(1) Acute insulin deficiency was produced in rats by the intravenous administration of potent anti-insulin guinea pig serum. Plasma glucose and nonesterified fatty acid (NEFA) levels rapidly increased to an excess of 350 mg. per cent and 1,200 μEq/L. respectively, and were kept elevated by repeated injections of anti-insulin serum.

(2) Hepatic fatty acid synthesis was determined by measuring the incorporation of acetate-1-C-14, acetyl-1-C-14 CoA, and malonyl-1,3-C-14 CoA into fatty acid by cell-free liver homogenates. Within 90 min. after the induction of acute insulin deficiency, acetate and acetyl CoA incorporation were markedly decreased, but malonyl CoA conversion to fatty acids was unaffected, indicating a block in lipogenesis at the acetyl CoA carboxylase step.

(3) The acute inhibition of carboxylase appeared to be a feedback mechanism since significant increases in hepatic tissue NEFA were observed when fatty acid synthesis decreased, and similar patterns of inhibition could be reproduced in normal rat liver homogenates by addition of either palmitate or palmityl CoA.

(4) Hepatic protein synthesis, measured by the incorporation of lysine-U-C-14 did not become impaired until three hours after the induction of acute insulin deficiency. The delayed onset of inhibition and the failure to observe impairment of protein synthesis following the in vitro addition of palmitate, suggest that the factor(s) responsible for impaired hepatic protein synthesis following acute insulin deprivation differ from those causing impaired lipogenesis under similar conditions.

(5) In contrast to previous reports using chronically insulin deprived animals (alloxan diabetes), the protein synthesizing activity of both soluble and microsomal fractions was impaired following acute insulin deprivation.

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