Laboratory Investigation

Kidney International (1991) 40, 413–417; doi:10.1038/ki.1991.227

Impaired potassium-induced insulin secretion in chronic renal failure

George Z Fadda1, Prasert Thanakitcharu1, Roderick Comunale1, Loren G Lipson1 and Shaul G Massry1

1Department of Medicine, Division of Nephrology, University of Southern California School of Medicine, Los Angeles, California, USA

Correspondence: Shaul G Massry MD, Department of Medicine, Division of Nephrology, University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, California 90033, USA.

Received 7 February 1991; Revised 15 April 1991; Accepted 16 April 1991.

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Abstract

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 < 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 < 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. The data indicate that: 1) K+-induced insulin secretion in islets of CRF is impaired, most likely, due to elevated basal level of [Ca2+]i and reduced calcium signal and/or smaller Delta[Ca2+]i/basal [Ca2+]i ratio in response to KCl; 2) the defect in K+-induced insulin secretion may contribute to the impaired extrarenal potassium disposal in CRF; and 3) the abnormalities in pancreatic islets may be mediated by the chronic excess of PTH in CRF.

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