Nutrient secretagogues induce bimodal early changes in cytoplasmic calcium of insulin-releasing ob/ob mouse beta-cells.
The cytoplasmic calcium concentration (Ca2+i) was measured in suspensions of fura-2 loaded mouse pancreatic beta-cells by continuously recording the 340/380 nm fluorescence excitation ratio. When the glucose concentration was raised from 3 to 20 mM, there was an initial lowering of Ca2+i followed by a sustained increase. Whereas the reduction in Ca2+i was related to the extracellular glucose concentration in a hyperbolic manner, the increasing component exhibited a sigmoidal dose-response relationship. Both effects became maximal at 15-20 mM of the sugar. Qualitatively similar bimodal Ca2+i responses were obtained with 30 mM mannose, 2 mM alpha-ketoisocaproic acid, 10 mM leucine, and 10 mM metabolism-stimulating leucine analogue beta-2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid. Fructose (30 mM) had virtually no effect on Ca2+i in the presence of extracellular Ca2+, and 10 mM arginine induced only a rise. The results indicate that nutrient secretagogues stimulate both the entry of Ca2+ into the beta-cells and its elimination from the cytoplasm by processes like organelle sequestration and outward transport. Consequently, the Ca2+i level determining insulin secretion results from the balance between two opposing actions.
D000596:Amino Acids / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology; D007930:Leucine / Q000494:pharmacology; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism*
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D007328:Insulin; D007651:Keto Acids; D005973:Glutamine; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; C013082:alpha-ketoisocaproic acid; D001120:Arginine; D007930:Leucine; D005947:Glucose; D002118:Calcium