Prebiotic Inulin Supplementation and Peripheral Insulin Sensitivity in adults at Elevated Risk for Type 2 Diabetes: A Pilot Randomized Controlled Trial.

Prediabetes affects 84.1 million adults, and many will progress to type 2 diabetes (T2D). The objective of this proof-of-concept trial was to determine the efficacy of inulin supplementation to improve glucose metabolism and reduce T2D risk. Adults (n = 24; BMI: 31.3 ± 2.9 kg/m2; age: 54.4 ± 8.3 years) at risk for T2D were enrolled in this controlled feeding trial and consumed either inulin (10 g/day) or placebo (maltodextrin, 10 g/day) for six weeks. Assessments included peripheral insulin sensitivity, fasting glucose, and insulin, HOMA-IR, in vivo skeletal muscle substrate preference, Bifidobacteria copy number, intestinal permeability, and endotoxin concentrations. Participant retention was 92%. There were no baseline group differences except for fasting insulin (p = 0.003). The magnitude of reduction in fasting insulin concentrations with inulin (p = 0.003, inulin = Δ-2.9, placebo = Δ2.3) was attenuated after adjustment for baseline concentrations (p = 0.04). After adjusting for baseline values, reduction in HOMA-IR with inulin (inulin = Δ-0.40, placebo=Δ0.27; p = 0.004) remained significant. Bifidobacteria 16s increased (p = 0.04; inulin = Δ3.1e9, placebo = Δ-8.9e8) with inulin supplementation. Despite increases in gut Bifidobacteria, inulin supplementation did not improve peripheral insulin sensitivity. These findings question the need for larger investigations of inulin and insulin sensitivity in this population.

Dietary and Biological Assessment of the Omega-3 Status of Collegiate Athletes: A Cross-Sectional Analysis.

Omega-3 fatty acids (ω-3 FA) are associated with cardiovascular health, brain function, reduction of inflammation, and several other physiological roles of importance to competitive athletes. The ω-3 FA status of National Collegiate Athletic Association (NCAA) Division I athletes has not been well-described. The purpose of this study was to evaluate the ω-3 FA status of NCAA Division I athletes using dietary and biological assessment methodology. Athletes from nine NCAA Division I institutions from throughout the U.S. (n = 1,528, 51% male, 34 sports represented, 19.9 ± 1.4 years of age) completed a food frequency questionnaire (FFQ) to assess ω-3 FA from diet and supplements. Omega-3 Index (O3i) was evaluated in a sub-set of these participants (n = 298, 55% male, 21 sports represented, 20.0 ± 1.3 years of age) using dried blood spot sampling. Only 6% (n = 93) of athletes achieved the Academy of Nutrition & Dietetics' recommendation to consume 500 mg DHA+EPA per day. Use of ω-3 FA supplements was reported by 15% (n = 229) of participants. O3i was 4.33 ± 0.81%, with no participants meeting the O3i benchmark of 8% associated with the lowest risk of cardiovascular disease. Every additional weekly serving of fish or seafood was associated with an absolute O3i increase of 0.27%. Overall, sub-optimal ω-3 FA status was observed among a large, geographically diverse group of male and female NCAA Division I athletes. These findings may inform interventions aimed at improving ω-3 FA status of collegiate athletes. Further research on athlete-specific ω-3 FA requirements is needed.

Effects of Seasonal Vitamin D3 Supplementation on Strength, Power, and Body Composition in College Swimmers.

