Diabetes, fatty acid synthesis increase

Following the administration of insulin to diabetic rats, fatty acid synthesis increases [90,100,102-104] as would be predicted, increases are observed in the citrate cleavage enzyme, fatty acid synthetase, and... 

D. Decreased insulin levels cause fatty acid synthesis to decrease and glucagon levels to increase. Adipose triacylglycerols are degraded. Fatty acids are converted to ketone bodies in liver a ketoacidosis can occur. There is increased decarboxylation of acetoacetate to form acetone, which causes the odor associated with diabetic ketoacidosis. 

Gellhorn and Benjamin (1966) have demonstrated that oxidative desaturation of saturated fatty acids becomes depressed in the diabetic state and that this enzymatic impairment is reversed by insulin. Since insulin can also reverse the diabetic depressed llpogenlc activity, it is fair to assume that the insulin-Induced rise in hepatic desaturase activity could be mediated by the increase in de novo fatty acid synthesis. Mercurl et al. (1974) demonstrated that dietary fructose or glycerol was able to partially restore the A9 desaturase activity depressed by the diabetic state. Since utilization of these carbohydrates by the liver is not insulin dependent (Takeda et al , 1967 and Howard and Lowenstein, 1967) and the fatty acid synthetase activity is increased by a fructose or glycerol supplemented diet (Volpe and Vagelos, 1974 and Bruckdorfer et al., 1972), further research in this area may increase our understanding of these metabolic relationships. 

The increased degradation of fat that occurs in insulin deficiency also has serious effects. Some of the fatty acids that accumulate in large quantities are taken up by the liver and used for lipoprotein synthesis (hyperlipidemia), and the rest are broken down into acetyl CoA. As the tricarboxylic acid cycle is not capable of taking up such large quantities of acetyl CoA, the excess is used to form ketone bodies (acetoacetate and p-hydroxy-butyrate see p. 312). As H"" ions are released in this process, diabetics not receiving adequate treatment can suffer severe metabolic acidosis (diabetic coma). The acetone that is also formed gives these patients breath a characteristic odor. In addition, large amounts of ketone body anions appear in the urine (ketonuria). 

In a placebo-controlled study in six patients with type 2 diabetes mellitus thalidomide 150 mg/day for 3 weeks reduced insulin-stimulated glucose uptake by 31% and glycogen synthesis by 48% (1115). However, it had no effect on rates of glycolysis, carbohydrate oxidation, non-oxidative glycolysis, lipolysis, free fatty acid oxidation, or re-esterification. The authors concluded that thalidomide increases insulin resistance in obese patients with type 2 diabetes. 

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