Genetics of insulin resistance英文文献.pdfVIP

Exp Clin Endocrinol Diabetes 107 (1999) 113-118 Experimental and Clinical Endocrinology Diabetes © 1999 Johann Ambrosius Barth Genetics of insulin resistance O. Pedersen Steno Diabetes Centre, Gentofte, Copenhagen, Denmark Key words: Insulin resistance, genetics, mutation, insulin receptor is associated with a significant (20-30%) impairment of insulin- substrate 1, phosphatidylinositol 3-kinase, glycogen-associated pro- stimulated P13-kinase activity, as well as reduced binding of IRS-i tein phosphatase-1 to the p85 regulatory subunit of P13-kinase. Genotype/phenotype studies stratified according to body mass index (BMI) indicate that Summary: Even among young, healthy individuals, there is more obese subjects who are heterozygous for the mutant allele have a than a 10-fold variation in insulin sensitivity; however, taken in 50°/ decrease in insulin sensitivity, compared with wild-type obese combination, all the known modifiers of insulin sensitivity - in- subjects. This suggests that there may be an interaction between cluding obesity and a variety of environmental factors - explain the mutant allele and obesity, such that, in the presence of obesity, less than one third of this variation. lt is possible that genetic fac- the mutant variant may aggravate the obesity-associated insulin re- tors could account for the bulk of the varianc