Lower nocturnal blood glucose response to a potato-based mixed evening meal compared to rice in individuals with type 2 diabetes.

BACKGROUND & AIMS: Guidelines for reducing postprandial blood glucose concentrations include avoiding high glycemic index (GI) foods, such as white potatoes. However, GI testing is often undertaken in the morning with foods consumed in isolation by non-clinical cohorts. We investigated the impact of potato preparation and consumption as part of a mixed-evening meal on postprandial and nocturnal glycemic responses, and postprandial insulin response, in individuals with Type 2 Diabetes Mellitus (T2DM). METHODS: In a randomized, cross-over design, 24 males and females (age 58.3 ± 9.3 y; BMI: 31.7 ± 6.8 kg/m2) with T2DM (diet or metformin controlled) completed four experimental trials after consuming a standardized breakfast (25% daily energy intake (EI)) and lunch (35% EI). Dinner (40% EI) was consumed at 1800 h being either: 1) boiled potato (BOIL); 2) roasted potato (ROAST); 3) boiled potato cooled for 24 h (COOLED); or 4) basmati rice (CONTROL). Each meal contained 50% carbohydrate, 30% fat and 20% protein. Blood samples were collected prior to, immediately post meal and at 30-min intervals for a further 120 min. A continuous glucose monitor was worn to assess nocturnal interstitial glucose concentrations. RESULTS: No differences were detected in postprandial venous glucose area under the curve (iAUC) between CONTROL and all three potato conditions. Postprandial insulin iAUC was greater following COOLED compared to CONTROL (P = 0.003; 95% CI: 18.9-111.72 miU/mL). No significant differences between CONTROL and BOIL or ROAST were detected for postprandial insulin concentrations. All potato meals resulted in lower nocturnal glucose AUC than CONTROL (P < 0.001; 95% CI 4.15-15.67 mmol/L x h). CONCLUSION: Compared to an isoenergetic rice meal, boiled, roasted or boiled then cooled potato-based meals were not associated with unfavourable postprandial glucose responses or nocturnal glycemic control, and can be considered suitable for individuals with T2DM when consumed as part of a mixed-evening meal. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry https://www.anzctr.org.au/, ACTRN 12618000480280.

Chrono-nutrition for the prevention and treatment of obesity and type 2 diabetes: from mice to men.

The proliferation in the rate of diagnosis of obesity and type 2 diabetes mellitus continues unabated, with current recommendations for primary lifestyle changes (i.e. modification to dietary patterns) having a limited impact in reducing the incidence of these metabolic diseases. Part of the reason for the failure to alter nutritional practices is that current dietary recommendations may be unrealistic for the majority of adults. Indeed, round-the-clock access to energy-dense, nutrient-poor food makes long-term changes to dietary habits challenging. Hence, there is urgent need for innovations in the delivery of evidence-based diet interventions to rescue some of the deleterious effects on circadian biology induced by our modern-day lifestyle. With the growing appreciation that the duration over which food is consumed during a day has profound effects on numerous physiological and metabolic processes, we discuss dietary protocols that modify the timing of food intake to deliberately alter the feeding-fasting cycle. Such chrono-nutrition functions to optimise metabolism by timing nutrient intake to the acrophases of metabolic rhythms to improve whole-body insulin sensitivity and glycaemic control, and thereby positively impact metabolic health. Graphical abstract.

Single and Combined Effects of Beetroot Crystals and Sodium Bicarbonate on 4-km Cycling Time Trial Performance.

