Principles of Biochemistry, Volume 3 - A. Lehninger 1985

Selected Aspects of Human Biochemistry
Hormones
Insulin affects many metabolic processes

Chapter 24 described A number of other metabolic alterations associated with Insulin deficiency. For example, in human patients with diabetes or in animals with experimental diabetes induced by pancreatectomy or by the destruction of islet tissue via alloxan administration (Fig. 25-18), The ability to synthesize Fatty acids and Lipids from glucose is lost. At the same time, The rate of Fatty acid oxidation exceeds normal levels, leading to an excess production of Ketone Bodies that accumulate in Tissues, Blood, and urine—a condition known as Ketosis. In animals with experimental diabetes, the rate of Amino Acid Transport from the blood into peripheral tissue Cells is also reduced, thereby slowing down Protein Synthesis. Instead, Amino Acids undergo deamination in the Liver, and their carbon skeletons are converted via Gluconeogenesis (Section 20.1) into glucose, which is released into the blood. These Metabolic Disorders (Table 25-6) are reversed upon the administration of insulin.

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Fig. 25-18. Structure of alloxan, a pyrimidine derivative that induces experimental diabetes in animals by destroying islet cells.

Table 25-6. Metabolic shifts in insulin deficiency (Diabetes Mellitus)

The entire complex of metabolic shifts caused by insulin deficiency can be viewed as evidence that, in diabetes, the body acts as if it were trying to convert all available nutrients into blood glucose. The tissues are in urgent need of glucose, and the liver works overtime to synthesize it; however, this only results in the greater part of the glucose being lost in the urine. According to this perspective on the metabolic defect in diabetes, the patient's tissues are unable to take up glucose from the blood at normal levels (~4.5 mM); an effectively higher glucose concentration is required for proper uptake. Yet when the blood glucose concentration rises above 10 mM—the renal threshold—the excess glucose is excreted in the urine, resulting in massive losses of glucose from the body.

Other severe metabolic abnormalities in diabetes mellitus do not respond to insulin therapy. Specifically, diabetes impairs The biosynthesis of the basement membrane in blood capillaries, leading to vascular damage in The Heart, Kidneys, extremities, and retina. Consequently, advanced stages of diabetes lead to complications such as blindness and renal failure. Apparently, a single daily injection of insulin fails to replicate the physiological fluctuations in blood insulin levels that occur on an hourly or even minutely basis in healthy islet tissue in response to shifting blood glucose concentrations. This underscores the need to develop automated devices for delivering insulin into the bloodstream at a rate proportional to blood glucose concentrations. Such devices would more accurately mimic the secretory function of normal islet tissue in vivo.