Dietary omega-3 fatty acid and omega-3: omega-6 fatty acid ratio predict improvement in glucose disturbances in Japanese Brazilians

Objective: We investigated whether lifestyle-induced changes in dietary fat quality are related to Improvements on glucose metabolism disturbances in Japanese Brazilians at high risk of type 2 diabetes Methods: One hundred forty-eight first- and second-generation subjects with impaired glucose tolerance or impaired fasting glycemia who attended a lifestyle intervention program for 12 mo were studied in the city of Bauru. State of Sao Paulo, Brazil Dietary fatty acid intakes at baseline and after 12 mo were estimated using three 24-h recalls. The effect of dietary fat intake on glucose metabolism was investigated by multiple logistic regression models Results: At baseline, mean standard deviation age and body mass index were 60 II y and 25 5 4.2 kg/m2, respectively After 12 mo. 92 subjects had normal plasma glucose levels and 56 remained in prediabetic conditions. Using logistic regression models adjusted for age, gender, generation, basal intake of explanatory nutrient, energy intake, physical activity, and waist circumference, the odds ratios (95% confidence intervals) for reversion to normoglycemia were 3 14 (1 22-8 10) in the second wrote of total w-3 fatty acid, 4 26 (1.34-13 57) in the second tunic of eicosapentaenoic acid, and 280 (1 10-7.10) in the second tertile of linolenic acid. Similarly. subjects in the highest wrote of w-3.w-6 fatty acid ratio showed a higher chance of improving glucose disturbances (2 51, 1.01-6.37) Conclusions: Our findings support the evidence of an independent protective effect of omega-3 fatty acid and of a higher omega-3:omega-6 fatty acid ratio on the glucose metabolism of high-risk individuals (C) 2010 Elsevier Inc All rights reserved.

Oleic Acid Modulates Metabolic Substrate Channeling during Glucose-Stimulated Insulin Secretion via NAD(P)H Oxidase

Positive acute effects of fatty acids (FA) on glucose-stimulated insulin secretion (GSIS) and reactive oxygen species (ROS) formation have been reported. However, those studies mainly focused on palmitic acid actions, and reports on oleic acid (OA) are scarce. In this study, the effect of physiological OA levels on beta-cell function and the mechanisms involved were investigated. Analyses of insulin secretion, FA and glucose oxidation, and ROS formation showed that, at high glucose concentration, OA treatment increases GSIS in parallel with increased ROS content. At high glucose, OA oxidation was increased, accompanied by a suppression of glucose oxidation. Using approaches for protein knockdown of FA receptor G protein-coupled receptor 40 (GPR40) and of p47(PHOX), a reduced nicotinamide adenine dinucleotide phosphate [NAD(P) H] oxidase component, we observed that GPR40 does not mediate OA effects on ROS formation and GSIS. However, in p47(PHOX) knockdown islets, OA-induced ROS formation and the inhibitory effect of OA on glucose metabolism was abolished. Similar results were obtained by pharmacological inhibition of protein kinase C, a known activator of NAD(P) H oxidase. Thus, ROS derived from OA metabolism via NAD(P) H oxidase are an inhibitor of glucose oxidation. Put together, these results indicate that OA acts as a modulator of glucose oxidation via ROS derived from its own metabolism in beta-cells. (Endocrinology 152: 3614-3621, 2011)

Long-term 5-year effects of a reduced-fat diet intervention in individuals with glucose intolerance

OBJECTIVE: To determine whether reducing dietary fat would reduce body weight and improve long-term glycemia in people with glucose intolerance. RESEARCH DESIGN AND METHODS: A 5-year Follow-up of a 1-year randomized controlled trial of a reduced-fat ad libitum diet versus a usual diet. Participants with glucose intolerance (2-h blood glucose 7.0-11.0 mmol/l) were recruited from a Workforce Diabetes Survey. The group that was randomized to a reduced-fat diet participated in monthly small-group education sessions on reduced-fat eating for 1 year. Body weight and glucose tolerance were measured in 136 participants at baseline 6 months, and 1 year (end of intervention), with follow-up at 2 years (n = l04), 3 years (n = 99), and 5 years (n = 103). RESULTS: Compared with the control group, weight decreased in the reduced-fat-diet group (P < 0.0001); the greatest difference was noted at 1 year (-3.3 kg), diminished at subsequent follow-up (-3.2 kg at 2 years and -1.6 kg at 3 years), and was no longer present by 5 years (1.1 kg). Glucose tolerance also improved in patients on the reduced-fat diet; a lower proportion had type 2 diabetes or impaired glucose tolerance at 1 year (47 vs. 67%, P < 0.05), but in subsequent years, there were no differences between groups. However, the more compliant 50% of the intervention group maintained lower fasting and 2-h glucose at 5 years (P = 0.041 and P = 0.026 respectively) compared with control subjects. CONCLUSIONS: The natural history for people at high risk of developing type 2 diabetes is weight gain and deterioration in glucose tolerance. This process may be ameliorated through adherence to a reduced fat intake

