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Sending the signal: molecular mechanisms regulating glucose uptake


, : Sending the signal: molecular mechanisms regulating glucose uptake. Medicine and Science in Sports and Exercise 36(7): 1212-1217

The molecular signaling mechanisms by which insulin leads to increased glucose transport and metabolism and gene expression are not completely elucidated. We have characterized the nature of insulin signaling defects in skeletal muscle from Type 2 diabetic patients. Insulin receptor substrate (IRS-1) phosphorylation, phosphatidylinositol (PI) 3-kinase activity, and glucose transport activity are impaired as a consequence of functional defects, whereas insulin receptor tyrosine phosphorylation, mitogen-activated protein kinase (MAPK) phosphorylation, and glycogen synthase activity are normal. Using biotinylated photoaffinity labeling, we have shown that reduced cell surface GLUT4 levels can explain glucose transport defects in skeletal muscle from Type 2 diabetic patients under insulin-stimulated conditions. Current work is focused on mechanisms behind insulin-dependent and insulin-independent regulation of glucose uptake. We have recently determined the independent effects of insulin and hypoxia/AICAR exposure on glucose transport and cell surface GLUT4 content in skeletal muscle from nondiabetic and Type 2 diabetic subjects. Hypoxia and AICAR increase glucose transport via an insulin-independent mechanism involving activation of 5'-AMP-activated kinase (AMPK). AMPK signaling is intact, because 5-aminoimidazole-4-carboxamide 1-beta-D-ribonucleoside (AICAR) increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation to a similar extent in Type 2 diabetic and nondiabetic subjects. However, AICAR responses on glucose uptake were impaired. Our studies highlight important AMPK-dependent and independent pathways in the regulation of GLUT4 and glucose transport activity in insulin resistant skeletal muscle. Understanding signaling mechanisms to downstream metabolic responses may provide valuable clues to a future therapy for Type 2 diabetes.

US$19.90

PMID: 15235328

DOI: 10.1249/01.mss.0000132387.25853.3b


Other references

Kawahara, R., 2012: Validation therapy, others. Nihon Rinsho. Japanese Journal of Clinical Medicine 69 Suppl 10 Pt 2: 136-140

Bogdanov, R.R.; Kotov, S.V.; Kunitsyna, A.N.; Turbina, L.G., 2011: Pharmacotherapy of motor manifestations in late stages of Parkinson's disease. Accumulating data on experience of long therapy with levodopa revealed the pathomorphosis of clinical presentations of Parkinson's disease during its progression, in particular, described, the occurrence of motor fluctuations and levodopa-ind...

Karrer, W., 1990: Tuberculosis--prevention. Diagnostic and therapeutic measures. The most effective prevention of an infectious disease is the correct treatment of patients already affected. While dealing with infected tuberculosis patients one has to take hygienic measures in order to protect doctors and nursing staff as well...

Wilson, R.I.; Dengler, L.A.; Legg, M.R.; Long, K.; Miller, K.M., 2010: The 2010 Chilean tsunami on the California coastline. Seismological Research Letters 81.3

Vlanti, A.; Diallinas, G., 2008: The Aspergillus nidulans FcyB cytosine-purine scavenger is highly expressed during germination and in reproductive compartments and is downregulated by endocytosis. We cloned and characterized an Aspergillus nidulans gene, called fcyB, encoding the closest homologue to the yeast Fcy2p/Fcy21p permeases. Deletion of fcyB (Delta fcyB) does not affect growth, development, reproduction or bulk purine uptake, but...

Bhattacharjee, S., 2016: Emerging trend of advanced image analysis in nanomedicine. Nanomedicine 10(18): 2801-2804

Hinz, O.S., 1956: A simple colorimetric micromethod for estimating protein in biological material. Total protein was estimated in 0 02 ml. of the test solution by air-drying on a glass plate of 15 mm. diameter, staining with Amido black 10 B, washing off excess dye with acetic acid in methano and eluting the dyed protein in 0.1N NaOH for measur...

Mervis, Jeffrey, 1996: Breaking the ice on cooperation. The top priority for U.S. oceanographers is a new Arctic research vessel. The oceanographers believe that this vital region needs a vessel dedicated to exploring fundamental questions ranging from marine geology and world ocean circulation to Arct...

Berrance, N., 1964: The Respiratory Resuscitation Center. Its Advantages In Hospital Practice. Jornal do Medico 54: 316-325

Thompson, A.M., 1964: The Literature Of Nursing. Bulletin of the Medical Library Association 52: 427-437