When ingested alone, beetroot juice and sodium bicarbonate are ergogenic for high-intensity exercise performance. This study sought to determine the independent and combined effects of these supplements. Eight endurance trained (VO2max 65 mL·kg·min-1) male cyclists completed four × 4-km time trials (TT) in a doubleblind Latin square design supplementing with beetroot crystals (BC) for 3 days (15 g·day-1 + 15 g 1 h before TT, containing 300 mg nitrate per 15 g), bicarbonate (Bi 0.3 g·kg-1 body mass [BM] in 5 doses every 15 min from 2.5 h before TT); BC+Bi or placebo (PLA). Subjects completed TTs on a Velotron cycle ergometer under standardized laboratory conditions. Plasma nitrite concentrations were significantly elevated only in the BC+Bi trial before the TT (1520 ± 786 nmol·L-1) compared with baseline (665 ± 535 nmol·L-1, p = .02) and the Bi and PLA conditions (Bi: 593 ± 203 nmol·L-1, p < .01; PLA: 543 ± 369 nmol·L-1, p < .01). Plasma nitrite concentrations were not elevated in the BC trial before the TT (1102 ± 218 nmol·L-1) compared with baseline (975 ± 607 nmol·L-1, p > .05). Blood bicarbonate concentrations were increased in the BC+Bi and Bi trials before the TT (BC+Bi: 30.9 ± 2.8 mmol·L-1; Bi: 31.7 ± 1.1 mmol·L-1). There were no differences in mean power output (386-394 W) or the time taken to complete the TT (335.8-338.1 s) between any conditions. Under the conditions of this study, supplementation was not ergogenic for 4-km TT performance.

Fenugreek increases insulin-stimulated creatine content in L6C11 muscle myotubes.

PURPOSE: Creatine uptake by muscle cells is increased in the presence of insulin. Accordingly, compounds with insulin-like actions may also augment creatine uptake. The aim of this study was to investigate whether Trigonella foenum-graecum (fenugreek), an insulin mimetic, increases total intracellular creatine levels in vitro. METHODS: Total cellular creatine content was measured fluorometrically in L6C11 muscle myotubes treated for 1, 4, and 24 h with 0.5 mM creatine (CR), CR and 20 µg/mL fenugreek seed extract (CR + FEN), CR and 100 nM insulin (CR + INS), and CR + INS + FEN (n = 6 per treatment group). Alterations in the expression of the sodium- and chloride-dependent creatine transporter, SLC6A8, and key signaling proteins in the PI3-K/Akt pathway were determined. RESULTS: Compared to control (CON), CR + INS + FEN increased total creatine content after 4 h (P < 0.05), whereas all conditions increased SLC6A8 protein expression above CON at this time (P < 0.05). Changes in insulin signaling were demonstrated via increases in AktThr308 phosphorylation, with CR + INS > CON and CR at 1 h (P < 0.05) and with CR + INS + FEN > CON, CR, and CR + INS at 4 h (P < 0.05). In contrast, no changes in PKCζ/λ or GLUT4 phosphorylation were detected. CONCLUSION: Fenugreek, when combined with insulin, modulates creatine content via a mechanism which is independent of the activity of SLC6A8, suggesting that an alternative mechanism is responsible for the regulation and facilitation of insulin-mediated creatine uptake in skeletal muscle cells.

Protein ingestion increases myofibrillar protein synthesis after concurrent exercise.

PURPOSE: We determined the effect of protein supplementation on anabolic signaling and rates of myofibrillar and mitochondrial protein synthesis after a single bout of concurrent training. METHODS: Using a randomized crossover design, eight healthy males were assigned to experimental trials consisting of resistance exercise (8 × 5 leg extension, 80% 1RM) followed by cycling (30 min at approximately 70% V˙O2peak) with either postexercise protein (PRO, 25-g whey protein) or placebo (PLA) ingestion. Muscle biopsies were obtained at rest and at 1 and 4 h after exercise. RESULTS: Akt and mTOR phosphorylation increased 1 h after exercise with PRO (175%-400%, P < 0.01) and was different from PLA (150%-300%, P < 0.001). Muscle RING finger 1 and atrogin-1 messenger RNA (mRNA) were elevated after exercise but were higher with PLA compared with those in PRO at 1 h (50%-315%, P < 0.05), whereas peroxisome proliferator-activated receptor gamma coactivator 1-alpha mRNA increased 4 h after exercise (620%-730%, P < 0.001), with no difference between treatments. Postexercise rates of myofibrillar protein synthesis increased above rest in both trials (75%-145%, P < 0.05) but were higher with PRO (67%, P < 0.05), whereas mitochondrial protein synthesis did not change from baseline. CONCLUSIONS: Our results show that a concurrent training session promotes anabolic adaptive responses and increases metabolic/oxidative mRNA expression in the skeletal muscle. PRO ingestion after combined resistance and endurance exercise enhances myofibrillar protein synthesis and attenuates markers of muscle catabolism and thus is likely an important nutritional strategy to enhance adaptation responses with concurrent training.