Effects of melatonin on hemolymph glucose and lactate concentrations in the fiddler crab, uca pugilator

Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine hormone produced by the pineal gland that works to regulate sleep/wake cycles and activity rhythms. The effects of melatonin in metabolism are far from understood. Melatonin was injected into the fiddler crab, Uca pugilator, to investigate the effects of melatonin on hemolymph glucose and lactate levels. Following injection at t=O, hemolymph samples were collected at t=O.5, 1.0, 1.5 and 5.0 hours. Melatonin caused a decrease in the stress response to injection and also caused delayed hyperglycemia. Melatonin-injected crabs also retained the glucose and lactate rhythymicity when compared to saline-injected crabs. Glucose and lactate rhythms followed the same pattern indicating that the cycles are coupled. Also, melatonin was synthesized using tbe Fischer Indole synthesis and characterized using H?NMR. The synthetic melatonin demonstrated biological activity when injected into the crabs as when compared to pure melatonin on the effects on glucose and lactate concentrations. Overall, melatonin influences both glucose metabolism and the production of lactate.

Potential role of nitric oxide in contraction-stimulated glucose uptake and mitochondrial biogenesis in skeletal muscle

• 1. The present review discusses the potential role of nitric oxide (NO) in the: (i) regulation of skeletal muscle glucose uptake during exercise; and (ii) activation of mitochondrial biogenesis after exercise.
• 2. We have shown in humans that local infusion of an NO synthase inhibitor during exercise attenuates increases in skeletal muscle glucose uptake without affecting blood flow. Recent studies from our laboratory in rodents support these findings in humans, although rodent studies from other laboratories have yielded conflicting results.
• 3. There is clear evidence that NO increases mitochondrial biogenesis in non-contracting cells and that NO influences basal skeletal muscle mitochondrial biogenesis. However, there have been few studies examining the potential role of NO in the activation of mitochondrial biogenesis following an acute bout of exercise or in response to exercise training. Early indications are that NO is not involved in regulating the increase in mitochondrial biogenesis that occurs in response to exercise.
• 4. Exercise is considered the best prevention and treatment option for diabetes, but unfortunately many people with diabetes do not or cannot exercise regularly. Alternative therapies are therefore critical to effectively manage diabetes. If skeletal muscle NO is found to play an important role in regulating glucose uptake and/or mitochondrial biogenesis, pharmaceutical agents designed to mimic these effects of exercise may improve glycaemic control.

Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance. The Australian Diabetes, Obesity and Lifestyle Study (AusDiab)

Background--Diabetes mellitus increases the risk of cardiovascular disease (CVD) and all-cause mortality. The relationship between milder elevations of blood glucose and mortality is less clear. This study investigated whether impaired fasting glucose and impaired glucose tolerance, as well as diabetes mellitus, increase the risk of all-cause and CVD mortality.

Methods and Results--In 1999 to 2000, glucose tolerance status was determined in 10 428 participants of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). After a median follow-up of 5.2 years, 298 deaths occurred (88 CVD deaths). Compared with those with normal glucose tolerance, the adjusted all-cause mortality hazard ratios (HRs) and 95% confidence intervals (CIs) for known diabetes mellitus and newly diagnosed diabetes mellitus were 2.3 (1.6 to 3.2) and 1.3 (0.9 to 2.0), respectively. The risk of death was also increased in those with impaired fasting glucose (HR 1.6, 95% CI 1.0 to 2.4) and impaired glucose tolerance (HR 1.5, 95% CI 1.1 to 2.0). Sixty-five percent of all those who died of CVD had known diabetes mellitus, newly diagnosed diabetes mellitus, impaired fasting glucose, or impaired glucose tolerance at baseline. Known diabetes mellitus (HR 2.6, 95% CI 1.4 to 4.7) and impaired fasting glucose (HR 2.5, 95% CI 1.2 to 5.1) were independent predictors for CVD mortality after adjustment for age, sex, and other traditional CVD risk factors, but impaired glucose tolerance was not (HR 1.2, 95% CI 0.7 to 2.2).

Conclusions--This study emphasizes the strong association between abnormal glucose metabolism and mortality, and it suggests that this condition contributes to a large number of CVD deaths in the general population. CVD prevention may be warranted in people with all categories of abnormal glucose metabolism.

Gender differences in the prevalence of impaired fasting glycaemia and impaired glucose tolerance in Mauritius. Does sex matter?

Objective: To examine gender differences in the characteristics and prevalence of various categories of glucose tolerance in a population study in Mauritius.

