To determine if insulin resistance of obese hyperglycemic ob/ob mice might be due to an initial postreceptor defect, the effects of insulin and procaine HCI (0.1 mM) on glucose and fructose metabolism in their adipose tissue were studied. Procaine, unlike insulin, has been shown to exert its insulin-like effects on trypsinized adipocytes, suggesting an action independent of the insulin receptor. In the present study this agent, like insulin, stimulated glucose uptake, glycogenesis, pentose shunt activity, and lipid synthesis in tissue of lean littermates but not of ob/ob siblings. Prewashing has been shown to restore the sensitivity of their adipose tissue to insulin regarding antilipolysis and hexose metabolism, presumably by restoring available receptor number. In the present study, in contrast to the complete restoration of antilipolysis, prewashing only partially restored the effects of insulin (but not of procaine) on glycogenesis and lipid synthesis in tissue of ob/ob mice; no return of effects of either agent on glucose uptake or the pentose shunt occurred. Since hexose metabolism remained unresponsive to procaine and since prewashing restored only antilipolysis and a portion of the lipogenic effect of insulin (but not effects on glucose uptake or pentose shunt activity), these studies suggest an underlying irreversible defect in responsiveness of glucose uptake and the pentose shunt in adipose tissue of ob/ob mice independent of a deficiency of available insulin receptors. That portion of insulin resistance due to hyperinsulinemia and resulting receptor deficiency might be secondary to these underlying inherent defects.
Effects of Insulin and Procaine Hydrochloride on Adipose Tissue Hexose Metabolism in ob/ob Mice: Evidence of a Postreceptor Defect
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Herbert F Hope-Gill, Vinod Nanda, Ting-Po Kam; Effects of Insulin and Procaine Hydrochloride on Adipose Tissue Hexose Metabolism in ob/ob Mice: Evidence of a Postreceptor Defect. Diabetes 1 June 1979; 28 (6): 537–543. https://doi.org/10.2337/diab.28.6.537
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