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

The effect of alpha-ketoisocaproate (KIC), the first catabolic metabol ite of the amino acid leucine, on [Ca2+](i), insulin release, and memb rane potential was measured in mouse pancreatic islets of Langerhans, Stimulatory concentrations of KIC (2.5-10 mmol/l) caused slow oscillat ions of [Ca2+](i) and cyclic variations of the membrane potential. Slo w [Ca2+](i) oscillations depended on extracellular calcium, Simultaneo us measurements of [Ca2+](i) and insulin release resolved pulsatile in sulin secretion that paralleled slow [Ca2+](i) oscillations. Whereas 1 1 mmol/l glucose induced a significant increase in cAMP, KIC was unabl e to modify it. Glucagon (10 nmol/l), which significantly increased cA MP in mouse islets, also increased the frequency of glucose-induced fa st [Ca2+](i) oscillations, However, neither glucagon (10 nmol/l) nor d ibutyryl cAMP (1 mmol/l) was able to change the slow oscillation patte rn into a fast pattern, imaging of Ca2+ showed that KIC-induced slow o scillations were synchronic throughout the whole islet. It is suggeste d that beta-cell electrical activity plays a role in the origin of slo w [Ca2+](i) oscillations.