GSK3 Beta :: essays research papers

air division IScientific Rationale for Selection of the levelA.Characterization of TargetDiabetes Mellitus is a heterogeneous group of metabolic diseases characterized by the presence of immoderate amounts of glucose and glucagon in the blood of diabetic patients. The most frequently cited reason for Diabetes Mellitus (DM) is each a lack of insulin secretion (DM Type I) and/or, more commonly, the resistance to insulin in the peripheral tissues, particularly muscle and adipose tissue (DM type II). Hence, insulin has presbyopic been a target for the treatment of DM. In DM Type I, endovenous or subcutaneous insulin injection has often been the norm. Iatrogenic insulin administration, insulino-mimetics, or insulin-secretagogues strike been the major modalities of treatment for DM type II however, these treatments do non address the resistance in peripheral tissues to insulin. Essentially, these modes offer a brute-force method of treating hyperglycemia, by increasing levels of a decreasingly effective hormone (Champ).Under ruler physiological conditions, insulin binds to the insulin receptor and becomes phosphorylated as a result. The phosphorylated insulin receptor binds to and phosphorylates IRS proteins and Shc, which bind differentially to various downstream signaling proteins. Phosphatidylinositol 3-kinase (PI3-kinase), a downstream effector of IRS, is critical for the metabolic action of insulin - glucose transport, animal starch price reduction, and protein synthesis (FIGRURE 1) (Virkamaki). It has been discovered that protein kinase B (PKB), a downstream target of PI3-kinase directly phosphorylates and, as a result, inhibits glycogen synthase kinase-3 (GSK-3). GSK-3 is a kinase, present in two nearly identical isoforms (GSK 3a and GSK 3b), which ar constitutively active in resting cells of various tissues. When active, GSK-3 phosphorylates and inhibits, glycogen synthase, effectively blocking the synthesis of glycogen and favoring the presence of glucose monomers in the blood. GSK-3 also phosphorylates and inhibits IRS-1, the presence of which is associated with insulin resistance (Eldar). Furthermore, GSK-3, which is obligated for blocking the synthesis of glycogen, is inhibited by insulin and therefore, effectively acts as a GSK-3 inhibitor. During peripheral resistance of insulin, as seen in DM type II patients, GSK-3 is no longer through binding of insulin to its receptor. Purportedly, GSK-3 limits insulin action via serine phosphorylation of IRS-1 and it also inhibits glycogen synthase by the same mechanism. Hence by inhibiting IRS-1, PI3K is no longer activate to inhibit GSK-3. Essentially, GSK-3 triggers a negative feedback mechanism that results in its own disinhibition. (FIGURE 2) impertinent methods in the treatment of DM type II, involves targeting the signaling pathway of insulin kinda than increasing insulin concentrations in a patient.