In-vitro and In-vivo Responsiveness of Muscle and Adipose Tissue to Insulin in Rats Rendered Obese by a High-fat Diet

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Abstract
The influence of insulin on [6-14C] glucose metabolism was assessed in vitro and in vivo in epididymal adipose tissue and diaphragm of rats fed either a low-fat (9 per cent fat cal.) or a high-fat diet (72 per cent fat cal.) In vitro, diaphragm of fat-fed rats showed a lower glucose uptake than that of rats fed the low-fat diet, but had identical glycogen labeling and lactic acid production and a strongly reduced 14CO2 production. Responsiveness of these pathways to insulin was unaltered by the fat content of the diet. The adipose tissue of fat-fed rats versus that of rats fed the low-fat diet showed: a higher lactic acid production and more efficient glycerogenesis and glycogenesis, all of these pathways being responsive to insulin; a lower glucose uptake and a strongly depressed fatty acid labeling, these two pathways being unresponsive to insulin. In-vivo labeling of glycogen in diaphragm in both basal and insulin-stimulated conditions was identical in the two groups of rats. In adipose tissue the amount of 14C sequestered in the ghyceride-glycerol moiety was the same in the two groups in basal and insulin-stimulated conditions, whereas the labeling of the fatty acid moiety and its increment with insulin were reduced by more than 99 per cent by the high-fat diet. These results show that alterations in fat content of the diet lead to differences in response to insulin that are pathway- and organ-specific.