Adipose tissue, hepatic, and skeletal muscle insulin sensitivity in extremely obese subjects with acanthosis nigricans

Dominic N. Reeds, Charles A. Stuart, Obed Perez, Samuel Klein

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

We evaluated insulin action in skeletal muscle (glucose disposal), liver (glucose production), and adipose tissue (lipolysis) in 5 extremely obese women with acanthosis nigricans (AN), who had normal oral glucose tolerance, and 5 healthy lean subjects, by using a 5-stage pancreatic clamp and stable isotopically labeled tracer infusion. Basal plasma insulin concentration was much greater in obese subjects with AN than lean subjects (54.8 ± 4.5 vs 8.0 ± 1.3 μU/mL, P < .001), but basal glucose and free fatty acid concentrations were similar in both groups. During stage 1 of the clamp, glucose rate of appearance (Ra) (2.6 ± 0.3 vs 3.7 ± 0.3 μmol · kg FFM-1 · min-1, P = .02) and palmitate Ra (2.4 ± 0.6 vs 7.0 ± 1.5 μmol · kg FFM-1 · min-1, P < .05) were greater in obese subjects with AN than lean subjects despite slightly greater plasma insulin concentration in subjects with AN (3.0 ± 0.7 vs 1.1 ± 0.4 μU/mL, P < .05). The area under the curve for palmitate Ra (1867 ± 501 vs 663 ± 75 μmol · kg FFM-1 · 600 min-1, P = .03) and glucose Ra (1920 ± 374 vs 1032 ± 88 μmol · kg FFM-1 · 600 min-1, P = .02) during the entire clamp procedure was greater in subjects with AN than lean subjects. During intermediate insulin conditions (plasma insulin, ~35 μU/mL), palmitate Ra was 5-fold greater in subjects with AN than in lean subjects (2.6 ± 1.1 vs 0.5 ± 0.2 μmol · kg FFM-1 · min-1, P = .05). Maximal glucose disposal was markedly lower in obese subjects with AN than in lean subjects (13.0 ± 0.8 vs 23.4 ± 1.8 mg · kg FFM-1 · min-1, P = .01) despite greater peak plasma insulin concentration (1842 ± 254 vs 598 ± 38 μU/mL, P < .05). These data demonstrate obese young adults with AN have marked insulin resistance in multiple tissues. However, marked insulin hypersecretion can compensate for impaired insulin action, resulting in normal glucose and fatty acid metabolism during basal conditions.

Original languageEnglish
Pages (from-to)1658-1663
Number of pages6
JournalMetabolism: clinical and experimental
Volume55
Issue number12
DOIs
StatePublished - Dec 1 2006

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