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Metabolic effects of insulin
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PROINSULIN, INSULIN, AND C-PEPTIDE
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Insulin consists of two peptide chains linked by two disulfide bonds (Fig. 20.4). The α-chain contains 21 amino acidsView drug information and the β-chain 30 amino acidsView drug information. The molecular weight of insulin monomer is 5500 Da. The precursor of insulin within the β-cells of the islet of Langerhans is the single chain preproinsulin. During insulin synthesis a 24-amino-acid signal sequence is first cleaved from preproinsulin by a peptidase, yielding proinsulin.
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Proinsulin consists of the insulin sequence interspersed by a connecting peptide (C-peptide). At the final stage of insulin synthesis, proinsulin is split into insulin and C-peptide (Fig. 20.3), both of which are then released from the cell. C-peptide is released in an amount equimolar to insulin. This is exploited in the clinical laboratories to assess β-cell function in patients treated with exogenous (therapeutically injected) insulin. In these patients, endogenous insulin cannot be measured directly, because the exogenous insulin would interfere in the assay. In such circumstances, C-peptide measurement provides an assessment of β-cell function.
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In the liver, insulin stimulates both glycolysis and glycogen synthesis. At the same time, it suppresses lipolysis and promotes the synthesis of the long-chain fatty acids (lipogenesis). Lipids are then packaged into very-low-density lipoproteins (VLDL), which are secreted into the blood. In the peripheral tissues, insulin induces lipoprotein lipase, an enzyme that liberates triacylglycerol from either hepatic VLDL or dietary chylomicrons by hydrolyzing them into glycerol and fatty acids (see Chapter 17). Insulin also stimulates triglyceride synthesis from glycerol-3-phosphate and fatty acids in the adipose tissue. In muscle, insulin stimulates glucoseView drug information transport, glucoseView drug information metabolism, and glycogen synthesis. Insulin also increases cellular uptake of amino acidsView drug information and stimulates protein synthesis (Fig. 20.3).
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