Research design and methods: In 1998, a community-based cross-sectional survey was conducted in Mauritius. Categories of glucose metabolism were determined in 5388 adults, with an oral glucose tolerance test given to those who did not have previously diagnosed diabetes (n = 4036). Other cardiovascular risk factors were assessed among those without known diabetes.

Results: For men and women the prevalence of diabetes (22.0 vs. 21.8%, respectively) and the prevalence of coexisting impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) (3.2 vs. 2.9%) were similar. However, men were twice as likely as women to have isolated IFG [5.1% (4.2–6.0) vs. 2.9% (2.3–3.5)], despite being younger, thinner and with lower plasma insulin but higher lipids. Conversely, the prevalence of isolated IGT was lower in men [9.0% (7.9–10.2) vs. 13.9% (12.6–15.1)]. Among non-diabetic individuals, fasting glucose was higher in men than women, whereas 2-h glucose was higher in women. In people without diabetes, women had significantly higher body mass index, beta cell function (HOMA-B), fasting and 2-h insulin than men and significantly lower waist-hip ratios, waist circumference, insulin sensitivity (HOMA-S) and triglycerides.

Conclusion: In Mauritius, the distribution of impaired glucose metabolism differs by sex. The observation that IFG is more prevalent in men and IGT more prevalent in women raises important questions about their underlying aetiology and the ability of the current glucose thresholds to equally identify men and women at high-risk of developing diabetes. IFG should be seen as a complimentary category of abnormal glucose tolerance, rather than a replacement for IGT.

The effect of vitamin : a deficiency on glucose uptake in the rat

This thesis describes an investigation of the effects of vitamin A deficiency on gut function, The central hypothesis to be tested was that acute vitamin A deficiency affects glucose uptake from the small intestine- The hypothesis was tested using a system involving perfusion of isolated segments of the small intestine in the anaesthetized rat. The system was used to study effects on glucose uptake under steady-state conditions. In the initial part of the study, experiments were diverted towards setting up the system for measuring steady-state uptake, and determining the relative contributions of active uptake and diffusion. Phenol red was found to be a reliable non-absorbable marker for determining net water movement. Phlorizin, generally at 1 mmol/L, was used as a competitive (reversible) inhibitor of active uptake. It is difficult however to confirm complete inhibition of active uptake by phlorizin because of the limited solubility of the inhibitor. The kinetics of glucose uptake f ram intra-luminal maltose were found to be, in general, not significantly different from those applying to the uptake of glucose from an equivalent glucose solution. Maltase activity in the perfused gut segment was found to be sufficient to hydrolyse most of the maltose (80 per cent or more) in the solution being perfused, a much greater proportion than was absorbed. Glucose absorptive capacity, measured on an intestinal dry weight basis, was greatest in the duodenum and progressively less in the jejunum and ileum. The rate of water uptake f ran the gut was increased by the presence of glucose in the lumen, and was linked to glucose uptake as shown by the inhibition of water uptake by phlorizin. Uptake of glucose by solvent drag was demonstrated by showing an increased rate of glucose uptake when the rate of water uptake was increased by perfusing a solution of reduced osmotic pressure. In the experiment a low intra-luminal glucose concentration was used to preclude net uptake by diffusion and active uptake was blocked with phlorizin. This process was further investigated using streptozotocin-diabetic rats in which the diabetes establishes a hyperosomotic blood with hyperglycaemia. Uptake by solvent drag was more obvious in diabetic animals. A back-diffusion (exsorption) of glucose from the tissues to the lumen was also shown; the rate being proportional to plasma glucose concentration. Vitamin A deficiency was established in weanling rats after 6-7 weeks feeding on a diet based on wheat starch, coconut oil, and casein washed with hot ethanol, together with vitamins and minerals. The vitamin A deficiency led to classic eye signs and was reversed by the addition to the diet of retinoic acid (5 g/g diet). Vitamin A deficiency decreased intestinal mucus production (dry weight) but had no detectable effect on the histology of the villous epithelium as shown under the light microscope. Using perfusion experiments it was shown that vitamin A deficiency had no significant effect on the rate of active uptake of glucose, but that deficiency increased the rate of passive uptake.