The purpose of this study was to evaluate the impact of fall season vitamin D3 supplementation on strength/power, body composition, and anabolic hormones in swimmers with optimal vitamin D status at summer's end. Male and female National Collegiate Athletic Association Division I swimmers (N = 19) with optimal 25-hydroxyvitamin D [25(OH)D] randomly received 5,000 IU of vitamin D3 (VITD) or placebo (PLA) daily for 12 weeks while participating in swimming and strength and conditioning training (August-November). Before and after the intervention, the participants underwent blood sampling for analysis of serum 25(OH)D, parathyroid hormone, total testosterone, free testosterone, sex hormone-binding globulin, and insulin-like growth factor 1, dual-energy X-ray absorptiometry, and strength/power testing (bench press, squat, dead lift, standing broad jump, vertical jump, and dips and pull-ups). Sex was used as a covariate for analyses. The 25(OH)D was decreased by 44% in PLA (p < .05) and increased by 8% in VITD over the 12 weeks. Fat-free mass increased in VITD (56.4-59.1 kg; p < .05), but not PLA (59.4-59.7 kg; p < .01). Significant Group × Time interaction effects were observed for dead lift (F = 21.577, p < .01) and vertical jump (F = 11.219, p < .01), but no other strength/power tests. Total testosterone decreased similarly in both groups, but free testosterone decreased and sex hormone-binding globulin increased only in PLA (p < .01). There were no group differences or changes in insulin-like growth factor 1 with the intervention. The findings suggest that vitamin D supplementation is an efficacious strategy to maintain 25(OH)D during the fall season training and to enhance some aspects of strength/power and fat-free mass in swimmers. Further research on the relationship between vitamin D and anabolic hormones is needed.

Vitamin D Practice Patterns in National Collegiate Athletic Association Division I Collegiate Athletics Programs.

CONTEXT: Vitamin D status has been associated with performance, health, and well-being in athletic populations. The measurement of vitamin D status via 25-hydroxyvitamin D [25(OH)D] testing has increased in the general population, as has vitamin D supplement use. It is unclear if similar patterns exist in collegiate athletics programs. OBJECTIVE: To describe the clinical care related to the prevention, evaluation, and treatment of vitamin D deficiency and insufficiency used by sports medicine providers with National Collegiate Athletic Association (NCAA) Division I programs. DESIGN: Cross-sectional study. SETTING: Population-based online survey. PATIENTS OR OTHER PARTICIPANTS: All NCAA Division I head athletic trainers. MAIN OUTCOME MEASURE(S): Information related to 25(OH)D testing, vitamin D supplementation, vitamin D-related protocols and procedures, and characteristics of athletic programs and participants. RESULTS: We received 249 responses (72% response rate). Use of 25(OH)D testing was described by 68% of participants, with the most common indicators being health status/history (78%) and injury status/history (74%). One-fifth of participants stated that vitamin D testing was conducted as screening (without a specific cause or indication). Target blood vitamin D concentrations were highly variable. A range of 8 to 1660 annual vitamin D blood tests was reported at a cost of <$50 (8%), $51 to $100 (51%), $101 to $150 (20%), and >$150 (10%). Forty-two percent of programs covered the cost of vitamin D supplements. More than half of the participants indicated that vitamin D blood testing and supplements were not a good use of program funds. In comparison with Football Championship Subdivision programs, Football Bowl Subdivision programs were more likely to conduct vitamin D testing and pay for vitamin D supplements, and their providers were more likely to believe that testing and supplements were a good use of program funds. CONCLUSIONS: A great deal of variability was present in vitamin D-related clinical practices among NCAA Division I athletics programs, which reflects existing contradictions and uncertainty in research, recommendations, and guidelines. Knowledge of current practice patterns is important in evaluating and establishing best practices, policies, and procedures for sports medicine and sports nutrition professionals in the collegiate setting.

Heat stress decreases metabolic flexibility in skeletal muscle of growing pigs.

Heat-stressed pigs experience metabolic alterations, including altered insulin profiles, reduced lipid mobilization, and compromised intestinal integrity. This is bioenergetically distinct from thermal neutral pigs on a similar nutritional plane. To delineate differences in substrate preferences between direct and indirect (via reduced feed intake) heat stress effects, skeletal muscle fuel metabolism was assessed. Pigs (35.3 ± 0.8 kg) were randomly assigned to three treatments: thermal neutral fed ad libitum (TN; 21°C, n = 8), heat stress fed ad libitum (HS; 35°C, n = 8), and TN, pair-fed/HS intake (PF; n = 8) for 7 days. Body temperature (TB) and feed intake (FI) were recorded daily. Longissimus dorsi muscle was biopsied for metabolic assays on days -2, 3, and 7 relative to initiation of environmental treatments. Heat stress increased TB and decreased FI ( P < 0.05). Heat stress inhibited incomplete fatty acid oxidation and glucose oxidation ( P < 0.05). Metabolic flexibility decreased in HS pigs compared with TN and PF controls ( P < 0.05). Both phosphofructokinase and pyruvate dehydrogenase (PDH) activities increased in PF ( P < 0.05); however, TN and HS did not differ. Heat stress inhibited citrate synthase and ß-hydroxyacyl-CoA dehydrogenase (ß-HAD) activities ( P < 0.05). Heat stress did not alter PDH phosphorylation or carnitine palmitoyltransferase 1 abundance but reduced acetyl-CoA carboxylase 1 (ACC1) protein abundance ( P < 0.05). In conclusion, HS decreased skeletal muscle fatty acid oxidation and metabolic flexibility, likely involving ß-HAD and ACC regulation.

