Insulin resistance contributes to the pathogenesis of several disease states including obesity and noninsulin-dependent diabetes mellitus (NIDDM). We have investigated the insulin receptor gene in patients with genetic forms of insulin resistance to gain insight into biochemical defects that give rise to disease. Five classes of mutations have been identified: 1) Impaired receptor biosynthesis, due to either decreased levels of insulin receptor mRNA and/or premature chain termination mutations; 2) Impaired transport of receptors to the plasma membrane, due to missense mutations in the extracellular domain of the receptor; 3) Decreased affinity of insulin binding; 4) Decreased activity of the insulin receptor tyrosine kinase, and 5) Accelerated receptor degradation associated with resistance to the effect of acid pH to dissociate insulin from its receptor within the endosome. Studies are presently underway to estimate the prevalence of mutations in the insulin receptor gene in order to determine whether mutations in this gene contribute to the pathogenesis of the common form of noninsulin- dependent diabetes mellitus.
| Javor, Edward D; Moran, Stephanie Ann; Young, Janice Ryan et al. (2004) Proteinuric nephropathy in acquired and congenital generalized lipodystrophy: baseline characteristics and course during recombinant leptin therapy. J Clin Endocrinol Metab 89:3199-207 |
| Musso, Carla; Cochran, Elaine; Moran, Stephanie Ann et al. (2004) Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): a 30-year prospective. Medicine (Baltimore) 83:209-22 |
| Moran, Stephanie Ann; Patten, Nicole; Young, Janice Ryan et al. (2004) Changes in body composition in patients with severe lipodystrophy after leptin replacement therapy. Metabolism 53:513-9 |
| Cochran, Elaine; Young, Janice Ryan; Sebring, Nancy et al. (2004) Efficacy of recombinant methionyl human leptin therapy for the extreme insulin resistance of the Rabson-Mendenhall syndrome. J Clin Endocrinol Metab 89:1548-54 |
| Agarwal, Anil K; Simha, Vinaya; Oral, Elif Arioglu et al. (2003) Phenotypic and genetic heterogeneity in congenital generalized lipodystrophy. J Clin Endocrinol Metab 88:4840-7 |
| Gorden, Phillip; Gavrilova, Oksana (2003) The clinical uses of leptin. Curr Opin Pharmacol 3:655-9 |
| Petersen, Kitt Falk; Oral, Elif Arioglu; Dufour, Sylvie et al. (2002) Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest 109:1345-50 |
| Bolan, Charles; Oral, Elif Arioglu; Gorden, Phillip et al. (2002) Intensive, long-term plasma exchange therapy for severe hypertriglyceridemia in acquired generalized lipoatrophy. J Clin Endocrinol Metab 87:380-4 |
| Oral, Elif Arioglu; Simha, Vinaya; Ruiz, Elaine et al. (2002) Leptin-replacement therapy for lipodystrophy. N Engl J Med 346:570-8 |
| Oral, Elif Arioglu; Ruiz, Elaine; Andewelt, Alexa et al. (2002) Effect of leptin replacement on pituitary hormone regulation in patients with severe lipodystrophy. J Clin Endocrinol Metab 87:3110-7 |
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