Insulin is a peptide hormone secreted in the body by beta cells of islets of Langerhans of the pancreas and regulates blood glucose levels. Medical treatment with insulin is indicated when there is inadequate production or increased insulin demands in the body. Insulin is responsible for the regulation of glucose levels in the body. It stimulates the storage of energy and inhibits the breakdown of high energy metabolites. Insulin acts by directly binding to its receptors on the plasma membranes of the cells. These receptors are present on all the cells, but their density depends on the type of cells, with the maximum density being on the hepatic cells and adipocytes. The insulin receptor is a heterotetrameric glycoprotein consisting of two subunits, the alpha and the beta subunits. The extracellular alpha subunits have insulin binding sites. The beta subunits, which are transmembranous, have tyrosine kinase activity. When insulin binds to the alpha subunits, it activates the tyrosine kinase activity in the beta subunit, which causes the translocation of glucose transporters from the cytoplasm to the cell's surface. Insulin promotes glycogen synthesis, lipid synthesis, protein synthesis, DNA synthesis, and cellular growth and differentiation. Once glucose gets absorbed from a meal, it enters the blood, and then the pancreas releases insulin. Insulin synthesis occurs in the beta cells of the pancreas initially as preproinsulin. Preproinsulin then converts to proinsulin, which then transforms into a single peptide with A, B, and C peptide units. The A and B peptides are joined by disulfide bonds to make insulin and are secreted into the bloodstream. Insulin binds to its cellular receptor. The insulin receptor is composed of alpha subunits, beta subunits, and a tyrosine kinase enzyme. When insulin binds to the alpha subunit, this triggers phosphorylation and activation of the target proteins intracellularly by the tyrosine kinase leading to many effects on cellular metabolism. Activation of the insulin receptor also leads to increased expression of GLUT (a glucose transporter) to the membrane surface and promotes the entry of glucose to the intracellular compartment and then undergoes cellular metabolism. Insulin signals glucose conversion to glycogen for storage and the formation of acetyl coenzyme A and triacylglycerol, which get stored in adipose tissue. Also, insulin directs amino acids for protein synthesis. Pancreatic β-cell dysfunction plays an important role in the pathogenesis of both type 1 and type 2 diabetes. Insulin, which is produced in β-cells, is a critical regulator of metabolism. Insulin is synthesized as preproinsulin and processed to proinsulin. Proinsulin is then converted to insulin and C-peptide and stored in secretary granules awaiting release on demand. Insulin synthesis is regulated at both the transcriptional and translational level. The cis-acting sequences within the 5′ flanking region and trans-activators including paired box gene 6 (PAX6), pancreatic and duodenal homeobox-1(PDX-1), MafA, and B-2/Neurogenic differentiation 1 (NeuroD1) regulate insulin transcription, while the stability of preproinsulin mRNA and its untranslated regions control protein translation. Insulin secretion involves a sequence of events in β-cells that lead to fusion of secretory granules with the plasma membrane. Insulin is secreted primarily in response to glucose, while other nutrients such as free fatty acids and amino acids can augment glucose-induced insulin secretion. In addition, various hormones, such as melatonin, estrogen, leptin, growth hormone, and glucagon like peptide-1 also regulate insulin secretion. Thus, the β-cell is a metabolic hub in the body, connecting nutrient metabolism and the endocrine system. Although an increase in intracellular [Ca2+] is the primary insulin secretary signal, cAMP signaling-dependent mechanisms are also critical in the regulation of insulin secretion.

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