SLOW [CA2+](I) OSCILLATIONS INDUCED BY KETOISOCAPROATE IN SINGLE-MOUSE PANCREATIC-ISLETS

The effect of alpha-ketoisocaproate (KIC), the first catabolic metabolite of the amino acid leucine, on [Ca2+](i), insulin release, and membrane potential was measured in mouse pancreatic islets of Langerhans, Stimulatory concentrations of KIC (2.5-10 mmol/l) caused slow oscillations of [Ca2+](i) and cyclic variations of the membrane potential. Slow [Ca2+](i) oscillations depended on extracellular calcium, Simultaneous measurements of [Ca2+](i) and insulin release resolved pulsatile insulin secretion that paralleled slow [Ca2+](i) oscillations. Whereas 11 mmol/l glucose induced a significant increase in cAMP, KIC was unable to modify it. Glucagon (10 nmol/l), which significantly increased cAMP in mouse islets, also increased the frequency of glucose-induced fast [Ca2+](i) oscillations, However, neither glucagon (10 nmol/l) nor dibutyryl cAMP (1 mmol/l) was able to change the slow oscillation pattern into a fast pattern, imaging of Ca2+ showed that KIC-induced slow oscillations were synchronic throughout the whole islet. It is suggested that beta-cell electrical activity plays a role in the origin of slow [Ca2+](i) oscillations.