ECE2006 Poster Presentations Diabetes, metabolism and cardiovascular (174 abstracts)
Insulin receptoropathies are distinguished from other syndromes of severe insulin resistance by elevated plasma adiponectin levels
RK Semple 1 , MA Soos 1 , CM Mitchell 3 , JC Wilson 1 , J Luan 2 , EK Cochran 4 , NJ Wareham 2 , P Gorden 4 , VKK Chatterjee 3 & S O’Rahilly 1
1Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom; 2Medical Research Council Epidemiology Unit, Elsie Widdowson Laboratories, Cambridge, United Kingdom; 3Department of Medicine, University of Cambridge, Cambridge, United Kingdom; 4Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, United States.
Leptin and adiponectin are cytokine-like hormones secreted by white adipose tissue. Plasma leptin correlates closely with total body fat mass, and its secretion is positively regulated by insulin in vivo and in vitro. Hypoleptinaemia is a key centrally-mediated orexigenic stimulus. Plasma adiponectin, in contrast, correlates negatively with whole body fat mass and insulin resistance in adults, and its expression is regulated negatively by insulin in vivo and in vitro. We have now determined plasma leptin and adiponectin in subjects with severe insulin resistance due to insulin receptor or AKT2 loss-of-function mutations, in those with syndromes of lipodystrophy due to mutations in PPARgamma, Lamin A/C, AGPAT2 or BSCL2, and in those with severe insulin resistance of undefined molecular origin. Subjects with insulin receptoropathies, despite having the most severe degree of insulin resistance, had elevated plasma adiponectin (median 24.4 mg/l; range 6.6–27.6), while all other subjects, including those with defective AKT2 function, had low adiponectin levels in keeping with previous observations (median 2.0 mg/l; range 0.12–11.2). Plasma leptin in all but one subject with defective insulin receptors was low or undetectable (median 0.5 ng/ml; range 0–16), closer to the levels in total lipodystrophy (median 0.1 ng/ml; range 0–0.4) than in partial lipodystrophy (median 5.6 ng/ml; range 0.2–12.4). These finding suggests that high plasma adiponectin with low leptin may be used as a biochemical discriminator of those severely insulin resistant subjects who harbor insulin receptor mutations, and we speculate that this reflects impaired adipocyte maturation in these subjects.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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