AJP - Renal Physiology, Vol 259, Issue 2 210-F216, Copyright © 1990 by American Physiological Society
Mechanisms of impaired insulin secretion after chronic excess of parathyroid hormone
A. F. Perna, G. Z. Fadda, X. J. Zhou and S. G. Massry
Division of Nephrology, University of Southern California School of Medicine, Los Angeles 90033.
Excess parathyroid hormone (PTH) in presence or absence of chronic renal
failure impairs insulin release from pancreatic islets. This abnormality
has been attributed to PTH-induced accumulation of Ca in the cytosol of the
islets. Direct evidence for the latter phenomenon is lacking. This study
examined the effect of chronic administration of PTH to rats with normal
renal function on resting cytosolic Ca of the islets and evaluated the
mechanisms through which a rise in resting cytosolic Ca may inhibit insulin
secretion. After 42 days of PTH administration, glucose-induced insulin
secretion was impaired, and this defect was corrected by the use of
D-glyceraldehyde as secretagogue for insulin. Resting cytosolic Ca of
islets from PTH-treated rats was markedly increased compared with that of
islets from normal animals (288 +/- 27.1 vs. 135 +/- 3.7 nM, P less than
0.01), and their content of ATP in the presence of both 2.8 and 16.7 mM
D-glucose was reduced (2.8 mM D-glucose, 4.6 +/- 0.17 vs. 6.0 +/- 0.42
pmol/islet, P less than 0.01; and 16.7 mM D-glucose, 6.9 +/- 0.25 vs. 11.1
+/- 0.95 pmol/islet, P less than 0.01). D-Glyceraldehyde increased ATP
content in islets of PTH-treated rats from 4.6 +/- 0.17 to 8.8 +/- 0.71
pmol/islet. Glucose uptake by the islets, their insulin content, and both
the Vmax and the apparent Km for fructose 6-phosphate of
phosphofructokinase 1 (EC 2.7.1.11) in PTH-treated rats were not different
from normal. The two major cellular derangements in the islets of
PTH-treated rats were a reduction in ATP content and a rise in resting
cytosolic Ca.(ABSTRACT TRUNCATED AT 250 WORDS)
