Age-dependent reduction in insulin secretion and insulin mrna in
isolated islets from rats.
Perfetti, Riccardo, Chahrzad Montrose Rafizadeh, Anthony S. Liotta,
and Josephine M. Egan.
Diabetes Unit, Laboratory of Clinical Physiology, Gerontology
Research Center, National Institute on Aging, National Institutes of
Health, Baltimore, MD 21224
APStracts 2:0153E, 1995.
Aging is an etiologic factor in non-insulin-dependent diabetes
mellitus. In order to characterize the [beta]-cell abnormalities
which occur with age, we investigated glucose-stimulated insulin
release, pancreatic insulin content and mRNA levels for islet
-specific genes in aging Wistar rats. Ten minutes after glucose
stimulation, 6-month-old islets had approximately 40% more cells
secreting insulin than 24-month-old islets (p<0.0001); after 1
hour 67+1.0% islets from 6-month-old rat secreted insulin, compared
to 51+3.5% from 24-month-old rat (p<0.0001). The amount of
insulin secreted by each [beta]-cell was also less in the older
animals (p<0.0001). Despite increases in islet size
(p<0.0001) and in [beta]-cell number (p<0.0001) with age,
whole pancreas insulin content showed that 24-month-old pancreas had
less insulin than 6-month-old pancreas (0.61+ 0.06 vs. 0.84 + 0.08
[mu]g/mg pancreatic protein; p<0.05). Finally, insulin mRNA
levels declined to 50% of the newborn value in 24-month-old islets
(p<0.0001), while glucagon mRNA levels showed a very modest
decline with age. Somatostatin mRNA levels did not vary
significantly. In summary, it appears that in Wistar rats there is a
progressive decline in [beta]-cell activity with age. This decline
may represent the biological features of the age-dependent risk of
developing diabetes.
Received 7 February 1995; accepted in final form 23 June 1995.
APS Manuscript Number E56-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.