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Insulin is a peptide hormone that is made in the beta cells of the islets of Langerhans in the

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Insulin is a peptide hormone that is made in the beta cells of the islets of Langerhans in the pancreas. Insulin regulates the influx of glucose and lipid metabolism in the liver, while it inhibits fatty acid oxidation, glycogenolysis, and gluconeogenesis. Insulin is comprised of 2 polypeptides, 51 amino acids and a molecular weight of 5808 Da. These two chains are coupled together by disulphide bridges (Bell et al., 1980), chains A is composed of 21 amino acids and B with 30 amino acids in its chain. Insulin is manufactured in the β cells in the form of pre-proinsulin. Immediately after syntheses pre-proinsulin is released into the rough endoplasmic reticulum where it is cleaved by proteolytic enzymes to form proinsulin. Proinsulin, the A …show more content…

As mentioned, insulin is a premier hormone in the regulation of blood glucose levels; however, resistance to insulin stimulation is a common phenomenon and plays a critical role in the pathogenesis of several human diseases. Himsworth first demonstrated the fact that a sufficient amount of the patients with diabetes are “insulin insensitive” about 50 years ago; on the basis of this finding, he suggested that patients with diabetes are either insulin sensitive or insulin insensitive (Himsworth, 1936).

Recent research has shown that insulin resistance is linked to defects in several proteins involved in metabolism and/or the immune response pathway. Mice lacking the Ir (insulin receptor) gene displayed a small growth defect; however they promptly developed hyperglycemia and hyperinsulinemia (Accili et al. 1996). Recently, (Guo, 2014) demonstrated that removing both the Irs1 and Irs2 receptor genes in the liver of mice, prevented the activation of hepatic Akt→Foxo1 phosphorylation, which resulted in the development of hyperglycemia, hyperinsulinemia, insulin resistance, and hypolipidemia. These results suggest that Irs1 and Irs2 are key proteins critical to the normal functioning of the insulin-signaling pathway. It was also shown in this same experiment that the deletion of Irs1 and Irs2 are associated with the inactivation PI3K and Akt, two other proteins involved in the uptake of glucose. Activation of PI3K and Akt plays a central

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