Insulin signaling

Calpain-10 (CAPN10) is the fust diabetes gene to have been identified through a genome scan. The discovery of calpain-10 has identified it as a molecule of importance to insulin signaling and secretion that may have relevance to the fiiture development of novel therapeutic targets for the treatment of type 2 diabetes. 

Koumanov F, Jin B, Yang J et al (2005) Insulin signaling meets vesicle traffic of GLUT4 at a plasma-membrane-activated fusion step. Cell Metab 2 179-189... 

Withers DJ, White M (2000) Perspective the insulin signaling system - a common link in the pathogenesis of type 2 diabetes. Endocrinology 141 1917-1921... 

The holochromodulin binds to the insulin-stimulated insulin receptor, helping to maintain its active conformation and increasing insulin signaling. 

In both types of diabetes, however, this normal process malfunctions. A gland called the pancreas, found just behind the stomach, makes insulin. In people with insulin-dependent diabetes, the pancreas does not produce insulin at all. This condition usually begins in childhood and is known as Type I (formerly called juvenile-onset) diabetes. These patients must have daily insulin injections to survive. People with non-insulin-dependent diabetes usually produce some insulin in their pancreas, but their bodies tissues do not respond well to the insulin signal and, therefore, do not metabolize the glucose properly, a condition known as insulin resistance. 

SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRSl and 1RS2. / Biol Chem 2002, 277, 42394-8. 

The increased oxidation of fatty acids decreases the rate of glucose utilisation and oxidation by muscle, via the glucose/fatty acid cycle, which accounts for some of the insulin resistance in trauma. An additional factor may be the effect of cytokines on the insulin-signalling pathway in muscle. An increased rate of fatty acid oxidation in the liver increases the rate of ketone body production the ketones will be oxidised by the heart and skeletal muscle, which will further reduce glucose utilisation. This helps to conserve glucose for the immune and other cells. 

With respect to glycaemic parameters FXR-deficient mice (FXR ) show impaired glucose tolerance, whole-body glucose disposal and insulin resistance. FXR deficiency is also associated with impaired distal insulin signalling in muscle and WAT through reduced insulin-dependent AKT phosphorylation. ... 

Geeraert B, Crombe F, Hulsmans M, Benhabiles N, Geuns JM, Holvoet P. (2010) Stevioside inhibits atherosclerosis by improving insulin signaling and antioxidant defense in obese insulin resistant mice. Int J Obes 34 569-577. 

---