Inulin Supplementation Does Not Reduce Plasma Trimethylamine N-Oxide Concentrations in Individuals at Risk for Type 2 Diabetes.

Trimethylamine N-oxide (TMAO) is associated with type 2 diabetes (T2DM) and increased risk of adverse cardiovascular events. Prebiotic supplementation has been purported to reduce TMAO production, but whether prebiotics reduce fasting or postprandial TMAO levels is unclear. Sedentary, overweight/obese adults at risk for T2DM (n = 18) were randomized to consume a standardized diet (55% carbohydrate, 30% fat) with 10 g/day of either an inulin supplement or maltodextrin placebo for 6 weeks. Blood samples were obtained in the fasting state and hourly during a 4-h high-fat challenge meal (820 kcal; 25% carbohydrate, 63% fat; 317.4 mg choline, 62.5 mg betaine, 8.1 mg l-carnitine) before and after the diet. Plasma TMAO and trimethylamine (TMA) moieties (choline, l-carnitine, betaine, and γ-butyrobetaine) were measured using isocratic ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). There were no differences in fasting or postprandial TMAO or TMA moieties between the inulin and placebo groups at baseline (all p > 0.05). There were no significant changes in fasting or postprandial plasma TMAO or TMA moiety concentrations following inulin or placebo. These findings suggest that inulin supplementation for 6 weeks did not reduce fasting or postprandial TMAO in individuals at risk for T2DM. Future studies are needed to identify efficacious interventions that reduce plasma TMAO concentrations.

Alterations to metabolically active bacteria in the mucosa of the small intestine predict anti-obesity and anti-diabetic activities of grape seed extract in mice.

Epidemiological and clinical studies suggest that grapes and grape-derived products may reduce the risk for chronic disease. Grape seed extract specifically has been gaining interest due to its reported ability to prevent weight gain, moderate hyperglycemia, and reduce inflammation. The purpose of this study was to examine the long-term effects of two doses of grape seed extract (10 and 100 mg kg-1 body wt per d in mice) on markers of metabolic syndrome in the context of a moderately high-fat diet. After 12 weeks, the lower dose of grape seed extract was more effective at inhibiting fat gain and improving glucose tolerance and insulin sensitivity. Neither the high fat diet nor grape seed extract altered skeletal muscle substrate metabolism. Most interestingly, when examining the profile of metabolically active microbiota in the mucosa of the small intestine, cecum, and colonic tissue, grape seed extract seemed to have the most dramatic effect on small intestinal tissue, where the population of Firmicutes was lower compared to control groups. This effect was not observed in the cecal or colonic tissues, suggesting that the main alterations to gut microbiota due to flavan-3-ol supplementation occur in the small intestine, which has not been reported previously. These findings suggest that grape seed extract can prevent early changes in glucose tolerance and alter small intestinal gut microbiota, prior to the onset of skeletal muscle metabolic derangements, when grape seed extract is consumed at a low dose in the context of a moderately high fat diet.

High-molecular-weight cocoa procyanidins possess enhanced insulin-enhancing and insulin mimetic activities in human primary skeletal muscle cells compared to smaller procyanidins.

