Differential effects of n-3 polyunsaturated fatty acids on metabolic control and vascular reactivity in the type 2 diabetic ob/ob mouse.
ABSTRACT 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.
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ABSTRACT: Purpose: Targeted inhibition of Müller cell (MC)-produced VEGF or broad inhibition of VEGF with an intravitreal anti-VEGF antibody reduces intravitreal neovascularization in a rat model of ROP. In this study, we compared the effects of these two approaches on retinal vascular development and capillary density in the inner and deep plexi in the rat ROP model. Methods: In the rat model of ROP, pups received one-microliter of 1) subretinal lentivector-driven shRNA to knockdown MC-VEGFA (VEGFA.shRNA) or control luciferase shRNA, or 2) intravitreal anti-VEGF antibody (anti-VEGF) or control IgG. Analyses of lectin-stained flat mounts at p18 included: vascular/total retinal areas (retinal vascular coverage) and pixels of fluorescence/total retinal area (capillary density) of the inner and deep plexi determined with the Syncroscan microscope, and angles between cleavage planes of mitotic vascular figures labeled with anti-phosphohistone H3 and vessel length. Results: Retinal vascular coverage and density increased in both plexi between p8 and p18 in room air (RA) pups. Compared to RA, p18 ROP pups had reduced vascular coverage and density of both plexi. Compared to respective controls, VEGFA.shRNA treatment significantly increased vascular density in the deep plexus, whereas anti-VEGF reduced vascular density in the inner and deep plexi. VEGFA.shRNA caused more cleavage angles predicting vessel elongation and fewer mitotic figures, whereas anti-VEGF treatment led to patterns of pathologic angiogenesis. Conclusions: Targeted treatment with lentivector-driven VEGFA.shRNA permitted physiologic vascularization of the vascular plexi and restored normal orientation of dividing vascular cells, suggesting that regulation of VEGF signaling by targeted treatment may be beneficial.Investigative ophthalmology & visual science 01/2014; · 3.43 Impact Factor
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ABSTRACT: Eicosapentaenoic acid-enriched phosphatidylcholine was isolated from the sea cucumber Cucumaria frondosa (Cucumaria-PC) and its effects on streptozotocin (STZ)-induced hyperglycemic rats were investigated. Male Sprague-Dawley rats were randomly divided into normal control, model control (STZ), low- and high-dose Cucumaria-PC groups (STZ + Cucumaria-PC at 25 and 75 mg/Kg·b·wt, intragastrically, respectively). Blood glucose, insulin, glycogen in liver and gastrocnemius were determined over 60 days. Insulin signaling in the rats' gastrocnemius was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. The results showed that Cucumaria-PC significantly decreased blood glucose level, increased insulin secretion and glycogen synthesis in diabetic rats. RT-PCR analysis revealed that Cucumaria-PC significantly promoted the expressions of glycometabolism-related genes of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI3K), protein kinase B (PKB), and glucose transporter 4 (GLUT4) in gastrocnemius. Western blotting assay demonstrated that Cucumaria-PC remarkably enhanced the proteins abundance of IR-β, PI3K, PKB, GLUT4, as well as phosphorylation of Tyr-IR-β, p85-PI3K, Ser473-PKB (P < 0.05 and P < 0.01). These findings suggested that Cucumaria-PC exhibited significant anti-hyperglycemic activities through up-regulating PI3K/PKB signal pathway mediated by insulin. Nutritional supplementation with Cucumaria-PC, if validated for human studies, may offer an adjunctive therapy for diabetes mellitus.Journal of Bioscience and Bioengineering 10/2013; · 1.74 Impact Factor
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ABSTRACT: Objective: This is an Asian study, which was designed to examine the correlations between biochemical data and food composition of diabetic patients in Taiwan. Methods: One hundred and seventy Taiwanese diabetic patients were enrolled. The correlations between biochemical data and diet composition (from 24-hour recall of intake food) of these patients were explored (Spearman correlation, p < 0.05). Diet components were also correlated with each other to show diet characteristics of diabetic patients in Taiwan. Linear regression was also performed for the significantly correlated groups to estimate possible impacts from diet composition to biochemical data. Results: Postprandial serum glucose level was negatively correlated with fat percentage of diet, intake amount of polyunsaturated fatty acid and fiber diet composition. Hemoglobin A1c was negatively correlated with fat diet, polyunsaturated fatty acid and vegetable diet. Fat composition, calorie percentage accounted by polyunsaturated fatty acid and monounsaturated fatty acid in diet seemed to be negatively correlated with sugar percentage of diet and positively correlated with vegetable and fiber composition of diet. Linear regression showed that intake amount of polyunsaturated fatty acid, calorie percentage accounted by polyunsaturated fatty acid, fat percentage of diet, vegetable composition of diet would predict lower hemoglobin A1c and postprandial blood sugar. Besides, higher percentage of fat diet composition could predict higher percentage of vegetable diet composition in Taiwanese diabetic patients. Conclusion: Fat diet might not elevate serum glucose. Vegetable diet and polyunsaturated fatty acid diet composition might be correlated with better sugar control in Taiwanese diabetic patients.International journal of medical sciences 01/2014; 11(5):515-21. · 2.07 Impact Factor