Production of Insulin in the Body - Term Paper Example

Insulin is a hormone used in the body to regulate the amount of glucose in the blood and a wide range of other physiological processes. Thehormone is released in the body when there is an elevated level of glucose in the blood plasma. Upon its release in the blood stream, the muscles and the liver increase glucose uptake and its conversion to glycogen (Rhodes and White 4). Production of insulin in the body stops glycogenolysis and gluconeogenesis. Glycogenolysis is a metabolic process that involves the conversion of glycogen into glucose monomers. Similarly, gluconeogenesis is a process that produces glucose from simpler molecules, such as glycerol, lactate and pyruvate (Rhodes and White 5). The termination of gluconeogenesis and glycogenolysis results to restoration of normal glucose levels in the blood. The action of insulin in the body is usually brief and the level blood sugar changes after the action of insulin subsides. Besides the control of blood sugar, production of insulin initiates a series of metabolic reactions that are mainly mediated by the changes in expression of over 100 genes in the body (O’Brien and Granner, 1117). One of the major effects of insulin in such physiological processes includes the regulation in the expression of genes that stimulate absorption of amino acids, metabolisms of lipids mainly in the muscles and adipose tissue. In addition, insulin affects the expression of genes used for growth, development and survival of somatic cells (Rhodes and White8) Introduction Alfred Sanger did the first sequencing of amino acids that make up insulin hormone in 1955 (BCBC 1). According to BCBC (1) insulin is the first protein to have its amino acid chain determined and sequenced. Moreover, the hormone is the first “peptide protein measured by radioimmunoassay technique”. In addition, insulin is the first hormone to be produced in microorganisms using recombinant DNA technology, a process that was successfully conducted in the 1970s. Since then, insulin produced by recombinant DNA technology has been used for treating diabetes, replacing earlier hormones that were produced from purification of insulin from animal species (BCBC1) Disruption of insulin synthesis in the body causes several physiological changes in the body. One of the major impacts of low glucose production is hyperglycemia, a medical condition characterized by an abnormal increase of glucose in the blood plasma (Steiner and James 42). Other effects include poor growth and development of the body. Diabetic patients manifest the high blood sugar level in the body. The accumulation of high level of blood sugar in diabetic individual causes complex health problems, including blindness, kidney malfunction, heart diseases, poor nervous coordination and erectile dysfunction in men. In addition, people suffering from diabetes have poor recovery of wounds, leading to amputations of the affected limbs (Steiner and James 44). According to Rhodes and White, maintenance of normal blood glucose level in the body is undertaken through a strictly controlled and coordinated mechanism in the secretion and subsequent action of the insulin hormone (9). The Structure of insulin One insulin molecule performs like a bivalent ligand to insulin receptors through two binding surfaces (BCBC 2). According Chang et al (9413), insulin molecule comprises of two peptide chains, namely A and B. The two peptide chains are joined by the two disulfide bonds. The disulfide bond link the two chains covalently. Peptide chain A contains an additional internal disulfide bond. In mammalian insulin, the location of the three disulfide bonds are the same. The structure of insulin differs from one species to another, in most species including human beings, chain B is made up of 30 amino acids while A comprises of 21 amino acids. In addition, the two ends of the chain A and the C- terminal residue of the B chain are maintained in insulin of all species (Chang, et al, 9413-23). The resulting structural composition of insulin forms a three dimensional conformation that is similar in most species. Therefore, insulin from one species has a high probability of being biologically active in a different animal. In normal circumstances, insulin that is biologically active and circulating in the plasma is monomeric in nature (BCBC 2). At very low concentrations, the insulin molecule forms dimers because of formation of hydrogen bonds between the C terminus of the B chain. In presence of zinc ions, dimers in the insulin structure associate to form hexamers. The molecular weight of insulin molecule is about 6000 Daltons (BCBC 2). The three dimensional structure of insulin hormone comprises of three helixes and disulfide links (Rhodes and White 13). The protein molecule is highly stable in the three dimensional structure because of hydrophobic residues forming the central part of the hormone. The core of the protein is surrounded by two non-polar surfaces. One of the non-polar surfaces is flat, aromatic and is located on the dimers. The position of the flat and non-polar surface forms a parallel and beta sheet structure. The second flat surface is widespread in the molecule and is mainly prevalent in hexamer conformation (Chang, et al, 9427) Production of insulin Insulin is produced in the pancreas by the beta cells. The process of insulin production is initiated by the translation of the insulin mRNA in form of a single sequence precursor referred as preproinsulin (Chang, et al, 9432). During the insertion process of the insulin into the endoplasmic reticulum, the peptide signal on preproinsulin is removed forming proinsulin. According to Rhodes and White (14), the structure of proinsulin comprises of three components, namely a carboxy terminal on A peptide chain, an amino end on the peptide B and a central section referred as peptide C. While in the endoplasmic reticulum, the action of endopeptidases enzymes removes peptide C from the proinsulin, resulting to the formation of the complete insulin molecule. Insulin is repackaged in the Golgi apparatus, from where it is transferred to the secreting glands located in the cytoplasm. The beta cells within the islets of Langerhans are excitable and triggered by various stimulating factors to secrete insulin (Adler, et al 850). According to Adler et al, beta cells secrete insulin through the process of exocytosis (853).Through diffusion, the secreted insulin enters into blood capillaries