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Free fatty acid-induced peripheral insulin resistance augments splanchnic glucose uptake in healthy humans

Free fatty acid-induced peripheral insulin resistance augments splanchnic glucose uptake in... Abstract To investigate the effect of elevated plasma free fatty acid (FFA) concentrations on splanchnic glucose uptake (SGU), we measured SGU in nine healthy subjects (age, 44 ± 4 yr; body mass index, 27.4 ± 1.2 kg/m 2 ; fasting plasma glucose, 5.2 ± 0.1 mmol/l) during an Intralipid-heparin (LIP) infusion and during a saline (Sal) infusion. SGU was estimated by the oral glucose load (OGL)-insulin clamp method: subjects received a 7-h euglycemic insulin (100 mU · m −2 · min −1 ) clamp, and a 75-g OGL was ingested 3 h after the insulin clamp was started. After glucose ingestion, the steady-state glucose infusion rate (GIR) during the insulin clamp was decreased to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in GIR during the period after glucose ingestion from the ingested glucose load. 3- 3 Hglucose was infused during the initial 3 h of the insulin clamp to determine rates of endogenous glucose production (EGP) and glucose disappearance (R d ). During the 3-h euglycemic insulin clamp before glucose ingestion, R d was decreased (8.8 ± 0.5 vs. 7.6 ± 0.5 mg · kg −1 · min −1 , P < 0.01), and suppression of EGP was impaired (0.2 ± 0.04 vs. 0.07 ± 0.03 mg · kg −1 · min −1 , P < 0.01). During the 4-h period after glucose ingestion, SGU was significantly increased during the LIP vs. Sal infusion study (30 ± 2 vs. 20 ± 2%, P < 0.005). In conclusion, an elevation in plasma FFA concentration impairs whole body glucose R d and insulin-mediated suppression of EGP in healthy subjects but augments SGU. liver oral glucose skeletal muscle Footnotes Address for reprint requests and other correspondence: M. Bajaj, Diabetes Division, Dept. of Medicine, Univ. of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78284--7886 (E-mail: mandeepbajaj@hotmail.com ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. April 9, 2002;10.1152/ajpendo.00329.2001 Copyright © 2002 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Endocrinology and Metabolism The American Physiological Society

Free fatty acid-induced peripheral insulin resistance augments splanchnic glucose uptake in healthy humans

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References (43)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1849
eISSN
1522-1555
DOI
10.1152/ajpendo.00329.2001
pmid
12110541
Publisher site
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Abstract

Abstract To investigate the effect of elevated plasma free fatty acid (FFA) concentrations on splanchnic glucose uptake (SGU), we measured SGU in nine healthy subjects (age, 44 ± 4 yr; body mass index, 27.4 ± 1.2 kg/m 2 ; fasting plasma glucose, 5.2 ± 0.1 mmol/l) during an Intralipid-heparin (LIP) infusion and during a saline (Sal) infusion. SGU was estimated by the oral glucose load (OGL)-insulin clamp method: subjects received a 7-h euglycemic insulin (100 mU · m −2 · min −1 ) clamp, and a 75-g OGL was ingested 3 h after the insulin clamp was started. After glucose ingestion, the steady-state glucose infusion rate (GIR) during the insulin clamp was decreased to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in GIR during the period after glucose ingestion from the ingested glucose load. 3- 3 Hglucose was infused during the initial 3 h of the insulin clamp to determine rates of endogenous glucose production (EGP) and glucose disappearance (R d ). During the 3-h euglycemic insulin clamp before glucose ingestion, R d was decreased (8.8 ± 0.5 vs. 7.6 ± 0.5 mg · kg −1 · min −1 , P < 0.01), and suppression of EGP was impaired (0.2 ± 0.04 vs. 0.07 ± 0.03 mg · kg −1 · min −1 , P < 0.01). During the 4-h period after glucose ingestion, SGU was significantly increased during the LIP vs. Sal infusion study (30 ± 2 vs. 20 ± 2%, P < 0.005). In conclusion, an elevation in plasma FFA concentration impairs whole body glucose R d and insulin-mediated suppression of EGP in healthy subjects but augments SGU. liver oral glucose skeletal muscle Footnotes Address for reprint requests and other correspondence: M. Bajaj, Diabetes Division, Dept. of Medicine, Univ. of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78284--7886 (E-mail: mandeepbajaj@hotmail.com ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. April 9, 2002;10.1152/ajpendo.00329.2001 Copyright © 2002 the American Physiological Society

Journal

AJP - Endocrinology and Metabolism – The American Physiological Society

Published: Aug 1, 2002

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