| Elevated circulating free fatty acids levels causing pancreatic islet cell dysfunction through oxidative stress. | |
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MedLine Citation:
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PMID: 19915385 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Elevated plasma free fatty acids (FFA) concentration is predictive of the conversion from normal glucose tolerance and impaired glucose tolerance to diabetes. AIMS: To evaluate the effects of prolonged exposure to FFA on basal and glucose-stimulated insulin secretion (GSIS) of pancreatic beta-cell, and to investigate the role of oxidative stress in FFA-induced decrease in beta-cell function. METHODS: Rats were assigned to 3 groups and underwent 96-h infusions of normal saline (NS), intralipid plus heparin (IH), or intralipid plus heparin and N-acetylcysteine (IH+NAC). The plasma insulin, malonyldialdehyde (MDA), reduced glutathione (GSH), and oxidized glutathione (GSSG) were measured. In vivo intravenous glucose tolerance test (IVGTT) and ex vivo isolated pancreatic tissues perfusion were performed. RESULTS: In IH group GSIS both in IVGTT and perifused pancreatic tissues were impaired (p<0.05), the GSH/GSSG ratio was declined and MDA levels increased (p<0.05), the volume density score of nuclear factor kappaB and inducible nitric oxide synthase in pancreatic islets were increased compared to the NS group (p<0.01). In IH+NAC group, NAC intervention partly restored the GSH/GSSG ratio and MDA level, and improved FFA induced GSIS impairment. CONCLUSION: Elevated circulating FFA levels may contribute to causing the abnormalities of pancreatic islet cell function through active oxidative stress and oxidative stress-sensitive signaling pathway, which may play a key role in the development of impaired insulin secretion seen in obese Type 2 diabetes. |
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Authors:
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X Zhang; Y Bao; L Ke; Y Yu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-12 |
Journal Detail:
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Title: Journal of endocrinological investigation Volume: 33 ISSN: 1720-8386 ISO Abbreviation: J. Endocrinol. Invest. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-07-14 Completed Date: 2010-10-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7806594 Medline TA: J Endocrinol Invest Country: Italy |
Other Details:
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Languages: eng Pagination: 388-94 Citation Subset: IM |
Affiliation:
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Division of Endocrinology and Metabolism, Sichuan University, West China Hospital, Cheng Du, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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pharmacology Animals Fat Emulsions, Intravenous / pharmacology Fatty Acids, Nonesterified / adverse effects, blood* Glucose / metabolism Glucose Tolerance Test Glutathione / metabolism Insulin / secretion* Islets of Langerhans / drug effects*, secretion Male Malondialdehyde / metabolism Oxidative Stress / drug effects* Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Fat Emulsions, Intravenous; 0/Fatty Acids, Nonesterified; 11061-68-0/Insulin; 50-99-7/Glucose; 542-78-9/Malondialdehyde; 616-91-1/Acetylcysteine; 70-18-8/Glutathione |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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