Insulin release in aging: the role of glyceraldehyde

Abstract. Glucose-stimulated insulin release is decreased from pancreatic islets of older rats. The mechanism for this and its relationship to the hyperglycaemia of aging remain to be fully elucidated. We have recently shown that adenylate cyclase activity is reduced in islets from older rats and this might, in part, account for the decreased insulin release. It has been shown, however, that islet glucose oxidation is also reduced in aging. In an attempt to gain further insight into the biochemistry of this age-related decrease in insulin release, we investigated D-glyceraldehyde-stimulated insulin secretion. Simultaneous experiments were performed on islets from 2 and 13 month old rats to determine insulin release in response to 2.8 mM or 16.7 mm d-glucose or 2.8 mm d-glucose + 2.5, 5.0, 7.5, 10.0 or 14.4 mm d-glyceraldehyde. Islets were incubated for 30 min at 37°C in a metabolic shaker bath and the media were then assayed for insulin by conventional radioimmunoassay. Insulin secretion in response to 2.8 mm d-glucose was similar in the two groups of islets (9.8 ± 0.9 pg insulin islet−1min−1 from old vs 8.9 ± 1.0 from the young control rats, P < 0.2). Insulin release was diminished by 32% from islets of older rats in the presence of 16.7 mm d-glucose compared with islets from young control rats (84.0 ± 5.6 pg insulin islet−1min−1 from older animals vs 123.5 ± 10.7 from controls, P < 0.001). In the presence of 2.8 mm d-glucose + all concentrations of d-glyceraldehyde used, insulin release was similar from islets of older and young rats. From these results, it appears that the diminished insulin release from islets of older rats involves not only changes in the adenylate cyclase system, but also may involve changes in glucose metabolism at a rate-limiting step in stimulus-secretion coupling before the metabolism of the trioses.