Single and combined effects of beetroot juice and caffeine supplementation on cycling time trial performance.

Both caffeine and beetroot juice have ergogenic effects on endurance cycling performance. We investigated whether there is an additive effect of these supplements on the performance of a cycling time trial (TT) simulating the 2012 London Olympic Games course. Twelve male and 12 female competitive cyclists each completed 4 experimental trials in a double-blind Latin square design. Trials were undertaken with a caffeinated gum (CAFF) (3 mg·kg(-1) body mass (BM), 40 min prior to the TT), concentrated beetroot juice supplementation (BJ) (8.4 mmol of nitrate (NO3(-)), 2 h prior to the TT), caffeine plus beetroot juice (CAFF+BJ), or a control (CONT). Subjects completed the TT (females: 29.35 km; males: 43.83 km) on a laboratory cycle ergometer under conditions of best practice nutrition: following a carbohydrate-rich pre-event meal, with the ingestion of a carbohydrate-electrolyte drink and regular oral carbohydrate contact during the TT. Compared with CONT, power output was significantly enhanced after CAFF+BJ and CAFF (3.0% and 3.9%, respectively, p < 0.01). There was no effect of BJ supplementation when used alone (-0.4%, p = 0.6 compared with CONT) or when combined with caffeine (-0.9%, p = 0.4 compared with CAFF). We conclude that caffeine (3 mg·kg(-1) BM) administered in the form of a caffeinated gum increased cycling TT performance lasting ∼50-60 min by ∼3%-4% in both males and females. Beetroot juice supplementation was not ergogenic under the conditions of this study.

Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise.

BACKGROUND: The major thiol-disulfide couple of reduced glutathione (GSH) and oxidized glutathione is a key regulator of major transcriptional pathways regulating aseptic inflammation and recovery of skeletal muscle after aseptic injury. Antioxidant supplementation may hamper exercise-induced cellular adaptations. OBJECTIVE: The objective was to examine how thiol-based antioxidant supplementation affects skeletal muscle's performance and redox-sensitive signaling during the inflammatory and repair phases associated with exercise-induced microtrauma. DESIGN: In a double-blind, crossover design, 10 men received placebo or N-acetylcysteine (NAC; 20 mg · kg(-1) · d(-1)) after muscle-damaging exercise (300 eccentric contractions). In each trial, muscle performance was measured at baseline, after exercise, 2 h after exercise, and daily for 8 consecutive days. Muscle biopsy samples from vastus lateralis and blood samples were collected before exercise and 2 h, 2 d, and 8 d after exercise. RESULTS: NAC attenuated the elevation of inflammatory markers of muscle damage (creatine kinase activity, C-reactive protein, proinflammatory cytokines), nuclear factor κB phosphorylation, and the decrease in strength during the first 2 d of recovery. NAC also blunted the increase in phosphorylation of protein kinase B, mammalian target of rapamycin, p70 ribosomal S6 kinase, ribosomal protein S6, and mitogen activated protein kinase p38 at 2 and 8 d after exercise. NAC also abolished the increase in myogenic determination factor and reduced tumor necrosis factor-α 8 d after exercise. Performance was completely recovered only in the placebo group. CONCLUSION: Although thiol-based antioxidant supplementation enhances GSH availability in skeletal muscle, it disrupts the skeletal muscle inflammatory response and repair capability, potentially because of a blunted activation of redox-sensitive signaling pathways. This trial was registered at clinicaltrials.gov as NCT01778309.

Oxidative stress-induced insulin resistance in skeletal muscle cells is ameliorated by gamma-tocopherol treatment.

