Lipids insulin sensitivity

The insulin receptor is a transmembrane receptor tyrosine kinase located in the plasma membrane of insulin-sensitive cells (e.g., adipocytes, myocytes, hepatocytes). It mediates the effect of insulin on specific cellular responses (e.g., glucose transport, glycogen synthesis, lipid synthesis, protein synthesis). 

In summary, results from several studies in to the effects of impaired insulin action can now be linked to CVD. Because of the numbers of people exhibiting sings of insulin resistance, there has been a lot of research effort has gone in to finding suitable therapeutic interventions. One group of drugs in particular, the thiazolidinediones (also known as glitazones) has attracted attention because they both increase insulin sensitivity and help to normalize plasma lipid concentrations. 

A brief overview about the fundamental principles of the pathogenesis of skeletal muscle insulin resistance and its contribution to the development of type 2 diabetes mellitus is given in the following. Priority is given to the role of lipid metabolism, which is the main field of the reported spectroscopic studies. Furthermore, the technique of euglycemic hyperinsulinemic glucose clamp is described allowing determination of the individual insulin sensitivity of musculature. The role of IMCL in insulin resistance of the skeletal muscle is discussed. 

The lipid infusion protocol represents an experimental situation with supraphysiologically high NEFA blood levels. In the following study it was examined, whether an extrapolation of the results to physiological situations is possible. For this purpose, the effects of short term dietary interventions on IMCL levels and insulin sensitivity were studied. Twelve healthy, lean male subjects with intermediate insulin sensitivity (BMI 23.2 0.6 kg/m, GIR = 46.1+2.8 pmol/kg/min received a high caloric (HC) and a normal caloric (NC) diet. The diets had a duration of 3 days and were characterized as follows ... 

Peterson et al. found an increase in intramyocellular lipid content and reduction in mitochondria phosphorylation (mitochondrial rates of ATP production) in insulin-resistant subjects versus insulin-sensitive subjects. They concluded that their results supported the h) othesis that insulin resistance is due to dysregulation of intramyocellular fatty acid metabolism, which maybe caused by an inherited defect in mitochondrial oxidative phosphorylation. 

It effectively controls blood pressure over 24 hours suppressing early morning BP rise. It increases insulin sensitivity, improves lipid profile. 

J. R (2001) Improved lipid and lipoprotein profile, hepatic insulin sensitivity, and glucose tolerance in llfi-hydroxysteroid dehydrogenase type 1 null mice. /Biol Chem 276, 41293-41300. 

Tan MH, Johns D, Strand J, Hlse J, Madsbad S, Eriksson JW, Clausen J, Konkoy CS, Herz M, for the GLAC Study Group. Sustained effects of pioglitazone vs. glibenclamide on insulin sensitivity, glycaemic control and lipid profiles in patients with type 2 diabetes. Diabetic Med 2004 21 859-66. 

Bareille P, Azcona C, Matthews DR, Conway GS, Stanhope R. Lipid profile, glucose tolerance and insulin sensitivity after more than four years of growth hormone therapy in non-growth hormone deficient adolescents. Clin Endocrinol (Oxf) 1999 51(3) 347-53. 

Weinberger MH. Mechanisms of diuretic effects on carbohydrate tolerance, insulin sensitivity and lipid levels. Eur Heart J 1992 13(Suppl G) 5-9. 

Murakami, K., Tobe, K., Ide, T., Mochizuki, T., Ohashi, M., Akanuma, Y., Yazaki, Y., and Kadowaki, T. (1998). A novel insulin sensitizer acts as a coligand for peroxisome proliferator-Activated Receptor-Alpha (PPAR-alpha) and PPAR-Gamma Effect of PPAR-Alpha Activation on Abnormal Lipid Metabolism in Liver of Zucker Fatty Rats. Diabetes AT, 1841-1847. 

Kemnitz, M. W., Elson, D. F., Roecker, E. B., Baum, S. T., Bergman, R. N., and Meglasson, M. D. (1994). Pioglitazone Increases Insulin Sensitivity, Reduces Blood Glucose, Insulin, and Lipid Levels, and Lowers Blood Pressure in Obese, Insulin-Resistant Rhesus Monkeys. Diabetes AS, 204-211. 

Clement S, Krause U, Desmedt F, Tanti J.F, Behrends J., Pesesse X., Sasaki T., Penninger J., Doherty M., Malaisse W., Dumont J.E., Le Marchand-Brustel Y., Emeux C., Hue L., and Schurmans S., 2001 The lipid phosphatase SHIP2 controls insulin sensitivity. 

Nagao, K., Inoue, N., Ujino, Y., Higa, K., Shirouchi, B., Wang, Y. M., and Yanagita, T. 2008. Effect of leptin infusion on insulin sensitivity and lipid metabolism in diet-induced lipodystrophy model mice. Lipids Health Dis., 7, 8. 

---