Dysregulation of glucose metabolism is a primary hallmark of metabolic disease (i.e., diabetes, obesity, etc.). Complementary nonpharmaceutical strategies are needed to prevent and/or ameliorate dysregulation of glucose metabolism and prevent progression from normoglycemia to prediabetes and type 2 diabetes across the lifespan. Cocoa compounds, particularly the procyanidins, have shown promise for improving insulin sensitivity and blood glucose homeostasis. However, the molecular mechanisms by which cocoa procyanidins exert these functions remain poorly understood. Furthermore, cocoa procyanidins exhibit size diversity, and evidence suggests that procyanidin bioactivity and size may be related. Here, we show that a procyanidin-rich cocoa extract elicits an antidiabetic effect by stimulating glycogen synthesis and glucose uptake, independent of insulin. Cocoa procyanidins did not appear to act via stimulation of AMPK or CaMKII activities. Additionally, in the presence of insulin, glycogen synthesis and AKT phosphorylation were affected. These mechanisms of action are most pronounced in response to oligomeric and polymeric procyanidins. These results demonstrate (1) specific mechanisms by which cocoa procyanidins improve glucose utilization in skeletal muscle and (2) that larger procyanidins appear to possess enhanced activities. These mechanistic insights suggest specific strategies and biological contexts that may be exploited to maximize the antidiabetic benefits of cocoa procyanidins.

Mechanisms by which cocoa flavanols improve metabolic syndrome and related disorders.

Dietary administration of cocoa flavanols may be an effective complementary strategy for alleviation or prevention of metabolic syndrome, particularly glucose intolerance. The complex flavanol composition of cocoa provides the ability to interact with a variety of molecules, thus allowing numerous opportunities to ameliorate metabolic diseases. These interactions likely occur primarily in the gastrointestinal tract, where native cocoa flavanol concentration is high. Flavanols may antagonize digestive enzymes and glucose transporters, causing a reduction in glucose excursion, which helps patients with metabolic disorders maintain glucose homeostasis. Unabsorbed flavanols, and ones that undergo enterohepatic recycling, will proceed to the colon where they can exert prebiotic effects on the gut microbiota. Interactions with the gut microbiota may improve gut barrier function, resulting in attenuated endotoxin absorption. Cocoa may also positively influence insulin signaling, possibly by relieving insulin-signaling pathways from oxidative stress and inflammation and/or via a heightened incretin response. The purpose of this review is to explore the mechanisms that underlie these outcomes, critically review the current body of literature related to those mechanisms, explore the implications of these mechanisms for therapeutic utility, and identify emerging or needed areas of research that could advance our understanding of the mechanisms of action and therapeutic potential of cocoa flavanols.

Probiotic supplementation and trimethylamine-N-oxide production following a high-fat diet.

OBJECTIVE: The objective of this study was to test the hypothesis that the multi-strain probiotic VSL#3 would attenuate the increase in fasting plasma concentrations of trimethylamine-N-oxide (TMAO) following a high-fat diet. METHODS: Nineteen healthy, non-obese males (18-30 years) participated in the present study. Following a 2-week eucaloric control diet, subjects were randomized to either VSL#3 (900 billion live bacteria) or placebo (cornstarch) during the consumption of a hypercaloric (+1,000 kcal day(-1) ), high-fat diet (55% fat) for 4 weeks. Plasma TMAO, L-carnitine, choline, and betaine (UPLC-MS/MS) were measured at baseline and following a high-fat diet. RESULTS: Plasma TMAO significantly increased 89% ± 66% vs. 115% ± 61% in both the VSL#3 and placebo groups, respectively; however, the magnitude of change in plasma TMAO was not different (P > 0.05) between them. Plasma L-carnitine, choline, and betaine concentrations did not increase following the high-fat diet in either group. CONCLUSIONS: A high-fat diet increases plasma TMAO in healthy, normal-weight, young males. However, VSL#3 treatment does not appear to influence plasma TMAO concentrations following a high-fat diet. Future studies are needed to determine whether other therapeutic strategies can attenuate the production of TMAO.

Probiotic supplementation attenuates increases in body mass and fat mass during high-fat diet in healthy young adults.

OBJECTIVE: The objective was to determine the effects of the probiotic, VSL#3, on body and fat mass, insulin sensitivity, and skeletal muscle substrate oxidation following 4 weeks of a high-fat diet. METHODS: Twenty non-obese males (18-30 years) participated in the study. Following a 2-week eucaloric control diet, participants underwent dual X-ray absorptiometry to determine body composition, an intravenous glucose tolerance test to determine insulin sensitivity, and a skeletal muscle biopsy for measurement of in vitro substrate oxidation. Subsequently, participants were randomized to receive either VSL#3 or placebo daily during 4 weeks of consuming a High-fat (55% fat), hypercaloric diet (+1,000 kcal day(-1) ). Participants repeated all measurements following the intervention. RESULTS: Body mass (1.42 ± 0.42 kg vs. 2.30 ± 0.28 kg) and fat mass (0.63 ± 0.09 kg vs. 1.29 ± 0.27 kg) increased less following the High-fat diet in the VSL#3 group compared with placebo. However, there were no significant changes in insulin sensitivity or in vitro skeletal muscle pyruvate and fat oxidation with the High-fat diet or VSL#3. CONCLUSIONS: VSL#3 supplementation appears to have provided some protection from body mass gain and fat accumulation in healthy young men consuming a High-fat and high-energy diet.

