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. 1976 Apr;57(4):842–851. doi: 10.1172/JCI108360

The effects of spontaneous obesity on insulin binding, glucose transport, and glucose oxidation of isolated rat adipocytes.

J M Olefsky
PMCID: PMC436727  PMID: 181402

Abstract

We have studied insulin, binding, glucose transport, and glucose oxidation, using large adipocytes isolated from older, fatter rats (greater than 12-mo-old, greater than 550 g), and smaller cells obtained from younger, leaner animals (4-5-wk-old, 120-160 g). At media glucose levels less than 5 mM, basal (absence of insulin) rates of glucose oxidation are comparable in both groups of cells. However, in the presence of insulin, the increase in glucose oxidation is much greater in the smaller cells. Maximally effective insulin levels could not overcome the defect in glucose oxidation by larger cells, and thus, even though studies of insulin binding demonstrated a 30-40% decrease in insulin receptors on the larger cells, it is probable that the defect in glucose oxidation is distal to the insulin receptor. Glucose transport was assessed by direct measurement of 2-deoxy glucose uptake. Basal levels of uptake were greater for the larger cells, whereas at maximally effective insulin concentrations, rates of 2-deoxy glucose uptake were the same for both groups of cells. Thus, in the presence of maximally effective levels of insulin, the apparent Km (2.3-2.7 mM) and Vmax values (2.6 and 2.7 nmol/10(5) cells per min) of 2-deoxy glucose uptake were comparable, indicating that the glucose transport system of the larger cells was intact. However, at submaximal levels of insulin, small adipocytes took up more 2-deoxy glucose than larger cells. These findings represent a rightward shift in the insulin dose-response curve in the cells from the older, fatter animals, and this is the predicted functional sequelae of the observed decrease in insulin receptors. Finally, when the amount of insulin bound was plotted as a function of 2-deoxy glucose uptake, no difference was seen between both groups of cells. This indicates that coupling between insulin receptor complexes and the glucose transport system is intact in large adipocytes, and is further evidence that a defect(s) in intracellular glucose metabolism is responsible for the decrease in glucose oxidation of adipocytes from older, fatter rats. In conclusion: (a) insulin-mediated glucose oxidation is markedly decreased in large adipocytes from older, fatter rats, and since this decrease cannot be corrected by maximally effective insulin levels, the defect is probably distal to the insulin receptor; (b) the glucose transport system is basically normal in large adipocytes; (c) insulin binding to receptors is decreased in large cells and the functional sequelae of this decrease in insulin binding i.e., a rightward shift in the insulin dose-response curve for 2-deoxy glucose uptake, was observed, and (d) since the decreased rates of insulin-mediated glucose oxidation can not be attributed to changes in insulin receptors or to changes in glucose transport, an intracellular defect in glucose metabolism is suggested.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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