Glucose transport and metabolism in rat renal proximal tubules: multicomponent effects of insulin.
Glucose transport and metabolism, and the effect of insulin thereon, was studied using suspensions of rat renal tubules enriched in the proximal component. [U-14C]Glucose oxidation is a saturable process (Km 3.1 +/- 0.2 mM; Vmax 14 +/- 0.2 mumole 14CO2 formed/g tissue protein per h). Glucose oxidation and [14C]lactate formation from glucose are inhibited in part by phlorizin and phloretin: the data suggest that the rate-limiting entry of glucose into the cell metabolic pool occurs by both the Na-glucose cotransport system (at the brush border) and the equilibrating, phloretin-sensitive system (at the basal-lateral membrane). Raising external glucose from 5 to 30 mM markedly increases aerobic and anaerobic lactate formation. Gluconeogenesis from lactate is not affected by variations of glucose concentrations. 24 h after streptozotocin administration, aerobic lactate formation is enhanced, as is the uptake of methyl alpha-D-glucoside by the tubules, while anaerobic glycolysis is depressed. Streptozotocin treatment (ST) increases both the Km and Vmax of glucose oxidation; gluconeogenesis and lactate oxidation are not affected. The effect of streptozotocin treatment on lactate formation are abolished by 1 mU/ml insulin. Streptozotocin treatment increases tissue hexokinase activity, decreases glucose-6-phosphatase, but has no significant effect on fructose-1,6-diphosphatase; phosphoenolpyruvate carboxykinase and pyruvate dehydrogenase. The data demonstrate fast streptozotocin-induced changes in cellular enzymes of carbohydrate metabolism. The enhancing effect of streptozotocin on methyl alpha-glucoside uptake is transient: 8 days after administration of the agent, no significant difference from controls is found. It is concluded that under the given experimental conditions insulin enhances the equilibrating glucose entry by the phloretin-sensitive pathway at the basal-lateral membrane, and transiently inhibits the Na-glucose cotransport system.
D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D010084:Oxidation-Reduction; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology
D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D013311:Streptozocin; D000496:Alloxan; D012964:Sodium; D010695:Phlorhizin; D005947:Glucose