Molecular Investigation of Age-Related Changes in Mouse Endocrine Pancreas

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Abstract
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 β-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 β 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 β-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 modestly (p = .01), and mRNA levels for elastase-I and β-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 β cells and not the α or δ 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.

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