The sensitivity and response to insulin in vitro of (a) the incorporation of U-C-14-glucose into glycogen in the isolated diaphragm muscle, and (b) the oxidation of l-C-14 glucose in the epididymal fat pad and in adipocytes, has been studied in obese hyperglycemic mice fed ad libitum, in obese mice fasted for twenty-four hours and in obese mice maintained on a restricted diet from weaning and in lean mice, at two to four months of age and at six to eight months of age.

In both age groups, there was a significant, although reduced, insulin effect in the muscle from obese mice but this was normal in the six to eight-month-old group of obese mice on a restricted diet.

The glucose oxidation in the epididymal fat pad of the obese mice fed ad libitum was very reduced in both age groups. Fasting the obese mice for twenty-four hours did not restore glucose oxidation to normal, but it was normal in fat pads from obese mice kept on a restricted diet. There was no insulin effect on the fat pad of obese mice in either age group even after a twenty-four-hour fast. The response and sensitivity of the tissue to insulin was partially restored in the obese mice on a restricted diet.

There were only small differences in sensitivity between adipocytes prepared from obese and lean epididymal fat pads. The maximum response to insulin in adipocytes from obese mice was usually lower than that in adipocytes from lean mice at glucose concentrations of 0.03 per cent but equal or higher at glucose concentrations of 0.2 per cent.

The clear responses to low concentrations of insulin of the isolated diaphragm muscle and adipocyte suspension from obese mice on a restricted diet and of the adipocytes from obese mice fed ad libitum, suggest that a decreased sensitivity to insulin at the cellular level is not the primary defect in the obese hyperglycemic syndrome.

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