Posts Tagged ‘natural therapy for diabetes’

Omega-3 fatty acids attenuate constitutive and insulin-induced CD36 expression through a suppression of PPAR α/γ activity in microvascular endothelial cells.

Saturday, September 10th, 2011

Raffaele De Caterina, MD, PhD, Institute of Cardiology, “G. d’Annunzio” University – Chieti, C/o Ospedale SS. Annunziata, Via dei Vestini, 66013 Chieti, Italy, Tel: +39 0871 41512, Fax: +39 0871 553 461, E-mail: rdecater@unich.it.

Abstract

Microvascular dysfunction occurs in insulin resistance and/or hyperinsulinaemia. Enhanced uptake of free fatty acids (FFA) and oxidised low-density lipoproteins (oxLDL) may lead to oxidative stress and microvascular dysfunction interacting with CD36, a PPARα/γ-regulated scavenger receptor and long-chain FFA transporter. We investigated CD36 expression and CD36-mediated oxLDL uptake before and after insulin treatment in human dermal microvascular endothelial cells (HMVECs), ± different types of fatty acids (FA), including palmitic, oleic, linoleic, arachidonic, eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. Insulin (10⁻⁸ and 10⁻⁷ M) time-dependently increased DiI-oxLDL uptake and CD36 surface expression (by 30 ± 13%, p<0.05 vs. untreated control after 24 hours incubation), as assessed by ELISA and flow cytometry, an effect that was potentiated by the PI3-kinase inhibitor wortmannin and reverted by the ERK1/2 inhibitor PD98059 and the PPARα/γ antagonist GW9662. A ≥24 hour exposure to 50 μM DHA or EPA, but not other FA, blunted both the constitutive (by 23 ℜ∓ 3% and 29 ± 2%, respectively, p<0.05 for both) and insulin-induced CD36 expressions (by 45 ± 27 % and 12 ± 3 %, respectively, p<0.05 for both), along with insulin-induced uptake of DiI-oxLDL and the downregulation of phosphorylated endothelial nitric oxide synthase (P-eNOS). At gel shift assays, DHA reverted insulin-induced basal and oxLDL-stimulated transactivation of PPRE and DNA binding of PPARα/γ and NF-κB. In conclusion, omega-3 fatty acids blunt the increased CD36 expression and activity promoted by high concentrations of insulin. Such mechanisms may be the basis for the use of omega-3 fatty acids in diabetic microvasculopathy.

Omega 3 fish oil EPA Slows Progress of Atherosclerosis in Diabetic Patients

Tuesday, July 12th, 2011

EPA Slows Progress of Atherosclerosis in Diabetic Patients

People with type 2 diabetes are more likely to develop heart disease, circulatory problems and damaged organs than people without the condition. Impaired blood circulation, particularly in the small blood vessels, contributes to damaged eyes, kidneys and feet. Thus, in caring for diabetic patients, doctors pay close attention to blood circulation. To date, there are not many ways of improving the damaged blood vessels that develop in atherosclerosis and type 2 diabetes.

The fatty acids in fish oils, known as long-chain omega-3s, are known to improve blood vessel function in patients with heart disease. They relax the muscles in the blood vessel walls, reduce inflammation and lower blood clotting. These properties make them good candidates for improving blood vessel function in type 2 diabetics. Accordingly, a team of Japanese investigators examined the effect of consuming nearly 2 g/day of EPA, on the thickness of the carotid artery wall in diabetic patients. EPA is one of the major long-chain omega-3 fatty acids in fish oil. This dose is about the equivalent of 2 servings of salmon/day. Study participants consumed the omega-3 supplements for 2 years. Patients who were given standard medical treatment, but no supplements, were used for comparison.

At the end of the study, patients consuming EPA had a significant decrease of 4.7% in the thickness of their carotid wall compared with an increase of 2.4% in patients receiving standard care. Measurements of blood flow also improved in the EPA patients. There was a small increase in glycosylated hemoglobin, a sensitive measure of elevated blood glucose, in the EPA group and a decrease in the control patients. While this outcome was undesirable, such values in individual patients would call for aggressive patient management. This finding indicates that diabetic patients who consume large amounts of fish oil should be regularly monitored by their doctors for blood glucose control. With regular check-ups, diabetic patients can obtain the heart and circulatory system benefits of fish oil without compromising their diabetes status. Overall, this study adds to the growing evidence that long-chain omega-3 fatty acids may slow the progression of atherosclerosis in patients with type 2 diabetes or coronary artery disease.

Omega 3 fish oil may help activate anti-diabetic genes

Tuesday, March 8th, 2011

Fish oils may help to activate anti-diabetic genes

Polyunsaturated fatty acid fish oils may activate genes that regulate fat cell differentiation and glucose homeostasis, according to new research on mice.

The new study published in Journal of Nutritional Biochemistry suggests supplementation with omega3 fish oil activates the transcription factor PPARγ, increasing regulation of adipocytes and helps to maintain glucose homeostasis.

“We demonstrated that adipogenic genes and glucose metabolism genes were elevated in PPARγ transgenic mice when fed fish oil. This transgenic mouse model provided direct evidence to demonstrate omega 3 , especially EPA  regulate glucose homeostasis through interaction with PPARγ,” wrote the researchers, led by Dr Yu-Hsiang Yu from the National Taiwan University

Vital roles

Peroxisome-proliferator-activated receptor γ (PPARγ) is considered an important transcription factor in regulating fat cell (adipocyte) differentiation, and is also known to play a vital role in maintaining glucose homeostasis. The transcription factor is a target for many anti-diabetic drugs as activation promotes glucose dispersal.

