Document Detail

Differential effects of n-3 polyunsaturated fatty acids on metabolic control and vascular reactivity in the type 2 diabetic ob/ob mouse.
MedLine Citation:
PMID:  16979408     Owner:  NLM     Status:  MEDLINE    
Diets rich in monounsaturated fatty acids (MUFA) are recommended for individuals with type 2 diabetes mellitus (T2DM). The American Heart Association recommends increasing intakes of n-3 polyunsaturated fatty acids (PUFA) to reduce the risk of vascular disease in high-risk individuals; however, the long-term effects of these bioactive fatty acids on glucose metabolism in insulin resistance are controversial. The present studies were conducted to evaluate the effects of diets rich in both MUFA and alpha linolenic acid (C18:3n-3, ALA), eicosapentaenoic acid (C20:5n-3, EPA), or docosahexaenoic acid (C22:6n-3, DHA), on glycemic control and other parameters related to vascular health in a mouse model of T2DM and insulin resistance. Male ob/ob mice (n = 15 per treatment) were fed 1 of 4 lipid-modified formula diets (LFDs) for 4 weeks: (1) MUFA control, (2) ALA blend, (3) EPA blend, and (4) DHA blend. A portion of a MUFA-rich lipid blend in the control LFD was replaced with 11% to 14% energy as n-3 PUFA. After 4 weeks, plasma glucose response to a standard meal (1.5 g carbohydrate/kg body weight) and insulin challenge (2 U/kg body weight, IP) was assessed, and samples were collected for analysis of glucose, insulin, and lipids. Vascular reactivity of isolated aortic rings was assessed in an identical follow-up study. The results showed that insulin-resistant mice fed an LFD with EPA and/or DHA blends had significantly (P < .05) lower triglycerides and free fatty acids, but insulin sensitivity and fasting plasma glucose were not improved. However, mice fed with the ALA blend had significantly improved insulin sensitivity when compared to those fed with other LFD (P < .05). Animals fed an LFD with n-3 PUFA from marine or plant sources showed significantly improved vascular responses as compared with the MUFA-rich LFD (E(max), P < .05) and ob/ob reference mice consuming chow (E(max) and pEC(50), P < .05). In summary, long-term consumption of LFD with n-3 PUFAs improved blood lipids and vascular function in an animal model of insulin resistance and T2DM; however, only MUFA-rich LFD with ALA also improved both insulin sensitivity and glycemic responses. Further studies of MUFA-rich LFD with ALA with individuals who have T2DM are warranted.
Vikkie A Mustad; Stephen Demichele; Yung-Sheng Huang; Amanda Mika; Nathan Lubbers; Nathalie Berthiaume; Jim Polakowski; Brad Zinker
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  55     ISSN:  0026-0495     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-18     Completed Date:  2006-10-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1365-74     Citation Subset:  IM    
Healthy Living Research and Development, Ross Products Division, Abbott Laboratories, Columbus, OH 43215, USA.
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MeSH Terms
Area Under Curve
Blood Glucose / metabolism
Blood Vessels / drug effects*,  physiopathology*
Body Weight / physiology
Diabetes Mellitus, Type 2 / metabolism*,  physiopathology*
Dose-Response Relationship, Drug
Fatty Acids / analysis
Fatty Acids, Nonesterified / blood
Fatty Acids, Omega-3 / pharmacology*
Glucose Tolerance Test
Insulin / blood
Insulin Resistance
Mice, Obese
Phospholipids / blood
Structure-Activity Relationship
Triglycerides / blood
Reg. No./Substance:
0/Blood Glucose; 0/Fatty Acids; 0/Fatty Acids, Nonesterified; 0/Fatty Acids, Omega-3; 0/Phospholipids; 0/Triglycerides; 11061-68-0/Insulin

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