Elevated free fatty acids impair glucose metabolism in women: Decreased stimulation of muscle glucose uptake and suppression of splanchnic glucose production during combined hyperinsulinemia and hyperglycemia

Pankaj Shah, Adrian Vella, Ananda Basu, Rita Basu, Aron Adkins, W. Frederick Schwenk, C. Michael Johnson, K. Sreekumaran Nair, Michael D. Jensen, Robert A. Rizza

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

The present study sought to determine whether elevated plasma free fatty acids (FFAs) alter the splanchnic and muscle glucose metabolism in women. To do so, FFAs were increased in seven women by an 8-h Intralipid/heparin (IL/hep) infusion, and the results were compared with those observed in nine women who were infused with glycerol alone. Glucose was clamped at ∼8.3 mmol/l and insulin was increased to ∼300 pmol/l to stimulate both muscle and hepatic glucose uptake. Insulin secretion was inhibited with somatostatin. Leg and splanchnic glucose metabolism were assessed using a combined catheter and tracer dilution approach. The glucose infusion rates required to maintain target plasma glucose concentrations were lower (P < 0.01) during IL/hep than glycerol infusion (30.8 ± 2.6 vs. 65.0 ± 7.9 μmol · kg-1 · min-1). Whole-body glucose disappearance (37.0 ± 2.2 vs. 70.9 ± 8.7 μmol · kg-1 · min-1; P < 0.001) and leg glucose uptake (24.3 ± 4.2 vs. 59.6 ± 10.0 μmol · kg fat-free mass of the leg-1 · min-1; P < 0.02) were also lower, whereas splanchnic glucose production (8.2 ± 0.8 vs. 4.3 ± 0.7 μmol · kg-1 · min-1; P < 0.01) was higher during IL/hep than glycerol infusion. We conclude that in the presence of combined hyperinsulinemia and hyperglycemia, elevated FFAs impair glucose metabolism in women by inhibiting whole-body glucose disposal, muscle glucose uptake, and suppression of splanchnic glucose production.

Original languageEnglish (US)
Pages (from-to)38-42
Number of pages5
JournalDiabetes
Volume52
Issue number1
DOIs
StatePublished - Jan 1 2003

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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