located in the pancreas and eventually into the circulatory system. Various stimuli trigger secretion of insulin from the beta cells. Some of the stimulants include the changing concentration of glucose in the cells. According to Adler, et al (867), low glucose concentration makes the cells to become hyperpolarized. High glucose concentration triggers the action potential that depolarizes the membrane on the cells. This causes the opening of calcium channels on the cells and the calcium ions enters into the cell causing exocytosis that release insulin (Steiner and James, 46). Other factors that stimulate secretion of insulin include neural stimuli, such as the sight and smell food. In addition, high concentration of energy producing molecules such as amino acids and glycerol stimulates secretion of insulin from the beta cells (Steiner and James, 53). Mechanism of insulin action in the body After secretion of insulin from the beta cells and subsequent diffusion in the blood plasma, insulin lowers the concentration of blood sugar in a series of complicated processes (Adler, et al, 892) The hormone facilitates uptake of glucose in several tissues, including muscles and adipose tissue. Glucose is absorbed by the tissues through diffusion that is facilitated by glucose transporters such as GLUT4. Insulin stimulates production of glucose transporters in the cell membrane. GLUT4 glucose transporters are usually stored in cytoplasmic vesicles and in this location; they are incapable of transporting glucose unless they are stimulated by insulin (Rhodes, and White 12). When insulin binds on the receptors of glucose transmitters in the cytoplasmic vesicles, it promotes fusion of the vesicles with plasma membrane on which the transporters are inserted. This process accords the cell ability to absorb glucose. When the concentration of insulin decreases, the glucose transporters are transferred back to the cytoplasmic vesicles. The liver has its own glucose transporters that absorb glucose without the need of insulin stimulation (O’Brien and Granner, 1111-16). In the liver, insulin triggers the organ to store glucose in form of glycogen. According to Adler et al hepatocytes cells, which are located in the liver, absorbs glucose from the intestines converting it into glycogen (897). The reaction below shows the action of the insulin in conversion of glucose into glycogen in the liver. Two enzymes, namely glycogen synthase and phosphofructokinase are essential for the reaction. To stimulate the conversion of glucose into glycogen in the liver, insulin activates hexokinase, an enzyme that phosphorylates glucose retaining it in the cell. Insulin also activates phosphofructokinase and glycogen synthase, enzymes that enhance the conversion of glucose into glycogen. The glycogen is then stored in the liver. When the amount of glycogen in the liver exceeds the required amount, insulin stimulates the conversion of excess glycogen into fatty acids, which are carried away from the liver in form of lipoproteins, in form of fatty acids. The fatty acids are released for circulation in the body and are essential components for use in adipocytes cells for the synthesis of triglycerides (O’Brien and Granner, 1114-23) The release of insulin hormone prevents the breakdown of the fat stored in the adipose tissue. The hormone inactivates intracellular lipase enzyme that normally converts triglycerides in a hydrolytic reaction to produce fatty acids. Moreover, insulin stimulates the transfer of glucose in the adipocytes where it is converted into glycerol. The glycerol in conjunction with fatty acids synthesized from the liver reacts to form triglycerides in the adipose tissues (O’Brien and Granner, 1134). Therefore, besides lowering the concentration of sugar in the blood, insulin promotes the storage of fats in the adipose tissues. Fat accumulation in the adipose tissue is stimulated by the preferential oxidation of carbohydrates rather than fatty acids in order to release energy. Conclusion I chose the topic on insulin because of its medical importance. Diabetes develops when pancreas fails to produce insulin. According to Adler et al (900), there are two types of diabetes, including type 1 and 2. Type 1 diabetes is characterized by complete failure of the liver to produce insulin. Therefore, people with this type of diabetes require a daily intake of artificial insulin. Type 2 diabetes results from progressive reduction in secretion of insulin and resistance of body to action of the hormone. Diabetes is one of the leading causes of death globally (Adler, et al 904). Therefore understanding the functioning and mechanism of insulin is important in order to promote understanding on the best management and control practices of the disease. The structure and functioning of insulin hormone is relevant to chemistry discipline for various reasons. First, understanding the structure of the hormone could enhance artificial synthesis of insulin in the laboratory. Equally important, the different structures of insulin hormone affect its efficacy in the clinical practice of diabetes management. Monomeric and dimeric structures diffuse easily in the blood plasma while the rate of diffusion of hexamer structure is poor (Chang, et al, 9421). This implies that the treatment process of a patient with hexameric insulin is slow. Therefore, the chemical knowledge of these structures is essential to enable biochemists and pharmacists design more effective insulin derivatives. Insulin hormone is a protein in nature and it functions by activating enzymes. Therefore, the knowledge is essential in chemistry in order to elucidate the conditions necessary for its activity in the body. Work Cited Adler, AI., et al. “UKPDS 59: Hyperglycemia and Other Potentially Modifiable Risk Factors for Peripheral Vascular Disease in Type 2 Diabetes.” Diabetes Care, 25(2002): 890-900. BCBC (Beta Cell Biology Consortium). “The structure of insulin.” 2002. 11 December 2011. http://www.betacell.org/content/articles/?aid=8 Chang, X.,et al. “Solution Structures of the R6 Human Insulin Hexamer.” Biochemistry, 36.31(1997): 9410-22. O’Brien, R., and Granner, D. “Regulation of Gene Expression by Insulin.” Physiol Rev, 76(1996): 1106-65. Rhodes, C., and White, M. “Molecular Insights into Insulin Action and Secretion.” European Journal of Clinical Investigation, 32.3(2002): 3-14. Steiner, D., and James, D. “Cellular and Molecular Biology of the Beta Cell.” Diabetologia 35 Suppl 2(1992): 41-48. Read More