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Original Contribution

The Nature of Insulin Secretory Defect in Aging Rats

  1. Boris Draznin,
  2. Jay P Steinberg,
  3. J Wayne and
  4. Karl E Sussman
  1. Medical Service, the Veterans Administration Medical Center, and the Department of Medicine, University of Colorado School of Medicine Denver, Colorado
  1. Address reprint requests to Boris Draznin, M.D., VA Medical Center, 1055 Clermont St., Denver Colorado 80220.
Diabetes 1985 Nov; 34(11): 1168-1173. https://doi.org/10.2337/diab.34.11.1168
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Abstract

We have attempted to define the nature of insulin secretory defect(s) in aged animals. In these studies, pancreatic islets were isolated from 2- and 18-mo-old Fischer 344 rats. Margination of secretion vesicles during exocytosis was assessed by measuring the recruitment of somatostatin (SRIF) receptors to the surface membrane. Section vesicle lysis was studied by measuring insulin release into the incubation media.

Submaximal and maximal glucose-induced insulin secretion was significantly greater in islets isolated from younger rats (P < 0.01). SRIF recePtor recruitment was stimulated by glucosein both younger and older Fischer 344 rats. However, an increase in SRIF receptor recruitment wasreduced in islets isolated from older animals (from 2.14 ± 0.4 to 4.6 ± 0.4 fmol/10 islets) (P < 0.01) as compared with islets from younger animals (from 2.6 ± 0.2 to 6.2 ± 0.4 fmol/10 islets). When secretion vesicle lysis was inhibited by the presence of sodium isethionate in the incubation media, glucose (300 mg/dl) failed to stimulate secretion vesicle margination to the plasma membrane. In contrast, glyburide (0.6 μg/ml) continued to stimulate directly secretion vesicle margination in islets from aged animals (from 2.1 ± 0.3 to 6.0 ± 0.3 fmol/10 islets).

We conclude that glucose-induced margination of secretion vesicles at the plasma membrane is impaired by the aging process. This impairment results in lower submaximal and maximal insulin secretory response to glucose. The fact that glyburide is capable of stimulating secretion vesicle margination suggests that glucose signal recognition and/or stimulus-secretion coupling may be the locus of impairment in the process of insulin secretion in older animals.

  • Received December 18, 1984.
  • Revision received June 10, 1985.
  • Copyright © 1985 by the American Diabetes Association
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November 1985, 34(11)
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The Nature of Insulin Secretory Defect in Aging Rats
Boris Draznin, Jay P Steinberg, J Wayne, Karl E Sussman
Diabetes Nov 1985, 34 (11) 1168-1173; DOI: 10.2337/diab.34.11.1168

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The Nature of Insulin Secretory Defect in Aging Rats
Boris Draznin, Jay P Steinberg, J Wayne, Karl E Sussman
Diabetes Nov 1985, 34 (11) 1168-1173; DOI: 10.2337/diab.34.11.1168
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