-Triglycerides : Fatty Acids
FIGURE 7-32 Comparison for liver, muscle, and adipose tissue of the major metabolic effects that occur in the absence and presence of insulin. Thick solid arrows show the pathways that are favored in the presence of insulin, while thick broken arrows depict those that predominate when the action of the hormone is insufficient. For an explanation, see the text. [Modified with permission from Gilman, A. G., Goodman, L. S., and Gilman, A. (1980). "The Pharmacological Basis of Therapeutics," 6th ed. Macmillan, New York.]
and finally blood-delivered free fatty acids derived from adipose and hepatic stores.
Adipose tissue is one of the principal target organs for insulin action. The extensive amount of triglycerides stored in adipocytes serves as an important fuel source under conditions of dietary caloric restriction or prolonged exercise. The mobilized free fatty acids are systematically delivered to a number of key organs (heart and kidney), which can directly utilize them as a substrate for oxidative metabolism. If the free fatty acids were taken up by the liver, they could be esteri-fied into triglycerides or phospholipids, oxidized to CO2, or more likely converted into ketones, particularly /3-hydroxybutyrate and acetoacetate. These ketones in turn can also serve as fuels for most extrahepatic tis
sues, particularly the brain, under conditions of very low blood glucose levels.
Insulin can suppress ketogenesis via two general mechanisms: (i) In the adipocyte, insulin inhibits lipol-ysis, which generates free fatty acids, (ii) In the liver, insulin also blocks or reduces the extent of liver oxidation and enhances the storage of the free fatty acids as triglycerides.
The rate-limiting step in the biosynthesis of triglycerides by both the liver and adipose tissue is the availability of glycerol phosphate. This three carbon sugar is not transported through the blood; hence, it must be generated in situ in the cell where triglyceride synthesis is occurring. This in turn implies that there should be adequate supplies of substrates to the glycolytic pathway to ensure the availability of the glycerol phosphate in sufficient amounts.
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