Danielle M. Stringer

Dietary milled flaxseed and flaxseed oil improve N-3 fatty acid status and do not affect glycemic control in individuals with well-controlled type 2 diabetes.

Objective: To determine the effects of dietary consumption of milled flaxseed or flaxseed oil on glycemic control, n-3 fatty acid status, anthropometrics, and adipokines in individuals with type 2 diabetes. Design: Thirty-four participants were randomized into a parallel, controlled trial. Subjects: The participants were adults with type 2 diabetes (age 52.4 ± 1.5 years, body mass index 32.4 ± 1.0 kg/m2, n  =  17 men and 17 women). Interventions: Participants consumed a selection of bakery products containing no flax (control group [CTL], n  =  9), milled flaxseed (FXS, n  =  13; 32 g/d), or flaxseed oil (FXO, n  =  12; 13 g/d) daily for 12 weeks. The FXS and FXO groups received equivalent amounts of alpha-linolenic acid (ALA; 7.4 g/day). Measures of Outcome: The primary outcome measures were fasting plasma hemoglobin A1c, glucose, insulin, and phospholipid fatty acid composition. The secondary outcome measures were fasting circulating leptin and adiponectin, as well as body weight, body mass index, and waist circumference. Dietary intake assessment and calculations for homeostasis model assessment for insulin resistance and quantified insulin sensitivity check were also completed. Results: The FXS and FXO groups had increases in plasma phospholipid n-3 fatty acids (ALA, eicosapentaenoic acid [EPA], or decosapentaenoic acid [DPA], but not docosahexaenoic acid), and the FXO group had more EPA and DPA in plasma phospholipids compared to the FXS group. All groups had similar caloric intakes; however, the CTL group experienced a 4% weight gain compared to baseline (p < 0.05), while both flax groups had constant body weights during the study period. All other parameters, including glycemic control, were unchanged by dietary treatment. Conclusions: Milled FXS and FXO intake does not affect glycemic control in adults with well-controlled type 2 diabetes. Possible prevention of weight gain by flax consumption warrants further investigation.

Altered plasma adipokines and markers of oxidative stress suggest increased risk of cardiovascular disease in First Nation youth with obesity or type 2 diabetes mellitus

Objective:  To evaluate cardiovascular disease risk in First Nation youth with and without type 2 diabetes mellitus (T2DM) or obesity by comparing pro‐ and anti‐inflammatory adipokines, markers of oxidative stress and the plasma phospholipid fatty acid profile.

Resveratrol prevents norepinephrine induced hypertrophy in adult rat cardiomyocytes, by activating NO-AMPK pathway

Increased adrenergic drive is a major factor influencing the development of pathological cardiac hypertrophy, a stage which precedes overt heart failure. We examined the effect of resveratrol, a polyphenol (found predominantly in grapes), in preventing norepinephrine induced hypertrophy of adult cardiomyocyte, and the role of nitric oxide (NO) and adenosine monophosphate kinase (AMPK) in the effects of resveratrol. Cardiomyocytes isolated from adult rats were pretreated, or not, with resveratrol and then exposed to norepinephrine for 24h. In other experiments cardiomyocytes were also treated with different pharmacological inhibitors of NO synthase, AMPK and sirtuin for elucidating the signaling pathways underlying the effect of resveratrol. In order to validate the role of these signaling molecules in the in vivo settings, we also examined hearts from resveratrol treated spontaneously hypertensive rats (SHR), a genetic model of essential hypertension. Cardiomyocyte hypertrophy was determined by morphometry and (3)H-phenylalanine incorporation assay. NO levels and AMPK activity were measured using a specific assay kit and western blot analysis respectively. In vitro, resveratrol prevented the norepinephrine-induced increase in cardiomyocytes size and protein synthesis. Pharmacological inhibition of NO-AMPK signaling abolished the anti-hypertrophic action of resveratrol. Consistent with the in vitro findings, the anti-hypertrophic effect of resveratrol in the SHR model was associated with increases in NO and AMPK activity. This study demonstrates that NO-AMPK signaling is linked to the anti-hypertrophic effect of resveratrol in adult cardiomyocytes in vitro, and in the SHR model in vivo.

Modulation of lipid droplet size and lipid droplet proteins by trans-10,cis-12 conjugated linoleic acid parallels improvements in hepatic steatosis in obese, insulin-resistant rats.