Dietary supplementation with cocoa flavanols does not alter colon tissue profiles of native flavanols and their microbial metabolites established during habitual dietary exposure in C57BL/6J mice.

Metabolism of flavanols (catechins, procyanidins) by gut microbiota has been extensively characterized. Comparatively little is known about accumulation of flavanols and their metabolites in the colon tissues, particularly during chronic exposure to low doses. Mice were fed low doses of cocoa flavanols for 12 weeks. Supplementation of the control diet with flavanols did not increase colonic tissue accumulation of flavanols nor microbial metabolites versus control. The type of cocoa flavanols did not affect colonic tissue accumulation of native flavanols or metabolites. Total phenolic content of the diets indicated that these results are not explained by background levels of undetected phenolics in the control diet. This is the longest known chronic flavanol feeding study to examine colonic tissue accumulation. Vast differences appear to exist between acute high doses and chronic low doses, to which gut microbiota and epithelium adapt. These results indicate that the fate of flavanols in the colon during chronic exposure is not fully understood.

Dietary supplementation of chinese ginseng prevents obesity and metabolic syndrome in high-fat diet-fed mice.

Obesity and diabetes are growing health problems worldwide. In this study, dietary provision of Chinese ginseng (0.5 g/kg diet) prevented body weight gain in high-fat (HF) diet-fed mice. Dietary ginseng supplementation reduced body fat mass gain, improved glucose tolerance and whole body insulin sensitivity, and prevented hypertension in HF diet-induced obese mice. Ginseng consumption led to reduced concentrations of plasma insulin and leptin, but had no effect on plasma adiponectin levels in HF diet-fed mice. Body temperature was higher in mice fed the ginseng-supplemented diet but energy expenditure, respiration rate, and locomotive activity were not significantly altered. Dietary intake of ginseng increased fatty acid oxidation in the liver but not in skeletal muscle. Expression of several transcription factors associated with adipogenesis (C/EBPα and PPARγ) were decreased in the adipose tissue of HF diet-fed mice, effects that were mitigated in mice that consumed the HF diet supplemented with ginseng. Abundance of fatty acid synthase (FASN) mRNA was greater in the adipose tissue of mice that consumed the ginseng-supplemented HF diet as compared with control or un-supplemented HF diet-fed mice. Ginseng treatment had no effect on the expression of genes involved in the regulation of food intake in the hypothalamus. These data suggest that Chinese ginseng can potently prevent the development of obesity and insulin resistance in HF diet-fed mice.

Oligomeric cocoa procyanidins possess enhanced bioactivity compared to monomeric and polymeric cocoa procyanidins for preventing the development of obesity, insulin resistance, and impaired glucose tolerance during high-fat feeding.

There is interest in the potential of cocoa flavanols, including monomers and procyanidins, to prevent obesity and type-2 diabetes. Fermentation and processing of cocoa beans influence the qualitative and quantitative profiles of individual cocoa constituents. Little is known regarding how different cocoa flavanols contribute to inhibition of obesity and type-2 diabetes. The objective of this study was to compare the impacts of long-term dietary exposure to cocoa flavanol monomers, oligomers, and polymers on the effects of high-fat feeding. Mice were fed a high-fat diet supplemented with either a cocoa flavanol extract or a flavanol fraction enriched with monomeric, oligomeric, or polymeric procyanidins for 12 weeks. The oligomer-rich fraction proved to be most effective in preventing weight gain, fat mass, impaired glucose tolerance, and insulin resistance in this model. This is the first long-term feeding study to examine the relative activities of cocoa constituents on diet-induced obesity and insulin resistance.

Chronic administration of dietary grape seed extract increases colonic expression of gut tight junction protein occludin and reduces fecal calprotectin: a secondary analysis of healthy Wistar Furth rats.

