Effects of Age and of Fasting on the Responsiveness of the Insulin-Secreting Mechanism of the Islets of Langerhans to Glucose

Abstract

Insulin responsiveness to glucose of isolated islets of Langerhans was studied in 'younger' and 'older' rats after feeding and fasting for various lengths of time. In 'younger' rats, after prolonged fasting (168 h) the threshold for glucose-stimulated insulin secretion was increased. This was not evident in islets from 'younger' rats fasted for 48 or 89 h. Reductions in increments of insulin secretion with increments in glucose, in the maximum insulin secreted and in the total extractable insulin of the islets were apparent after fasting for 48, 89 and 168 h as compared with islets from fed rats. In 'older' rats, prolonged fasting caused an increase in the threshold for glucose-stimulated insulin secretion, reduced incremental insulin secretion, reduced maximum insulin secretion and reduced total extractable insulin. However, the responses of islets from fed 'older' rats were similar to those of fasted (168 h) 'younger' rats. The threshold levels were similar, and there were no significant differences between increments in insulin secretion, maximum insulin secretion and insulin content of the islets. These experiments show that the responsiveness of islets of Langerhans in rats can be altered by age and fasting.

Secretion of Insulin During Aging

“…However, the low responsiveness is also in agreement with the results of others who examined dispersed islet cells 54–58 . The apparent absence of diminished insulin responsiveness to glucose by isolated islet beta cells as donor rats age 53 also suggests that feedback inhibition of glucose‐stimulated insulin secretion by insulin from isolated islets of aged rats 29 either requires the integrity of an intact islet architecture or is susceptible to damage by the methodology utilized for dispersion of islet cells.…”

“…2) Age differences in glucose‐stimulated insulin response are minimized unnecessarily by the selection of 10 and 14 months as old Wistar rats, and 18 months as old Sprague‐Dawley rats 26 . 3) The authors fail to acknowledge previous literature that documents the impact of aging on glucose‐stimulated insulin release by rat islets, 1,13,27–29 as well as the need for methodological precautions in this type of research 30 …”

Role of the adenylate cyclase system in altered insulin release from islets of Langerhans of aging rats

“…Clinical human studies of insulin secretion in aging man and in vivo studies in aging rats have shown increased, unchanged or decreased glucosestimulated insulin release with increasing age (Andres et al 1970;Berdanier et al 1971;Nolan et al 1973;DudI & Ensinck 1977;Soerjodibroto et al 1979), and it is unclear whether population samp¬ ling, differences in adiposity or nutritional state play a role in explaining these differences (Andres & Tobin 1977;Gregerman & Bierman 1974). In order to study directly insulin secretion in aging, isolated islets of Langerhans from older rats have been used as a model system to explore the age related changes in B-cell function (Coddling et al 1975;Gold et al 1976;Kitahara & Adelman 1979;Reaven et al 1979). …”

“…Cli¬ nical human studies and in vivo animal studies have not been in agreement as to whether insulin release is altered to glucose stimulation in aging (Andres et al 1970;Berdanier et al 1971;Nolan et al 1973;Dudl & Ensinck 1977;Soerjodibroto et al 1979;Davidson 1979) and the resulting uncertainty is still not resolved. Recent investigations using isolated islets of Langerhans from aging rats have shown there is diminished glucose-stimulated insulin re¬ lease when compared with islets from younger animals (Coddling et al 1975;Gold et al 1976;Kitahara & Adelman 1979;Reaven et al 1979), but causes for the observed aging-induced secretory defect have not been elucidated.…”