The isomer-specific effects of conjugated linoleic acid (CLA) on hepatic steatosis were assessed in fa/fa Zucker rats, a model for insulin resistance and the metabolic syndrome. Eight weeks of feeding trans-10,cis-12 CLA significantly improved glucose tolerance without changing body weight or visceral adipose mass. The trans-10,cis-12 isomer was also associated with reduced liver lipid content, improved liver function and reduced inflammation; these effects were not observed in rats fed the cis-9,trans-11 CLA isomer. Reduced liver lipid content did not correlate with activation of AMP-activated protein kinase or suppressed activation of sterol-regulatory element binding protein-1, two key regulators of hepatic lipid metabolism. Interestingly, rats fed cis-9,trans-11 CLA had fewer cytoplasmic lipid droplets in hepatocytes compared to rats fed control diet, but these droplets were larger in size. Conversely, fa/fa rats fed the trans-10,cis-12 CLA isomer had greater numbers of hepatic lipid droplets that were smaller in size, resulting in overall lower total lipid within these droplets. Changes in lipid droplets were associated with lower hepatic levels of PERILIPIN-2 (formerly known as adipophilin) in rats fed trans-10,cis-12 CLA, whereas amounts of other members of the PERILIPIN family of lipid droplet proteins were unaffected by dietary CLA. However, CLA isomers differentially affected the subcellular localization of these proteins. Treatment of H4IIE rat hepatoma cells with CLA isomers neither prevented nor reversed, but rather induced cytoplasmic lipid droplet formation, suggesting that the anti-steatotic effects of trans-10,cis-12 CLA are likely indirect and potentially mediated via increased lipid utilization by peripheral tissues.

Consumption of buckwheat modulates the post-prandial response of selected gastrointestinal satiety hormones in individuals with type 2 diabetes mellitus.

PURPOSE In healthy participants and those with diet-controlled type 2 diabetes (T2DM), to (1) compare the acute 3-hour post-prandial response of glucose, insulin and other gastrointestinal hormones known to influence food intake and glucose metabolism after consumption of a food product made from whole grain buckwheat flour versus rice flour; (2) determine the effect of daily consumption of a food product made from whole grain buckwheat flour on fasting glucose, lipids and apolipoproteins. METHODS Healthy participants or those with T2DM consumed either buckwheat or rice crackers. Blood samples were collected at baseline and 15, 30, 45, 60, 120 and 180minutes after consumption. In a second phase of the study, participants consumed one serving of buckwheat crackers daily for 1week; fasting blood samples from day 1 and day 7 were analyzed. RESULTS Post-prandial plasma glucagon-like peptide-1, glucose-dependent insulinotropic peptide and pancreatic polypeptide were altered after consuming buckwheat versus rice crackers. Interestingly, changes in these hormones did not lead to changes in post-prandial glucose, insulin or C-peptide concentrations. Significant correlations were observed between both fasting concentrations and post-prandial responses of several of the hormones examined. Interestingly, certain correlations were present only in the healthy participant group or the T2DM group. There was no effect of consuming buckwheat for one week on fasting glucose, lipids or apolipoproteins in either the healthy participants or those with T2DM. CONCLUSIONS Although the buckwheat cracker did not modify acute glycemia or insulinemia, it was sufficient to modulate gastrointestinal satiety hormones.

Glucose transporters: cellular links to hyperglycemia in insulin resistance and diabetes.

Abnormal expression and/or function of mammalian hexose transporters contribute to the hallmark hyperglycemia of diabetes. Due to different roles in glucose handling, various organ systems possess specific transporters that may be affected during the diabetic state. Diabetes has been associated with higher rates of intestinal glucose transport, paralleled by increased expression of both active and facilitative transporters and a shift in the location of transporters within the enterocyte, events that occur independent of intestinal hyperplasia and hyperglycemia. Peripheral tissues also exhibit deregulated glucose transport in the diabetic state, most notably defective translocation of transporters to the plasma membrane and reduced capacity to clear glucose from the bloodstream. Expression of renal active and facilitative glucose transporters increases as a result of diabetes, leading to elevated rates of glucose reabsorption. However, this may be a natural response designed to combat elevated blood glucose concentrations and not necessarily a direct effect of insulin deficiency. Functional foods and nutraceuticals, by modulation of glucose transporter activity, represent a potential dietary tool to aid in the management of hyperglycemia and diabetes.