Relative importance of extracellular and intracellular Ca2+ for acetylcholine stimulation of insulin release in mouse islets. 1989

M P Hermans, and J C Henquin
Unit of Diabetology and Nutrition, University of Louvain School of Medicine, Brussels, Belgium.

Mouse islets were used to study whether mobilization of intracellular Ca2+ is sufficient to account for acetylcholine (ACh) amplification of glucose-induced insulin release. In the presence of 15 mM glucose, the acceleration of 45Ca efflux and insulin release by 1-100 microM ACh increased with the concentration of extracellular Ca2+ (0.25-2.5 mM). Low concentrations of the Ca2+-channel blockers D 600 (1 microM) or nifedipine (0.1 microM) partially inhibited glucose-induced insulin release and its amplification by ACh. At higher concentrations, D 600 (25 microM) or nifedipine (2 microM) practically abolished the ionic and secretory effects of 1 microM ACh. However, 100 microM ACh still caused a fast, large, but transient acceleration of 45Ca efflux, accompanied by a small, short-lived release of insulin. Similar results were obtained in a Ca2+-free medium, indicating that this peak of 45Ca efflux reflects Ca2+ mobilization. Addition of nifedipine or omission of Ca2+ during ACh stimulation rapidly and strongly inhibited 45Ca efflux and insulin release. Both glucose and ACh-induced 45Ca uptake were inhibited by D 600. Only high concentrations of ACh (100 microM) mobilize enough cellular Ca2+ to trigger a small and transient insulin release when Ca2+ influx is prevented or impossible. A continuous influx of Ca2+ is necessary for low ACh concentrations to increase release and for high concentrations to have a sustained effect. The amplification of release by the neurotransmitter results from a slight enhancement of Ca2+ influx associated with a marked increase in the effectiveness of incoming Ca2+ on the releasing machinery.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007515 Islets of Langerhans Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN. Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009543 Nifedipine A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. Adalat,BAY-a-1040,Bay-1040,Cordipin,Cordipine,Corinfar,Fenigidin,Korinfar,Nifangin,Nifedipine Monohydrochloride,Nifedipine-GTIS,Procardia,Procardia XL,Vascard,BAY a 1040,BAYa1040,Bay 1040,Bay1040,Monohydrochloride, Nifedipine,Nifedipine GTIS
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D005260 Female Females
D005711 Gallopamil Coronary vasodilator that is an analog of iproveratril (VERAPAMIL) with one more methoxy group on the benzene ring. Methoxyverapamil,D-600,D600,Elgiprona,Gallobeta,Gallopamil Hydrochloride,Prebet,Procorum,gallopamil von ct,D 600,Hydrochloride, Gallopamil
D000078790 Insulin Secretion Production and release of insulin from PANCREATIC BETA CELLS that primarily occurs in response to elevated BLOOD GLUCOSE levels. Secretion, Insulin
D000109 Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. 2-(Acetyloxy)-N,N,N-trimethylethanaminium,Acetilcolina Cusi,Acetylcholine Bromide,Acetylcholine Chloride,Acetylcholine Fluoride,Acetylcholine Hydroxide,Acetylcholine Iodide,Acetylcholine L-Tartrate,Acetylcholine Perchlorate,Acetylcholine Picrate,Acetylcholine Picrate (1:1),Acetylcholine Sulfate (1:1),Bromoacetylcholine,Chloroacetylcholine,Miochol,Acetylcholine L Tartrate,Bromide, Acetylcholine,Cusi, Acetilcolina,Fluoride, Acetylcholine,Hydroxide, Acetylcholine,Iodide, Acetylcholine,L-Tartrate, Acetylcholine,Perchlorate, Acetylcholine

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