Insulin release : the fuel concept.
Insulin release evoked by nutrient secretagogues invariably coincides with an increase in the catabolism of exogenous and/or endogenous nutrients in pancreatic islet cells, resulting in an increased generation rate of reducing equivalents and ATP, and an increase in O2 consumption. This situation was documented in response to a number of carbohydrates, including the anomers of D-glucose and D-mannose, various 2-keto acids, including pyruvate and its poorly oxidized phenylated analog 3-phenylpyruvate, and selected amino acids, including the nonmetabolized analog of L-leucine 2-aminobicyclo[2, 2, 1]heptane-2-carboxylic acid. These convergent observations indicate that the B-cell should be considered as a fuel-sensor organ. Further progress in this field requires both the identification of those circulating nutrients used by the B-cell whether in the resting or stimulated state, and a better understanding of the coupling between the generation of second messengers (H+, NAD(P)H, ATP) and more distal events in the secretory sequence, such as the remodelling of ionic fluxes across the plasma membrane and within the pancreatic B-cell.
D000596:Amino Acids / Q000494:pharmacology; D002208:Caproates / Q000494:pharmacology; D004734:Energy Metabolism; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006019:Glycolysis; D006601:Hexoses / Q000494:pharmacology; D006801:Humans; 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; D008954:Models, Biological; D009646:Norleucine / Q000494:pharmacology; D010667:Phenylpyruvic Acids / Q000494:pharmacology; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D002208:Caproates; D005958:Glucosephosphates; D006601:Hexoses; D007328:Insulin; D007651:Keto Acids; D010667:Phenylpyruvic Acids; D011773:Pyruvates; C001916:alpha-ketocaproic acid; D019298:Glucose-6-Phosphate; C013082:alpha-ketoisocaproic acid; D009646:Norleucine; D019289:Pyruvic Acid; D007930:Leucine; C031606:phenylpyruvic acid