Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 51, Issue 5 B331-B336, Copyright © 1996 by The Gerontological Society of America
Molecular investigation of age-related changes in mouse endocrine pancreas
R Perfetti, Y Wang, AR Shuldiner and JM Egan
Diabetes Unit, Laboratory of Clinical Physiology, National Institute on Aging, National Institutes of Health, Baltimore, USA.
Aging is an etiologic factor in non-insulin-dependent diabetes mellitus.
While the effect of aging on insulin secretion has been described by
several classic studies, the characterization of the molecular basis of
beta-cell abnormalities is still under way. We recently demonstrated in
rats that aging is associated not only with a reduction in insulin
secretion but also with diminished levels of intracellular insulin content
and the mRNA for insulin. In this study, we investigated whether the
molecular abnormalities previously described in the rat beta cell were also
present in the mouse (C57BL/6J). Total cellular RNA was isolated from
individual pancreata of 3-, 9-, and 30-month-old mice (n = 6 per age
group). Samples were subjected to slot-blot analysis by using homologous
probes for insulin, glucagon, somatostatin, glucose transporter-2 (glut-2),
glucokinase, elastase-I, and beta-actin. We observed a progressive
age-dependent decrease in insulin mRNA levels: insulin mRNA levels
decreased by 40% with age (p = .007). This paralleled decreases in glut-2
(p = .001) mRNA levels, but it was in contrast with glucokinase mRNA levels
which increased markedly (p = .0003). Somatostatin mRNA levels were
unchanged, glucagon mRNA levels decreased modesty (p = .01), and mRNA
levels for elastase-I and beta-actin increased with age (p = .0001 for
either one). In summary, it appears that in the mouse a progressive decline
in the activity of the endocrine pancreas occurs with aging. This
phenomenon seems to affect only the beta cells and not the alpha or delta
cells of the islet of Langerhans or the exocrine pancreas. This progressive
decline may represent the biological features of the age-dependent risk for
the development of diabetes.
