Insulin Protein synthesis

The insulin receptor is a transmembrane receptor tyrosine kinase located in the plasma membrane of insulin-sensitive cells (e.g., adipocytes, myocytes, hepatocytes). It mediates the effect of insulin on specific cellular responses (e.g., glucose transport, glycogen synthesis, lipid synthesis, protein synthesis). 

Other, more general effects of insulin on cellular function include stimulation of cell growth (increase in DNA and protein synthesis), inhibition of apoptosis, and modulation of ion-channel activity. 

Under normal feeding patterns the rate of tissue protein catabolism is more or less constant throughout the day it is only in cachexia that there is an increased rate of protein catabolism. There is net protein catabolism in the postabsorptive phase of the feeding cycle and net protein synthesis in the absorptive phase, when the rate of synthesis increases by about 20-25%. The increased rate of protein synthesis is, again, a response to insulin action. Protein synthesis is an energy-expensive process, accounting for up to almost 20% of energy expenditure in the fed state, when there is an ample supply of amino acids from the diet, but under 9% in the starved state. 

Herbert, T. P., Kilhams, G. R., Batty, I. H., and Proud, C. G. (2000). Distinct signaling pathways mediate insulin and phorbol ester-stimulated eIF4F assembly and protein synthesis in HEK 293 cells. J. Biol. Chem. 275, 11249—11256. 

There are 20 amino acids found in the human body that are involved in protein synthesis. Refer to your textbook for a table of the 20 amino acids. The sequence of the amino acids dictates the properties of a protein. Examples of proteins include keratin in hair, hemoglobin, insulin, antibodies, and enzymes. 

One could plunge into the steric problems posed by the mechanism of protein synthesis on the ribosome 25 26)> or consider the steric fit of the hormone insulin to its acceptor in the cell membrane 27>. Or one could delve into the beautiful intricacy of terpenoid, squalene and steroid metabolism, or get lost in double bond formation, or in the steric problems posed by the branched chain fatty acids and their derivatives 28-34). 

Insulin promotes amino acid uptake and protein formation. AKT, noted above, is also implicated in mechanisms which regulate protein synthesis. Acting via GSK-3 again, under basal conditions, GSK-3 phosphorylates a key protein translation regulator (called eIF2B). Thus, if GSK-3 is inactivated, eIF2B is not phosphorylated and mRNA translation is permitted. 

The major fuels of skeletal muscle are glucose and fatty acids. Because of the enormous bulk, skeletal muscle is the body s major consumer of fuel. After a meal, under the influence of insulin, skeletal muscle takes up glucose to replenish glycogen stores and amino acids that are used for protein synthesis. Both excess glucose and amino acids can also be oxidized for energy. 

Muscle All the amino acids are required for protein synthesis so that the transporters are important particularly during growth. Consistent with this, the major anabolic hormone, insulin, increases the transport of some amino acids into the muscle, which contributes to the stimulation of protein synthesis by insulin. 

Figure 12.17 Sites at which insulin stimulates protein synthesis in a muscle. The sites are indicated by 0. Insulin has its anabolic effect on protein synthesis in muscle by affecb ng six processes or reactions (i) it inhibits protein degradab on in the muscle (ii) it sb mulates amino acid transport from the blood into the muscle (iii) it stimulates the inib ab on-reacb on of the pathway for protein synthesis, i.e. formab on of the complex (tRNA-amino acid-mRNA-ribosomal RNA) (iv) it increases the rate of mRNA synthesis, and therefore the number of mRNA molecules (v) it stimulates ribosomal RNA synthesis (vi) it sb mulates elongabon of the pepbde (see Chapter 20).

Some of the effects of insulin on the carbohydrate metabolism (right part of the illustration) are possible without protein synthesis. In addition to Grb-2, another dimeric adaptor protein can also bind to phosphorylated IRS. This adaptor protein thereby acquires phos-phatidylinositol-3-kinase activity (PI3K) and, in the membrane, phosphorylates phospholi-... 

Il.f.l.1. Insulins. Insulin is the most effective of diabetes medications. Insulin has profound effects on carbohydrate, protein, fat metabolism and electrolytes. It has anabolic and anticatabolic actions. In a state of insulin deficiency, glycogenesis, glucose transport, protein synthesis, triglyceride synthesis, LPL activity in adipose tissue, cellular potassium uptake all decrease on the other hand, gluconeogene-sis, glycogenolysis, protein degradation, ketogene-sis, lipolysis increase. 

Mechanism of Action A polypeptide hormone that stimulates cartilaginous growth areas of long bones, increases the number and size of skeletal muscle cells, influences the size of organs, and increases RBC mass by stimulating erythropoietin. Influences the metabolism of carbohydrates (decreases insulin sensitivity), fats (mobilizes fatty acids), minerals (retains phosphorus, sodium, potassium by promotion of cell growth), and proteins (increases protein synthesis). Therapeutic Effect Stimulates growth. 

The demonstration that protein synthesis is required for lL-1-induced inhibition of insulin secretion stimulated a number of studies directed at examining proteins whose synthesis is modulated by lL-1. The synthesis of a number of islet proteins has been shown to be stimulated by IL-1 (Hughes et al., 1990a Sandler et al., 1991 Helqvist et al., 1989 Welsh et al., 1991b). Treatment of islets for... 

Eizirik, D. L., Cagliero, E., Bjorklund, A., and Welsh, N. (1993). Interleukin-1-induced expression of nitric oxide synthase in insulin-producing cells is preceded by c-fos induction and depends on gene transcription and protein synthesis. FEBS Lett. 317, 62-66. 

Insulin promotes synthesis (from circulating nutrients) and storage of glycogen, triglycerides, and protein in its major target tissues liver, fat, and muscle. The release of insulin from the pancreas is stimulated by increased blood glucose, incretins, vagal nerve stimulation, and other factors (see text). 

Effects on protein synthesis In most tissues, insulin stimulates the entry of amino acids into cells, and protein synthesis. 

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