling of calcium content of the pancreas (P < 0.01) as compared to normal rats. Simultaneous treatment of CRF rats with verapamil for 42 days resulted in normal glucose tolerance, higher blood insulin levels during glucose infusion, normal calcium content of the pancreas, and normal insulin secretion by the islets. Treatment of normal rats with verapamil for 42 days did not affect any of the parameters studied. The results show that the calcium channel blocker, verapamil, by preventing calcium accumulation in the pancreas, reversed the abnormalities in insulin release that occur in CRF. This effect allowed a greater rise in blood levels of insulin during glucose infusion in CRF rats. These higher levels of insulin overcame the peripheral resistance to its action, and hence normalized glucose tolerance in CRF.