Interaction of dietary fibre, carbohydrate metabolism and diabetes in the rat

It is currently accepted that the most appropriate diet in the treatment of non-insulin-dependent diabetes mellitus "e;NIDDM"e; is high in carbohydrates, high in fibre and low in fat. Dietary fibre reduces the rate of carbohydrate absorption, which may have a beneficial effect on insulin action. Furthermore, high fibre diets also increase the amount of carbohydrates which are not absorbed from the small intestine. These malabsorbed carbohydrates are fermented by the bacterial population in the large intestine, producing short chain fatty acids "e;SCFA"e;, including propionate, which has been shown to alter liver carbohydrate metabolism. This thesis investigated the actions of slowed carbohydrate absorption and carbohydrate malabsorption in streptozotocin-induced "e;STZ"e; diabetic rats. High carbohydrate diet supplemented with guar gum, a soluble dietary fibre, fed to STZ diabetic rats improved insulin sensitivity. investigation of the alterations in the stomach and small intestine demonstrated that guar increased the viscosity of the meal in the intestine. The action of increased fermentation, producing more propionate, was investigated by supplementing propionate into the diets of STZ diabetic rats or when perfused into isolated rat livers. No changes in insulin action or liver glucose metabolism were measured. in addition, it was shown that guar gum reduces food intake in STZ diabetic rats. Mild reductions in food intake in STZ diabetic rats were shown to increase insulin action. In summary, STZ diabetic rats fed high carbohydrate, high fibre diets reductions in food consumption and slowed carbohydrate absorption are important factors which may lower blood glucose concentrations and increase insulin action. increased SCFA production is unlikely to contribute significantly to the improvements in insulin action.

Breaking up prolonged sitting reduces postprandial glucose and insulin responses

OBJECTIVE--Observational studies show breaking up prolonged sitting has beneficial associations with cardiometabolic risk markers, but intervention studies are required to investigate causality. We examined the acute effects on postprandial glucose and insulin levels of uninterrupted sitting compared with sitting interrupted by brief bouts of light- or moderate-intensity walking.

RESEARCH DESIGN AND METHODS--Overweight/obese adults (n = 19), aged 45-65 years, were recruited for a randomized three-period, three-treatment acute crossover trial: I) uninterrupted sitting; 2) seated with 2-min bouts of light-intensity walking every 20 rain; and 3) seated with 2-min bouts of moderate-intensity walking every 20 min. A standardized test drink was provided after an initial 2-h period of uninterrupted sitting. The positive incremental area under curves (iAUC) for glucose and insulin (mean [95% CI]) for the 5 h after the test drink (75 g glucose, 50 g fat) were calculated for the respective treatments.

RESULTS--The glucose iAUC (mmol/L) x h after both activity-break conditions was reduced (light: 5.2 [4.1-6.6]; moderate: 4.9 [3.8-6.1]; both P < 0.01) compared with uninterrupted sitting (6.9 [5.5-8.7]). Insulin iAUC (pmol/L) x h was also reduced with both activity-break conditions (light: 633.6 [552.4-727.1]; moderate: 637.6 [555.5-731.9], P < 0.0001) compared with uninterrupted sitting (828.6 [722.0-950.9]).

CONCLUSIONS--Interrupting sitting time with short bouts of light- or moderate-intensity walking lowers postprandial glucose and insulin levels in overweight/obese adults. This may improve glucose metabolism and potentially be an important public health and clinical intervention strategy for reducing cardiovascular risk.

The intravenous glucose tolerance and postprandial glucose tests may present different responses in the evaluation of obese dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of melatonin on the oxidative metabolism of colostrum phagocytes of diabetic women

Aim: the aim of this study was verified the ability of melatonin hormone to modulate the oxidative metabolism of colostral phagocytes from diabetic mothers. Methods: based on 100g-OGTT and glucose profile analysis subjects were allocated into two groups: Non-diabetic (ND-10) and Diabetic (DM-8). Cells were separated by a Ficoll-Paque gradient and the oxidative metabolism was available thought superoxide release by colostrum phagocytes using the cytochrome C method. Results: melatonin hormone increased superoxide release by colostrum phagocytes of ND and decreased these release in colostrum phagocytes of DM mothers. Conclusion: the results suggest that the melatonin hormone can modulate the oxidative metabolism of phagocytes and an existence of relationship between control of glucose metabolism and melatonin action in colostrum phagocytes.

Gluconeogenesis and glucose replacement rate during long-term fasting of Japanese quails

Gluconeogenic activity and kinetic parameters of glucose metabolism were estimated during the different phases of prolonged food deprivation in quails. Gluconeogenic activity, estimated from the rate of increase of incorporation of (HCO3-)-C-14 into circulating glucose, was significantly higher in fasted quails than in fed birds, whatever the period of food deprivation. However, gluconeogenic activity during phase II, although higher than in the fed state, was significantly lower than in quails fasted for 2 days (phase I) or in those on the final (phase III) period of starvation. Gluconeogenic activity did not differ significantly in birds from phases I and III. Rates of glucose replacement, estimated with [6-H-3]-glucose, were very high (20.5 mg . kg(-1). min(-1)) in fed quails and were markedly reduced (to about 42% of fed values) by fasting, no difference being observed between quails fasted for 2 and 5 days. Because of the poor condition of the birds, glucose replacement rates could not be measured during phase III. The present data are the first to provide direct evidence for the changes in gluconeogenesis which occur during prolonged food deprivation.