Evidence for Age-Related Changes in Pyridine Nucleotide Content of Isolated Rat Islets

Summary

The purpose of this study was to document the effect of age on α-glycerophosphate activity and pyridine nucleotide concentration in pancreatic islets isolated from rats. In order to do this, islets were isolated from pancreases of 2 and 12 month-old rats, and measurements made of α-glycerophosphate activity and of NAD⁺ and NADH, determinations were made following incubation at both basal (5.6 mM) and elevated glucose concentrations (28 mM). The results indicated that islet α-glycerophosphate dehydrogenase activity was decreased (P < 0.001) by approximately 50% in the older rats. This was associated with an increase in mean (±SEM) basal NADH content (pmol/μg DNA) in 12 month-old (4.48±0.31) as compared to 2 month-old rats (2.73±0.49). Although mean (±SEM) basal NAD⁺ levels (pmol/μg DNA) were the same in 2 and 12 month-old rats (29.4±2.5 and 30.8±2.8, respectively), NAD⁺ content following incubation at elevated levels of glucose declined (absolutely and relatively) to a significantly greater degree in the younger rats. The incremental rise in islet NADH concentration following incubation at the elevated glucose concentration was similar in the two groups, but the relative increase was only approximately half as great in islets from 12 month-old rats. These data indicate that the age-related decline in the activity of α-glycerophosphate dehydrogenase, the enzyme regulating the glycerophosphate shuttle system in 12 month-old rats, is associated with alterations in islet pyridine nucleotide composition. A predictable consequence of these events would be a decrease in rate of glycolysis in islets of older rats, and this may help explain the age-related reduction in glucose-stimulated insulin secretion per beta cell that has previously been reported.

Key-Words

Beta Cell - Pancreatic Islets - α-Glycerophosphate Dehydrogenase Activity - Pyridine Nucleotides