BACKGROUND: Oxidative stress-induced reactive oxygen species are associated with the clinical manifestation of insulin resistance. Evidence suggests that antioxidant treatment may reduce this incidence. AIM OF THE STUDY: This study determined whether glucose oxidase (GO)-induced insulin resistance in cultured skeletal muscle cells could be ameliorated by pre-treatment with gamma-tocopherol (GT). METHODS: Insulin sensitivity in L6 myotubes was assessed by 2-deoxy-D: -[(3)H]-glucose uptake. The phosphorylation of distal insulin signaling proteins Akt and the Akt substrate AS160 were determined by western blot. RESULTS: One hour treatment with 100 mU/ml GO decreased insulin-stimulated glucose uptake (P < 0.001). Pre-treatment with GT either partially (100 microM) or completely (200 microM) restored insulin-stimulated glucose uptake in cells after GO-induced insulin resistance. GO-induced oxidative stress did not impair insulin stimulated phosphorylation of Akt or AS160, but 200 microM GT increased insulin-stimulated phosphorylation of these key signaling proteins (P < 0.05). CONCLUSIONS: High-dose (200 microM) GT treatment ameliorated oxidative stress-induced insulin resistance in cultured rat L6 skeletal muscle cells.

The effects of polyphenols in olive leaves on platelet function.

INTRODUCTION: The phenolic compounds of olive leaves and olive oils in the Mediterranean diet have been associated with a reduced incidence of heart disease. Accordingly, antioxidant-rich diets may prevent the deleterious effects of oxidative metabolism by scavenging free radicals, thus inhibiting oxidation and delaying atherosclerosis. The process involves phospholipase C activation and arachidonic acid metabolism, and is thought to reduce hydrogen peroxide (H(2)O(2)). In our study, an extract of Olea europaea L. leaves was used. The active phenolic compounds in this extract are part of the secoiridoid family, known for their capacity to scavenge H(2)O(2). The results from this study will help to improve our understanding of effects of polyphenol antioxidants in olive leaf extract on platelet function. METHODS: Full blood examination (FBE), platelet aggregation, and ATP release were performed on samples from fasting, normal, healthy male subjects. Platelet function at increasing concentrations of oleuropein was investigated through measures of platelet aggregation and ATP release from activated platelets. RESULTS: Blood analysis (n=11) revealed a significant dose-dependant reduction in platelet activity with olive extract concentrations of 1.0% v/v (P<0.001). ATP Release showed a similar pattern (P=0.02). CONCLUSIONS: Olive leaf polyphenols derived from O. europaea L. leaves inhibited in vitro platelet activation in healthy, non-smoking males. Further bioavailability studies need to be undertaken to determine the in vivo effect of extract on platelet function and to validate the present results.

Effects of gamma-tocopherol supplementation on thrombotic risk factors.

OBJECTIVE: The antioxidant activity of vitamin E is derived primarily from alpha-tocopherol (alpha-T) and gamma-tocopherol (gamma-T). Results of epidemiological studies have demonstrated an inverse relationship between vitamin E intake and coronary disease. However, the results of clinical trials using alpha-T are equivocal. We determined the effect of 5 weeks of 100 mg/d or 200 mg/d gamma-T supplementation on thrombotic markers such as platelet reactivity, lipid profile and the inflammation marker C-reactive protein (CRP). METHODS AND RESULTS: Fourteen healthy subjects consumed 100 mg/day while 13 consumed 200 mg/d of gamma-T and 12 received placebo (soybean capsules with less than 5 mg/d gamma-T) in a double-blinded parallel study design. Fasting pre and post dose blood samples were analysed. Blood gamma-T concentrations increased significantly (p<0.05) relative to dose during the intervention period. Both groups receiving active ingredients showed significantly lower platelet activation after supplementation (p<0.05). Subjects consuming 100 mg/d gamma-T had significantly decreased LDL cholesterol, platelet aggregation and mean platelet volume (MPV) (p<0.05). Little effect of gamma-T was observed on other parameters. CONCLUSIONS: These data suggest that gamma-T supplementation may have a permissive role in decreasing the risk of thrombotic events by improving lipid profile and reducing platelet activity.

Tissue-specific effects of rosiglitazone and exercise in the treatment of lipid-induced insulin resistance.