Activation of PPARγ occurs through the binding of specific ligand molecules; however, polyunsaturated fatty acids such as arachidonic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are also known to have a high binding affinity for PPARγ.

Previous studies suggest that polyunsaturated fatty acids (PUFA) and their metabolites are able to regulate PPARγ activity, demonstrating that DHA treatment increases PPARγ-responsive gene expression in a cell model.

However, most research demonstrating PPARγ activity uses in vitro cell models and there is currently no direct evidence available to demonstrate that polyunsaturated fatty acids are able to activate PPARγ in vivo.

The authors said the current experiment was designed to determine the potential for PUFA, particularly EPA and DHA, to activate the function of PPARγ in vivo.

Wild-type and transgenic mice – with over expressed PPARγ –were supplemented with either fish oil or PPARγ ligands (rosiglitazone) for four months to investigate whether fish oils have similar effects to true PPARγ ligands in vivo.

Results

Dietary rosiglitazone fed mice had a significantly lower feed intake, but had no significant effect on body weight or fat pad weigh, whereas fish oil supplementation did not significantly decrease feed intake, but significantly decreased body and fat pad weight, found the researchers.

Dr. Yu and colleagues reported that adipogenic genes (LPL, FAT, SREBP-1c and FAS) were markedly up-regulated by rosiglitazone supplementation. Fish oil supplementation increased LPL and FAT, but not SREBP-1c or FAS; however, stained muscle sections indicated no lipid accumulation in skeletal muscle.

Researchers noted that transgenic mice fed a fish oil supplementation had increased expression of adipogenic and glucose uptake genes, leading to reduced plasma glucose concentration.

Natural regulator

The authors suggested that polyunsaturated fatty acids, particularly EPA and DHA, may serve as a natural regulator of glucose uptake in vivo, stating that such effects are mainly mediated through PPARγ activation.

“Our data demonstrated that the PPARγ-regulated glucose metabolism genes, GLUT-4 and ADN were dramatically increased in skeletal muscle of PPARγ transgenic mice when fed rosiglitazone or fish oil, suggesting activation … by either ligand,” concluded the authors.

Source: Journal of Nutritional Biochemistry

“The function of porcine PPARγ and dietary fish oil effect on the expression of lipid and glucose metabolism related genes”

Omega-3-rich supplements may improve blood lipid levels of people with metabolic syndrome

Tuesday, March 8th, 2011

Omega-3-rich supplements may improve blood lipid levels of people with metabolic syndrome, reducing the risks of developing serious health problems, says a new study.

The research, published in The Journal of Nutrition, suggests that the effects of metabolic syndrome– a major risk factor for insulin resistance and diabetes – can be reduced through the addition of omega 3 fatty acids in low-fat, high-complex carbohydrate diets.

“Fish oil supplements correct many metabolic alterations associated with insulin resistance, including reduced postprandial plasma triglyceride concentration” stated the researchers, led by Jose Lopez-Miranda from the University of Cordoba, Spain.

Risk factors

Metabolic syndrome is the name given to a group of risk factors that frequently include obesity, hypertension, high levels of blood lipids, and high blood sugars.

The condition is a common precursor to type II diabetes, and is also strongly associated with increased risk of major health problems such as heart disease and stroke.

The causes of metabolic syndrome are unknown, although they are thought to involve both genetic and environmental factors – including poor diet.

One way to increase the overall health – and reduce the risks – of people with metabolic syndrome, has been to eat a diet low in saturated fat and high in complex carbohydrates. However, previous research has suggested that this diet does not help to reduce high levels of blood lipids – with some studies observing such a diet could even be raising blood lipid levels.

Positive effects

The new study looked into the effects of four different diet combinations on blood lipid metabolism, in 117 patients with metabolic syndrome.

In accordance with previous suggestions, the researchers found that a low-fat, high-complex carbohydrate diet had “several detrimental effects”, including significantly increasing total triglyceride levels, and triglyceride rich lipoprotein cholesterol levels.

In contrast, intake of the same diet supplemented with omega-3 was found to have no effects on blood lipid levels, with researchers observing that a diet rich in monounsaturated fats, or a low-fat diet rich in complex carbohydrates and omega-3 fatty acids, resulted in lower circulating blood lipid levels than a diet rich in high saturated fats or a diet low in fats and high in complex carbohydrates.

The data from the study suggest a place for higher omega-3 intake in people with metabolic syndrome, and supports previous research that suggests monounsaturated fatty acids can have a positive effect on blood lipid levels.

“The long-term effect of the low-fat, high-complex carbohydrate diet, pre vs. post intervention phases, showed several beneficial effects of long chain omega-3 PUFA supplementation,” stated the researchers.

“Our data suggest that long-term intake of an isocaloric, low-fat, high-carbohydrate diet supplemented with long chain omega-3 … have beneficial effects on postprandial lipoprotein response in patients with metabolic syndrome,”

Source: The Journal of Nutrition
Published online ahead of print, doi:10.3945/jn.109.120816
“A Low-Fat, High-Complex Carbohydrate Diet Supplemented with Long-Chain (n-3) Fatty Acids Alters the Postprandial Lipoprotein Profile in Patients with Metabolic Syndrome”
Authors: Y. Jimenez-Gomez, C. Marin, P. Perez-Martinez, et al

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