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Diabetes Mellitus and the Metabolic Syndrome

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and (3) it inhibits gluconeogenesis and increases protein synthesis (Table 33-1). 2,3 Insulin acts to promote fat storage by increasing the transport of glucose into fat cells (Fig. 33-2). It also facilitates triglyceride synthesis from glucose in fat cells and inhibits the intracellular breakdown of stored triglycerides. Insulin also inhib- its protein breakdown and increases protein synthesis by increasing the active transport of amino acids into body cells, and it inhibits gluconeogenesis, or the build- ing of glucose from new sources, mainly amino acids. When sufficient glucose and insulin are present, protein breakdown is minimal because the body is able to use glucose and fatty acids as a fuel source. In children and adolescents, insulin is needed for normal growth and development. The active form of insulin is composed of two poly- peptide chains—an A chain and a B chain (Fig. 33-3). Active insulin is formed in the beta cells from a larger molecule called proinsulin. In converting proinsulin to insulin, enzymes in the beta cell cleave proinsulin at spe- cific sites to form two separate substances: active insulin and a biologically inactive C-peptide (connecting pep- tide) chain that joined the A and B chains before they were separated. Active insulin and the inactive C-peptide chain are packaged into secretory granules and released simultaneously from the beta cell. The C-peptide chains can be measured clinically, and this measurement can be used to study beta cell function (i.e., persons with

Pancreatic acini

Alpha cell

Beta cell

Delta cell

Islet of Langerhans

Red blood cells

FIGURE 33-1. Islet of Langerhans in the pancreas.

Insulin Although several hormones are known to increase blood glucose levels, insulin is the only hormone known to have a direct effect in lowering blood glucose levels. The actions of insulin are threefold: (1) it promotes glucose uptake by target cells and provides for glucose storage as glycogen, (2) it prevents fat and glycogen breakdown,

TABLE 33-1 Actions of Insulin and Glucagon on Glucose, Fat, and Protein Metabolism Insulin Glucagon

Glucose Glucose transport

Increases glucose transport into skeletal muscle and adipose tissue

Glycogen synthesis Gluconeogenesis

Increases glycogen synthesis Decreases gluconeogenesis

Promotes glycogen breakdown Increases gluconeogenesis

Fats Fatty acid and triglyceride synthesis Fat storage in adipose tissue

Promotes fatty acid and triglyceride synthesis by the liver Increases the transport of fatty acids into adipose cells Increases conversion of fatty acids to triglycerides by increasing the availability of α -glycerol phosphate through increased transport of glucose in adipose cells Maintains fat storage by inhibiting breakdown of stored triglycerides by adipose cell lipase

Activates adipose cell lipase, making increased amounts of fatty acids available to the body for use as energy Increases amino acid uptake by liver cells and their conversion to glucose by gluconeogenesis

Proteins Amino acid transport

Increases active transport of amino acids into cells

Protein synthesis

Increases protein synthesis by increasing transcription of messenger RNA and accelerating protein synthesis by ribosomal RNA Decreases protein breakdown by enhancing the use of glucose and fatty acids as fuel

Protein breakdown