Role in Glucose Metabolism Discussion

Role in Glucose Metabolism The glucose metabolism balance is executed through the signalling cascades; the first being the glucose stimulated insulin secretion and the second cascade is insulin mediated glucose uptake. The second cascade permits the insulin to elevate the glucose uptake through adipose tissue and skeletal muscle, in addition it will even supress the generation of glucose by the cells of liver.

When insulin interacts with the insulin receptor’s alpha subunit that are present outside the cell or on celullar surface, the activation of the insulin cascade’s downstream signalling begins. This activation can result in the conformational changes in the insulin-receptor complex, which eventually causes phosphorylation of tyrosine kinase in the insulin receptor substrates and also activates of phosphatidylinositol-3-kinase. These events bring about the translocation of GLUT-4 transporter from intracellular to extracellular on the skeletal muscle cell’s plasma membrane. In the cell, GLUT4 is present within vesicles. The rate at which GLUT4-vesicles undergo exocytosis increases because of insulin’s actions. Therefore, by increasing GLUT-4’s presence on the plasma membrane, the insulin allows inward movement of glucose into skeletal muscle cells for metabolism into glycogen.

• Role in Glycogen Metabolism Insulin has a significant function in the stimulation of production of glycogen in the liver. Protein phosphatase I (PPI) is the most important molecule in the management of glycogen metabolism. By dephosphorylation, PPI exihibits reduction in the rate of glycogenolysis by inactivating phosphorylase kinase, and phosphorylase A. PPI fastens glycogenesis by activating glycogen synthase B. Insulin helps to increase PPI substrate-specific activity on glycogen molecules and so in turn stimulating the synthesis of glycogen from glucose in the liver.

There are many hepatic/ liver based metabolic enzymes that under the influence of insulin through gene transcription—this show effect in gene expression in the metabolic pathways. In gluconeogenesis, insulin inhibits the gene expression of phosphoenolpyruvate carboxylase, fructose-1, 6-bisphosphatase and glucose-6-phosphatase. In the glycolysis process, gene expression of glucokinase and pyruvate kinase increases. In lipogenesis, the gene expression of fatty acid synthase, pyruvate dehydrogenase, and acetyl-CoA carboxylase is increased.

• Role in Lipid Metabolism Insulin elevates the expression of few lipogenic enzymes. This is because of glucose stored as a lipid that is present inside adipocytes. Therefore, an increase in a fatty acid production will increase glucose take in by the cells. Insulin furthermore dephosphorylates and inhibits hormone-sensitive lipase, which leads to prevention of lipolysis. Thus, insulin reduces the amount of serum free fatty acid levels.

• Role in Protein Metabolism Rate of protein turnover is managed in part by insulin. Production of protein is promoted by insulin’s increase in intracellular uptake of several amino acids like alanine, arginine, and glutamine along with gene expression of albumin and muscle myosin heavy chain alpha. The regulation of protein breakdown is affected by insulin’s downregulation of hepatic and muscle cell enzymes responsible for protein degradation. The enzymes which are impacted include ATP-ubiquitin-dependent proteases, ATP-independent lysosomal proteases and hydrolases.

• Role in Inflammation and Vasodilation In the macrophages and the endothelial cells, the insulin action shows an effect on the body which is anti-inflammatory. The insulin gives signal for the endothelial nitric oxide synthase expression in the endothelial cells. eNOS function is to release nitric oxide (NO), which causes vasodilation. Insulin shows suppression of nuclear factor-kappa-B (NF-kB) which is found inside the endothelial cells. The nuclear factor kappa B of the endothelial cells initiates the adhesion molecules expression like Intercellular Adhesion Molecule-1 and E-selectin, that secretes into the circulation, the cell adhesion molecules which are soluble. Insulin helps in the suppression of the generation of O2 radicals and reactive oxygen species (ROS). The insulin stops NADPH oxidase expression by suppressing one of the essential components of the macrophage, called as p47 phox. The NADPH oxidase assists in oxygen radical production, which gives the signal to nuclear factor kappa b kinase beta inhibitor. The nuclear factor kappa b kinase beta inhibitor phosphorylates the Inhibitory kappa B leading to its disruption. This secretes Nuclear Factor kappa light chain enhancer of activated B cells that will permit the translocation in the nucleus of macrophage. The Nuclear Factor kappa light chain enhancer of activated B cells in the nucleus will give the signal for the transcription of the gene encoding for proteins that are secreted in the circulation and are pro-inflammatory in nature.