Animal studies have demonstrated the potential of grape seed extract (GSE) to prevent metabolic syndrome, obesity, and type 2 diabetes. Recently, metabolic endotoxemia induced by bacterial endotoxins produced in the colon has emerged as a possible factor in the etiology of metabolic syndrome. Improving colonic barrier function may control endotoxemia by reducing endotoxin uptake. However, the impact of GSE on colonic barrier integrity and endotoxin uptake has not been evaluated. We performed a secondary analysis of samples collected from a chronic GSE feeding study with pharmacokinetic end points to examine potential modulation of biomarkers of colonic integrity and endotoxin uptake. We hypothesized that a secondary analysis would indicate that chronic GSE administration increases colonic expression of intestinal tight junction proteins and reduces circulating endotoxin levels, even in the absence of an obesity-promoting stimulus. Wistar Furth rats were administered drinking water containing 0.1% GSE for 21 days. Grape seed extract significantly increased the expression of gut junction protein occludin in the proximal colon and reduced fecal levels of the neutrophil protein calprotectin, compared with control. Grape seed extract did not significantly reduce serum or fecal endotoxin levels compared with control, although the variability in serum levels was widely increased by GSE. These data suggest that the improvement of gut barrier integrity and potential modulation of endotoxemia warrant investigation as a possible mechanism by which GSE prevents metabolic syndrome and associated diseases. Further investigation of this mechanism in high-fat feeding metabolic syndrome and obesity models is therefore justified.

Endurance capacity in maturing mdx mice is markedly enhanced by combined voluntary wheel running and green tea extract.

Duchenne muscular dystrophy is characterized by the absence of dystrophin from muscle cells. Dystrophic muscle cells are susceptible to oxidative stress. We tested the hypothesis that 3 wk of endurance exercise starting at age 21 days in young male mdx mice would blunt oxidative stress and improve dystrophic skeletal muscle function, and these effects would be enhanced by the antioxidant green tea extract (GTE). In mice fed normal diet, average daily running distance increased 300% from week 1 to week 3, and total distance over 3 wk was improved by 128% in mice fed GTE. Running, independent of diet, increased serum antioxidant capacity, extensor digitorum longus tetanic stress, and total contractile protein content, heart citrate synthase, and heart and quadriceps beta-hydroxyacyl-CoA dehydrogenase activities. GTE, independent of running, decreased serum creatine kinase and heart and gastrocnemius lipid peroxidation and increased gastrocnemius citrate synthase activity. These data suggest that both endurance exercise and GTE may be beneficial as therapeutic strategies to improve muscle function in mdx mice.

Role of adiponectin in human skeletal muscle bioenergetics.

Insulin resistance is associated with impaired skeletal muscle oxidation capacity and reduced mitochondrial number and function. Here, we report that adiponectin signaling regulates mitochondrial bioenergetics in skeletal muscle. Individuals with a family history of type 2 diabetes display skeletal muscle insulin resistance and mitochondrial dysfunction; adiponectin levels strongly correlate with mtDNA content. Knockout of the adiponectin gene in mice is associated with insulin resistance and low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle. Adiponectin treatment of human myotubes in primary culture induces mitochondrial biogenesis, palmitate oxidation, and citrate synthase activity, and reduces the production of reactive oxygen species. The inhibition of adiponectin receptor expression by siRNA, or of AMPK by a pharmacological agent, blunts adiponectin induction of mitochondrial function. Our findings define a skeletal muscle pathway by which adiponectin increases mitochondrial number and function and exerts antidiabetic effects.

Chromium picolinate enhances skeletal muscle cellular insulin signaling in vivo in obese, insulin-resistant JCR:LA-cp rats.

