| Combination therapy with nateglinide and vildagliptin improves postprandial metabolic derangements in Zucker fatty rats. | |
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MedLine Citation:
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PMID: 20625970 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Postprandial metabolic derangements are one of the risk factors of cardiovascular disease in humans. Insulin resistance and/or impaired early-phase insulin secretion are major determinants of postprandial metabolic derangements. In this study, we investigated the potential utility of combination therapy with vildagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor and nateglinide, a rapid-onset/short-duration insulinotropic agent, for the treatment of postprandial metabolic derangements in Zucker Fatty (ZF) rats, an animal model of obesity with insulin resistance. ZF rats fed twice daily with or without high fat diet (HFD) were given vehicle, 50 mg/kg of nateglinide, 10 mg/kg of vildagliptin, or both for 6 weeks. Combination therapy with nateglinide and vildagliptin for 2 weeks ameliorated postprandial hyperglycemia, hypertriglyceridemia, and elevation of free fatty acid in ZF rats fed with HFD. 6-week treatment with nateglinide and vildagliptin not only increased hepatic levels of phosphorylated forkhead box protein 1A (FOXO1A), but also reduced triglyceride contents in the liver. Combination therapy also prevented the loss of pancreatic islet mass in ZF rats fed with HFD. These observations demonstrate that combination therapy with nateglinide and vildagliptin may improve postprandial metabolic derangements probably by ameliorating early phase of insulin secretion and hepatic insulin resistance, respectively, in ZF rats fed with HFD. Since combination therapy with nateglinide and vildagliptin restored the decrease in pancreatic beta cell mass, our present findings suggest that combination therapy could be a promising therapeutic strategy for postprandial dysmetabolism associated with obese and insulin resistance. |
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Authors:
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K Miura; Y Kitahara; S Yamagishi |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-12 |
Journal Detail:
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Title: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme Volume: 42 ISSN: 1439-4286 ISO Abbreviation: Horm. Metab. Res. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-03 Completed Date: 2010-12-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0177722 Medline TA: Horm Metab Res Country: Germany |
Other Details:
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Languages: eng Pagination: 731-5 Citation Subset: IM |
Affiliation:
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Pharmaceutical Research Laboratories, Ajinomoto, Kawasaki, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adamantane
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analogs & derivatives*,
pharmacology,
therapeutic use Animals Blood Glucose / drug effects, metabolism Cyclohexanes / pharmacology, therapeutic use* Drug Therapy, Combination Fatty Acids / blood Forkhead Transcription Factors / metabolism Hypoglycemic Agents / pharmacology, therapeutic use* Insulin / blood Insulin-Secreting Cells / drug effects, metabolism, pathology Liver / drug effects, metabolism, pathology Male Metabolic Diseases / blood, drug therapy*, physiopathology* Nitriles / pharmacology, therapeutic use* Organ Size / drug effects Phenylalanine / analogs & derivatives*, pharmacology, therapeutic use Phosphorylation / drug effects Postprandial Period / drug effects, physiology* Pyrrolidines / pharmacology, therapeutic use* Rats Rats, Zucker Triglycerides / blood |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Cyclohexanes; 0/Fatty Acids; 0/Forkhead Transcription Factors; 0/Foxo1a protein, rat; 0/Hypoglycemic Agents; 0/Nitriles; 0/Pyrrolidines; 0/Triglycerides; 0/vildagliptin; 105816-04-4/nateglinide; 11061-68-0/Insulin; 281-23-2/Adamantane; 63-91-2/Phenylalanine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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