Effects of pioglitazone on intramyocellular fat metabolism in patients with type 2 diabetes mellitus

Mandeep Bajaj, Rais Baig, Swangjit Suraamornkul, Lou Jean Hardies, Dawn K. Coletta, Gary W. Cline, Adriana Monroy, Shailja Koul, Apiradee Sriwijitkamol, Nicolas Musi, Gerald I. Shulman, Ralph A. DeFronzo

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53 Scopus citations

Abstract

Context: Lipotoxicity (increased tissue fat content) has been implicated in the development of muscle insulin resistance and type 2 diabetes mellitus (T2DM). Objective: The aim was to study the effect of pioglitazone on intramyocellular fat metabolism. Research Design: Twenty-four T2DM subjects (glycosylated hemoglobin = 8.3 ± 0.4%) participated in three similar study protocols before and after 4 months of 45 mg/d pioglitazone treatment: 1) 3-h euglycemic insulin (80 mU/m2 · min) clamp with measurement of intramyocellular fat with proton nuclear magnetic resonance; 2) vastus lateralis muscle biopsy for measurement of LCFACoAs 60 min before start of the insulin clamp; and 3) muscle biopsy for measurement of diacylglycerol 60 min before start of the insulin clamp. Results: In all three protocols, pioglitazone similarly reduced (all P < 0.05) the glycosylated hemoglobin (Δ = 0.8-1.2%), fasting plasma glucose (39-76 mg/dl), fasting free fatty acid (132-236 μmol/liter), and increased insulin-stimulated glucose disposal (by 25-56%). Intramyocellular fat (protocol I) declined from 1.5 to 0.9% (P < 0.05) and correlated with the increase in glucose disposal rate (r = 0.65; P < 0.05). Long chain-fatty acyl-coenzyme A decreased from 12.5 to 8.1 nmol/g (P < 0.05) and correlated with the increase in disposal rate (r = 0.76; P < 0.05). Pioglitazone therapy had no effect on muscle diacylglycerol content. Conclusions: Pioglitazone improves insulin resistance in T2DM in association with mobilization of fat and toxic lipid metabolites out of muscle.

Original languageEnglish (US)
Pages (from-to)1916-1923
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume95
Issue number4
DOIs
StatePublished - Apr 2010

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Bajaj, M., Baig, R., Suraamornkul, S., Hardies, L. J., Coletta, D. K., Cline, G. W., Monroy, A., Koul, S., Sriwijitkamol, A., Musi, N., Shulman, G. I., & DeFronzo, R. A. (2010). Effects of pioglitazone on intramyocellular fat metabolism in patients with type 2 diabetes mellitus. Journal of Clinical Endocrinology and Metabolism, 95(4), 1916-1923. https://doi.org/10.1210/jc.2009-0911