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Reciprocal Variations in Insulin-Stimulated Glucose Uptake and Pancreatic Insulin Secretion in Women With Normal Glucose Tolerance

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Abstract

Objective

Maintenance of normal glucose tolerance is achieved in subjects with a wide range of insulin sensitivity. It follows, therefore, that the body must possess a sensor mechanism that assesses the body’s sensitivity to insulin and appropriately adjusts the secretion of insulin to maintain normal glucose homeostasis. We evaluated the relation between insulin action and insulin secretion.

Methods

Euglycemic hyperinsulinemic clamp (1 m U/kg · minute) and hyperglycemic clamp (+ 125 mg/dL) studies were performed in 32 non-obese women with normal oral glucose tolerance tests. The subjects were stratified into quartiles based upon their insulin-mediated rate of glucose uptake during the euglycemic insulin clamp.

Results

Total body glucose disposal varied threefold, ranging from 4.00 to HAS mg/kg · minute. A significant inverse relation (r = − 0.50, P < .01) was noted between the rate of total body insulin-mediated glucose disposal (insulin clamp) and the total plasma insulin response during the hyperglycemic clamp. Women in the lowest quartile of insulin sensitivity (mean glucose uptake 5.01 ± 0.20 mg/kg · minute) had the highest plasma insulin response during the hyperglycemic clamp (109 ± 20 μ U/mL). In contrast, women in the highest quartile of insulin sensitivity (glucose uptake 9.90 ± 0.38 mg/kg · minute) had the lowest plasma insulin response during the hyperglycemic clamp (55 ± 16 μ U/mL; P < .001 versus the lowest quartile).

Conclusions

These results demonstrate that among subjects with normal glucose tolerance, there exists a large variation in both insulin-mediated glucose uptake and pancreatic insulin secretion. Nonetheless, normal glucose tolerance is maintained because of a finely regulated balance, which couples the demand for insulin secretion by the pancreatic beta cells to the level of whole-body insulin sensitivity.

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Authors and Affiliations

  1. Departments of Obstetrics and Gynecology and Medicine, Vale University School of Medicine, New Haven, Connecticut, USA

    Michael P. Diamond MD, Kim Thornton MD, Meredith Connolly-Diamond RN, Robert S. Sherwin MD & Ralph A. DeFronzo MD

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  1. Michael P. Diamond MD
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  2. Kim Thornton MD
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  3. Meredith Connolly-Diamond RN
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  4. Robert S. Sherwin MD
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  5. Ralph A. DeFronzo MD
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Additional information

Supported in part by National Institutes of Health grants HD 28984 and AM 24092, a VA Merit Award, funds from the VA Medical Research Service, the GRECC, and General Clinical Research Center grant no. RR-125.

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Diamond, M.P., Thornton, K., Connolly-Diamond, M. et al. Reciprocal Variations in Insulin-Stimulated Glucose Uptake and Pancreatic Insulin Secretion in Women With Normal Glucose Tolerance. Reprod. Sci. 2, 708–715 (1995). https://doi.org/10.1016/1071-5576(95)00023-8

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