| Pulsatile changes in free fatty acids augment hepatic glucose production and preserves peripheral glucose homeostasis. | |
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MedLine Citation:
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PMID: 20424137 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recent studies in animal and human models have revealed that free fatty acid (FFA) release from adipose tissue is oscillatory. We have shown in our laboratory that these oscillations are controlled by the sympathetic nervous system (SNS). Although FFAs have been shown to directly stimulate glucose production [endogenous glucose production (EGP)] by the liver and to reduce peripheral glucose utilization, whether the specific pattern of FFA release affects glucose metabolism is unknown. The aim of this study was to examine the effects of pulsatile vs. constant infusion of FFA on glucose homeostasis in the canine model. Euglycemic clamps with basal insulin replacement (0.1 mU.kg(-1).min(-1) insulin) were performed in dogs (n = 8) during infusion of saline (SAL) or the medium-chain fatty acid octanoate, which was given by either pulsatile infusion (PUL: 10 mmol over 2 min every 10 min) or continuous infusion (C-INF: 1 mmol/min) designed to achieve equivalent total FFA mass. Endogenous lipolytic pulses were suppressed with the beta(3)-specific adrenergic receptor antagonist bupranolol. PUL infusion elicited a pulsatile pattern of FFA in circulation with average maximum pulse height of 0.82 +/- 0.04 mM, whereas C-INF FFA levels reached 0.47 +/- 0.03 mM (fasting levels) and were maintained throughout. Glucose uptake was not affected by PUL; however, C-INF significantly reduced glucose uptake compared with both SAL and PUL. Steady-state EGP increased by >90% from basal steady state during PUL but did not change during either SAL or C-INF. Thus, pulsatile FFA infusion led to an increase in EGP while preserving glucose disposal. These data suggest that the pattern of FFA may have a role in regulation of glucose homeostasis, which may have consequences in the obese or insulin-resistant state where the SNS is known to be altered. |
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Authors:
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Isabel R Hsu; Edward Zuniga; Richard N Bergman |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-04-27 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 299 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-14 Completed Date: 2010-07-14 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E131-6 Citation Subset: IM |
Affiliation:
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Keck School of Medicine, University of Southern California, 1333 San Pablo Street, Los Angeles, CA 90033, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antihypertensive Agents / pharmacology Biological Clocks / physiology Bupranolol / pharmacology Dogs Fatty Acids, Nonesterified / metabolism* Glucose / metabolism* Homeostasis Liver / metabolism* Male |
| Grant Support | |
ID/Acronym/Agency:
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DK-27619/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Fatty Acids, Nonesterified; 23284-25-5/Bupranolol; 50-99-7/Glucose |
| Comments/Corrections | |
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