Cytosolic ratios of free INADPHI / INADP + I and INADHI / INAD + I in mouse pancreatic islets , and nutrient - induced insulin secretion

When the extracellular concentration of glucose was raised from 3 mm to 7 mm (the concentration interval in which fl-cell depolarization and the major decrease in K+ permeability occur), the cytosolic free [NADPH]/ [NADP+] ratio in mouse pancreatic islets increased by 29.5% . When glucose was increased to 20 mm, a 117% increase was observed. Glucose had no effect on the cytosolic free [NADH]/[NAD+] ratio. Neither the cytosolic free [NADPH]/[NADP+] ratio nor the corresponding [NADH]/[NAD+] ratio was affected when the islets were incubated with 20 mM-fructose or with 3 mM-glucose+ 20 mM-fructose, although the last-mentioned condition stimulated insulin release. The insulin secretagogue leucine (10 mM) stimulated insulin secretion, but lowered the cytosolic free [NADPH]/[NADP+] ratio; 10 mM-leucine+10 mM-glutamine stimulated insulin release and significantly enhanced both the [NADPH]/[NADP+] ratio and the [NADH]/[NAD+] ratio. It is concluded that the cytosolic free [NADPH]/[NADP+] ratio may be involved in coupling fl-cell glucose metabolism to fl-cell depolarization and ensuing insulin secretion, but it may not be the sole or major coupling factor in nutrient-induced stimulation of insulin secretion.