Chromium is one of the few trace minerals for which a specific cellular mechanism of action has not been identified. Recent in vitro studies suggest that chromium supplementation may improve insulin sensitivity by enhancing insulin receptor signaling, but this has not been demonstrated in vivo. We investigated the effect of chromium supplementation on insulin receptor signaling in an insulin-resistant rat model, the JCR:LA-corpulent rat. Male JCR:LA-cp rats (4 mo of age) were randomly assigned to receive chromium picolinate (CrPic) (obese n=6, lean n=5) or vehicle (obese n=5, lean n=5) for 3 mo. The CrPic was provided in the water, and based on calculated water intake, rats randomized to CrPic received 80 microg/(kg.d). At the end of the study, skeletal muscle (vastus lateralis) biopsies were obtained at baseline and at 5, 15, and 30 min postinsulin stimulation to assess insulin signaling. Obese rats treated with CrPic had significantly improved glucose disposal rates and demonstrated a significant increase in insulin-stimulated phosphorylation of insulin receptor substrate (IRS)-1 and phosphatidylinositol (PI)-3 kinase activity in skeletal muscle compared with obese controls. The increase in cellular signaling was not associated with increased protein levels of the IRS proteins, PI-3 kinase or Akt. However, protein tyrosine phosphatase 1B (PTP1B) levels were significantly lower in obese rats administered CrPic than obese controls. When corrected for protein content, PTP1B activity was also significantly lower in obese rats administered CrPic than obese controls. Our data suggest that chromium supplementation of obese, insulin-resistant rats may improve insulin action by enhancing intracellular signaling.

Pinitol supplementation does not affect insulin-mediated glucose metabolism and muscle insulin receptor content and phosphorylation in older humans.

This study assessed the effect of oral pinitol supplementation on oral and intravenous glucose tolerances and on skeletal muscle insulin receptor content and phosphorylation in older people. Fifteen people (6 men, 9 women; age 66 +/- 8 y; BMI 27.9 +/- 3.3 kg/m(2); hemoglobin A1c 5.39 +/- 0.46%, mean +/- SD) completed a 7-wk protocol. Subjects were randomly assigned to groups that during wk 2-7 consumed twice daily either a non-nutritive beverage (Placebo group, n = 8) or the same beverage with 1000 mg pinitol dissolved into it (Pinitol group, n = 7, total dose = 2000 mg pinitol/d). Testing was done at wk 1 and wk 7. In the Pinitol group with supplementation, 24-h urinary pinitol excretion increased 17-fold. The fasting concentrations of glucose, insulin, and C-peptide, and the 180-min area under the curve for these compounds, in response to oral (75 g) and intravenous (300 mg/kg) glucose tolerance challenges, were unchanged from wk 1 to wk 7 and were not influenced by pinitol. Also, pinitol did not affect indices of hepatic and whole-body insulin sensitivity from the oral glucose tolerance test and indices of insulin sensitivity, acute insulin response to glucose, and glucose effectiveness from the intravenous glucose tolerance test, estimated using minimal modeling. Pinitol did not differentially affect total insulin receptor content and insulin receptor phosphotyrosine 1158 and insulin receptor phosphotyrosine 1162/1163 activation in vastus lateralis samples taken during an oral-glucose-induced hyperglycemic and hyperinsulinemic state. These data suggest that pinitol supplementation does not influence whole-body insulin-mediated glucose metabolism and muscle insulin receptor content and phosphorylation in nondiabetic, older people.

Effects of liquid carbohydrate ingestion on markers of anabolism following high-intensity resistance exercise.

We examined the effects of liquid carbohydrate (CHO) supplementation on markers of anabolism following high-intensity resistance exercise. Nine resistance-trained men consumed either CHO or placebo (PLC) 10 minutes before and immediately following 2 resistance exercise sessions. Cortisol (CORT), insulin (INS), ammonia (AMM), and glucose (GLU) were measured before, immediately after, and 1.5 and 4 hours after exercise. Urinary nitrogen (NH(+3)) was measured 24 hours before and after exercise. There was a significant difference in INS levels immediately after exercise and 1.5 hours after exercise. No significant differences were observed for CORT, AMM, GLU, or NH(+3)between treatments. Significant within-group differences were found for the PLC group: CORT before compared with immediately after exercise; INS before compared with immediately after exercise and before compared with 1.5 hours after exercise; and AMM before compared with immediately after exercise and before compared with 1.5 hours after exercise. Significant within-group differences were found for the CHO group: CORT immediately after compared with 1.5 hours after exercise and immediately after compared with 4 hours after exercise; INS before compared with 1.5 hours after exercise; and AMM before compared with immediately after exercise. Liquid CHO ingestion leads to a more favorable anabolic environment immediately following a resistance exercise bout; however, our indirect measures of protein degradation were not altered by CHO ingestion.