Insulin release in aging: dynamic response of isolated islets of Langerhans of the rat to D-glucose and D-glyceraldehyde.

Glucose-stimulated insulin release is diminished in islets of Langerhans from older rats compared to that in islets from young controls. The causes of this age-related decrease in hormone release and its relationship to the hyperglycemia seen in aging populations have not been fully elucidated. In attempts to define this secretory defect, we demonstrated in static studies that the insulin secretion to D-glyceraldehyde is not diminished in aging. To gain further insight into the effects of D-glyceraldehyde vs. D-glucose in aging and to understand the dynamics of insulin release from islets of older rats, dynamic insulin release from isolated islets of 2.5- and 13-month-old rats was studied by the technique of perifusion to 2.8 mM and 16.7 mM D-glucose or 2.8 mM D-glucose with 5, 10, or 14 mM D-glyceraldehyde. Insulin secretion at nonstimulatory glucose concentrations (2.8 mM) was similar in the two groups of islets. Insulin release was reduced by 36% from islets of older rats incubated in the presence of 16.7 mM D-glucose, and the first phase of insulin release was largely blunted compared with that in islets from young controls. In the presence of 5.0, 10.0, or 14.0 mM D-glyceraldehyde (plus 2.8 mM D-glucose), total insulin secretion was similar from islets of older and young rats, and normal biphasic release was restored to islets from older rats. Response to the secretagogues was delayed by 1 min in studies on islets from older rats. These findings demonstrate that while the aging process leads to a profound defect in glucose-stimulated insulin release from the pancreatic beta-cell, this defect is not present with every secretagogue, since the normal secretory response is restored in the presence of D-glyceraldehyde. The differences in the insulin secretory responses to D-glucose and D-glyceraldehyde in islets from older rats support the hypothesis that the major rate-limiting step in stimulus-secretion coupling in aging is before the metabolism of the trioses.