Insulin release and metabolism of calcium, adenine and adenosine 3',5'-cyclic monophosphate.

Abstract

SynopsisIn order to assess further the mechanisms involved in insulin release, we prelabeled rat pancreatic islets of Langerhans by incubating either 45Ca or [2-3H]adenine. When prelabeled islets were perfused with a glucose-free medium (the experiment with and a medium containing2.8mM glucose (the experiment with [2-3H] adenine) respectively, a constant rate of efflux of the radioactivity was established by30min in each case. D-Glucose at16.7mM concentration elicited a rapid efflux of "Ca and No rapid efflux of45Ca was observed under a slow-rise glucose stimulation until the gradient level of the glucose concentration was raised to6.7mM.Analysis of distribution of the radioactive adenine derivatives after incubation showed that the adenosine fraction had the highest radioactivity in the medium followed by the ATP, adenine and cAMP fraction in that order, and the ATP fraction had the highest radioactivity in the islet.

Glucose increases the synthesis of lipoxygenase-mediated metabolites of arachidonic acid in intact rat islets.

“…Further, at submaximal concentrations, the a anomer of D-Glc was considerably more potent than the f3 anomer in promoting 12-HETE formation, in parallel with the anomeric preference with regard to phosphorylation by glucokinase (20), glycolytic metabolism, and insulin secretion (21). The anomeric preference with regard to all four parameters occupies a narrow "window," with the difference being most obvious near the Glc threshold with the P anomer actually becoming slightly more potent at supramaximal hexose concentrations (22).…”

Control, modulation, and regulation of cell calcium

“…Meer 1974;Dziak and Stern 1975Deshmukh et al 1977Wattington et al 1968 BorIe 1969, c Yamaguchi et al 1975Yamaguchi 1979Harrell et al 1973Binderman et al 1974;Eilam et al 1980 Glucose Pancreas Carafoli and Crovetti 1973 ;Carafoli 1975 Rodan andRodan 1976;Gerrard et al 1977Rasmussen et al 1975Sehrier et al 1975 Wollheim et al 1978;Gylfe et al 1978;Tsumura et al 1979;Hersdmetz et al 1979Hersdmetz et al , 1980Hersehnelz and Mataisse 1980 13.1 Cyclic AMP Most peptide hormones bind to specific receptors on the membrane of their target cells, stimulate the enzyme adenylate cyclase, and increase the intracellular concentration of cyclic AMP. Several other cyclic nucleotides such as cyclic GMP are also affected and there may be complex interactions among cyclic AMP, cyclic GMP, and calcium.…”

Dynamics of insulin and cyclic adenosine 3',5'-monophosphate release from the perifused rat islets of langerhans under a slow-rise stimulation with D-glucose and its anomers.

“…From the evidence available at the present time, it seems reasonable to assume that the effect of cAMP accumulated in rat islets of Langerhans may be mediated by the activation of a cAMP-dependent protein phosphokinase followed by phosphorylation of certain proteins which could be directly related to insulin mechanisms (Montague and Howell, 1972;Tsumura et al, 1979).…”