| Inhibiting gluconeogenesis prevents fatty acid-induced increases in endogenous glucose production. | |
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MedLine Citation:
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PMID: 19417129 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glucose effectiveness, the ability of glucose per se to suppress endogenous glucose production (EGP), is lost in type 2 diabetes mellitus (T2DM). Free fatty acids (FFA) may contribute to this loss of glucose effectiveness in T2DM by increasing gluconeogenesis (GNG) and impairing the response to hyperglycemia. Thus, we first examined the effects of increasing plasma FFA levels for 3, 6, or 16 h on glucose effectiveness in nondiabetic subjects. Under fixed hormonal conditions, hyperglycemia suppressed EGP by 61% in nondiabetic subjects. Raising FFA levels with Liposyn infusion for > or =3 h reduced the normal suppressive effect of glucose by one-half. Second, we hypothesized that inhibiting GNG would prevent the negative impact of FFA on glucose effectiveness. Raising plasma FFA levels increased gluconeogenesis by approximately 52% during euglycemia and blunted the suppression of EGP by hyperglycemia. Infusion of ethanol rapidly inhibited GNG and doubled the suppression of EGP by hyperglycemia, thereby restoring glucose effectiveness. In conclusion, elevated FFA levels rapidly increased GNG and impaired hepatic glucose effectiveness in nondiabetic subjects. Inhibiting GNG could have therapeutic potential in restoring the regulation of glucose production in type 2 diabetes mellitus. |
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Authors:
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Sylvia Kehlenbrink; Julia Tonelli; Sudha Koppaka; Visvanathan Chandramouli; Meredith Hawkins; Preeti Kishore |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-05-05 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 297 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-26 Completed Date: 2009-08-10 Revised Date: 2010-09-27 |
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: E165-73 Citation Subset: IM |
Affiliation:
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Division of Endocrinology and Diabetes Research and Training Center, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Down-Regulation / drug effects Efficiency / drug effects Ethanol / pharmacology* Fatty Acids, Nonesterified / pharmacology* Female Gluconeogenesis / drug effects* Glucose / metabolism* Glucose Clamp Technique / methods Humans Liver / drug effects, metabolism Male Middle Aged Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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1-P01-AG-021654/AG/NIA NIH HHS; 1K23-RR-02335-01/RR/NCRR NIH HHS; 5-R01-DK-069861/DK/NIDDK NIH HHS; M01-RR-12248/RR/NCRR NIH HHS; P60-DK-20541/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids, Nonesterified; 50-99-7/Glucose; 64-17-5/Ethanol |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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