Both pharmacological intervention (i.e., thiazolidinediones [TZDs]) and lifestyle modification (i.e., exercise training) are clinically effective treatments for improving whole-body insulin sensitivity. However, the mechanism(s) by which these therapies reverse lipid-induced insulin resistance in skeletal muscle is unclear. We determined the effects of 4 weeks of rosiglitazone treatment and exercise training and their combined actions (rosiglitazone treatment and exercise training) on lipid and glucose metabolism in high-fat-fed rats. High-fat feeding resulted in decreased muscle insulin sensitivity, which was associated with increased rates of palmitate uptake and the accumulation of the fatty acid metabolites ceramide and diacylglycerol. Impairments in lipid metabolism were accompanied by defects in the Akt/AS160 signaling pathway. Exercise training, but not rosiglitazone treatment, reversed these impairments, resulting in improved insulin-stimulated glucose transport and increased rates of fatty acid oxidation in skeletal muscle. The improvements to glucose and lipid metabolism observed with exercise training were associated with increased AMP-activated protein kinase alpha1 activity; increased expression of Akt1, peroxisome proliferator-activated receptor gamma coactivator 1, and GLUT4; and a decrease in AS160 expression. In contrast, rosiglitazone treatment exacerbated lipid accumulation and decreased insulin-stimulated glucose transport in skeletal muscle. However, rosiglitazone, but not exercise training, increased adipose tissue GLUT4 and acetyl CoA carboxylase expression. Both exercise training and rosiglitazone decreased liver triacylglycerol content. Although both interventions can improve whole-body insulin sensitivity, our results show that they produce divergent effects on protein expression and triglyceride storage in different tissues. Accordingly, exercise training and rosiglitazone may act as complementary therapies for the treatment of insulin resistance.

Postexercise muscle triacylglycerol and glycogen metabolism in obese insulin-resistant zucker rats.

OBJECTIVE: To determine the impact of insulin resistance and obesity on muscle triacylglycerol (IMTG) and glycogen metabolism during and after prolonged exercise. RESEARCH METHODS AND PROCEDURES: Female lean (fa/?; N = 40, ZL) and obese insulin-resistant (fa/fa; N = 40, ZO) Zucker rats performed an acute bout of swimming exercise (8 times for 30 minutes) followed by 6 hours of carbohydrate supplementation (CHO) or fasting (FAST). IMTG and glycogen were measured in the extensor digitorum longus (EDL) and red vastus lateralis (RVL) muscles. RESULTS: Despite resting IMTG content being 4-fold higher in ZO compared with ZL rats, IMTG levels were unchanged in either EDL or RVL muscles immediately after exercise. Resting glycogen concentration in EDL and RVL muscles was similar between genotypes, with exercise resulting in glycogen use in both muscles from ZL rats (approximately 85%, p < 0.05). However, in ZO rats, there was a much smaller decrease in postexercise glycogen content in both EDL and RVL muscles (approximately 30%). During postexercise recovery, there was a decrease in EDL muscle levels of IMTG in ZL rats supplemented with CHO after 30 and 360 minutes (p < 0.05). In contrast, IMTG content was increased above resting levels in RVL muscles of ZO rats fasted for 360 minutes. Six hours of CHO refeeding restored glycogen content to resting levels in both muscles in ZL rats. However, after 6 hours of FAST in ZO animals, RVL muscle glycogen content was still lower than resting levels (p < 0.05). At this time, IMTG levels were elevated above basal (p < 0.05). DISCUSSION: In both healthy and insulin-resistant skeletal muscle, there was negligible net IMTG degradation after a single bout of prolonged exercise. However, during postexercise recovery, there was differential metabolism of IMTG between phenotypes.

Effect of increased fat availability on metabolism and exercise capacity.

Several procedures have been utilized to elevate plasma free fatty acid (FFA) concentration and increase fatty acid (FA) delivery to skeletal muscle during exercise. These include fasting, caffeine ingestion, L-carnitine supplementation, ingestion of medium-chain and long-chain triglyceride (LCT) solutions, and intravenous infusion of intralipid emulsions. Studies in which both untrained and well-trained subjects have ingested LCT solutions or received an infusion of intralipid (in combination with an injection of heparin) before exercise have reported significant reductions in whole-body carbohydrate oxidation and decreased muscle glycogen utilization during both moderate and intense dynamic exercise lasting 15-60 min. The effects of increased FA provision on rates of muscle glucose uptake during exercise are, however, equivocal. Despite substantial muscle glycogen sparing (15-48% compared with control), exercise capacity is not systematically improved in the face of increased FA availability.