title: Slow [Ca2+]i oscillations induced by ketoisocaproate in single mouse pancreatic islets.
abstract: 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.
authors.affiliation: Department of Physiology, University of Alicante, School of Medicine, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Martin
authors.forename: J V
authors.initials: JV
authors.lastname: Sanchez-Andres
authors.forename: B
authors.initials: B
authors.lastname: Soria
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002208:Caproates / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D009991:Oscillometry; D013997:Time Factors
chemical_list: D002208:Caproates; D007328:Insulin; D007651:Keto Acids; D003994:Bucladesine; C013082:alpha-ketoisocaproic acid; D005934:Glucagon; D002118:Calcium