Dynamics of O2 consumption in rat pancreatic islets.
The O2 consumption of rat pancreatic islets was determined by monitoring pO2 in the perifusate from groups of 200-300 islets. Basal respiration was maintained for up to 2 h. The insulin secretagogues, glucose and 4-methyl-2-oxopentanoate, provoked an immediate (< 5 s) increase in islet respiration which attained a new steady-state within 10-40 min. The respiratory changes were immediately reversible upon removal of the substrate and were paralleled by changes in insulin release and substrate oxidation. The concentration dependence of glucose-induced respiratory changes was sigmoidal with a threshold at 3 mmol/l. The concentration dependence with 4-methyl-2-oxopentanoate was characterised by a hyperbolic relationship. The weak insuln secretagogues 3-methyl-2-oxobutyrate and d,l-3-methyl-2-oxopentanoate, although stimulating islet respiration were not more effective than 4- methyl-2-oxopentanoate at non-insulinotropic concentrations. Rotenone, antimycin and oligomycin inhibited both basal O2 consumption and the ability of glucose and 4-methyl-2-oxopentanoate to increase islet respiration. 2,4-Dinitrophenol increased islet O2 consumption. The omission of Ca2+ and Mg2+ from the perifusing media, or the addition of the ionophore A23187, had little effect on respiration. The omission of K+ inhibited glucose-induced changes but had a lesser effect in the absence of substrate or in the presence of 4-methyl-2-oxopentanoate. The omission of HCO3-reduced both basal and secretagogue-induced changes in islet respiration. It is concluded that mitochondrial O2 consumption linked to oxidative phosphorylation is a major component in the respiratory response, and that some energy consuming process in the islets depends on the availability of HCO3-. Mitochondrial reactions may generate a signal initiating the secretory process.
D000090:Acetoacetates / Q000378:metabolism; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002245:Carbon Dioxide / Q000378:metabolism; D004573:Electrolytes / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D012402:Rotenone / Q000494:pharmacology
D000090:Acetoacetates; D000596:Amino Acids; D000900:Anti-Bacterial Agents; D004573:Electrolytes; D007328:Insulin; D007651:Keto Acids; D012402:Rotenone; D002245:Carbon Dioxide; C013082:alpha-ketoisocaproic acid; D006861:Hydrogen Peroxide; D005947:Glucose