Insulin release from pancreatic islets: Effects of CRF and excess PTH

Abstract

Insulin secretion may be impaired in chronic renal failure (CRF) and available data suggest that this abnormality may be related to the state of secondary hyperparathyrodism of renal failure. We directly measured insulin release from isolated islets of Langerhans obtained from normal rats, CRF-control and CRF-PTX (parathyroidectomized) rats, and parathyroid hormone (PTH)-treated animals. Both early and total glucose-induced insulin release from islets of CRF-control were markedly and significantly (P < 0.01) lower than from islets of normal rats. Insulin release from islets of CRF-PTX rats was significantly (P < 0.01) higher than that from islets of CRF-control rats, and not different from insulin release from islets of normal rats. Forskolin and IBMX, which cause a rise in cAMP, significantly stimulated glucose-induced insulin release from islets of normal, CFR-control and CRF-PTX rats, but the increments from baseline were not significantly different between the three groups. Both early and total insulin release from islet obtained from PTH-treated rats with normal renal function were markedly and significantly (P < 0.01) lower than values obtained from normal rats. Calcium contents of the pancreas of CRF-control and PTH-treated rats were significantly (P < 0.01) higher than that in pancreas of normal rats and CRF-PTX animals, and values in the latter two groups of animals were not significantly different. The results show that: 1) CRF impairs insulin release from pancreatic islets; 2) this abnormality is reversed by prior parathyroidectomy; and 3) hyperparathyroidism induced by PTH-treatment in normal rats impairs insulin release from pancreatic islets. The data provide a direct evidence for the role of secondary hyperparathyroidism in the genesis of abnormal carbohydrate metabolism in CRF. This effect of excess PTH is not related to alterations in cAMP production but may potentially be due to calcium accumulation in the pancreas.