Increased glucose sensitivity of stimulus-secretion coupling in islets from Psammomys obesus after diet induction of diabetes

When fed a high-energy (HE) diet, diabetes-prone (DP) Psammomys obesus develop type 2 diabetes with altered glucose-stimulated insulin secretion (GSIS). β-Cell stimulus-secretion coupling was investigated in islets isolated from DP P. obesus fed a low-energy (LE) diet (DP-LE) and after 5 days on a HE diet (DP-HE). DP-LE islets cultured overnight in 5 mmol/l glucose displayed glucose dose-dependent increases in NAD(P)H, mitochondrial membrane potential, ATP/ (ATP + ADP) ratio, cytosolic calcium concentration ([[[Ca.sup.2+]].sub.c]), and insulin secretion. In comparison, DP-HE islets cultured overnight in 10 mmol/l glucose were 80% degranulated and displayed an increased sensitivity to glucose at the level of glucose metabolism, [[[Ca.sup.2+]].sub.c], and insulin secretion. These changes in DP-HE islets were only marginally reversed after culture in 5 mmol/l glucose and were not reproduced in DP-LE islets cultured overnight in 10 mmol/l glucose, except for the 75% degranulation. Diabetes-resistant P. obesus remain normoglycemic on HE diet. Their β-cell stimulus-secretion coupling was similar to that of DP-LE islets, irrespective of the type of diet. Thus, islets from diabetic P. obesus display an increased sensitivity to glucose at the level of glucose metabolism and a profound β-cell degranulation, both of which may affect their in vivo GSIS.
Stimulation of insulin secretion by glucose requires oxidative metabolism of the sugar in β-cells, with acceleration of ATP production and increase of the ATP/ADP ratio (1-4). The subsequent closure of [...]