Insulinotropic and Muscle Protein Synthetic Effects of Branched-Chain Amino Acids: Potential Therapy for Type 2 Diabetes and Sarcopenia

Manders, Ralph; Little, Jonathan P.; Forbes, Scott C.; Candow, Darren G.

doi:10.3390/nu4111664

Cited by 63 publications

(55 citation statements)

References 102 publications

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“…Volek et al (2013) provides evidence that humans fed protein (e.g., whey protein) containing a higher proportion of leucine will result in an elevation of blood leucine concentration and stimulate muscle protein synthesis and this may lead to greater gains in muscle mass over time; however, others do not support this linear association between elevated leucine and enhanced muscle protein synthesis (Churchward-Venne et al, 2012). In addition, changes in muscle protein synthesis are relatively small unless sufficient EAA are provided (Manders et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Elevated extracellular aminoacidemia following whey protein ingestion is known to enhance skeletal muscle myofibrillar protein synthesis (Bohe et al, 2003;West et al, 2011) which is stimulated primarily by EAAs (Paddon-Jones et al, 2004;Tipton et al, 1999;Volpi et al, 2003) and by the BCAA leucine (Drummond and Rasmussen, 2008). Intravenous administration of BCAAs elevates the phosphorylation and activation of p70S6 kinase and 4E-BP1 (Greiwe et al, 2001); p70S6 kinase and 4E-BP1 which are downstream substrates of the mammalian target of rapamycin (mTOR) pathway (Greiwe et al, 2001;Liu et al, 2006;Manders et al, 2012). Leucine supplementation alone has been shown to directly phosphorylate and activate mTOR (Fujita et al, 2007); however, alterations in the rates of myofibrillar protein synthesis are relatively transient unless EAA are provided in sufficient quantities (Manders et al, 2012).…”

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confidence: 99%

“…Intravenous administration of BCAAs elevates the phosphorylation and activation of p70S6 kinase and 4E-BP1 (Greiwe et al, 2001); p70S6 kinase and 4E-BP1 which are downstream substrates of the mammalian target of rapamycin (mTOR) pathway (Greiwe et al, 2001;Liu et al, 2006;Manders et al, 2012). Leucine supplementation alone has been shown to directly phosphorylate and activate mTOR (Fujita et al, 2007); however, alterations in the rates of myofibrillar protein synthesis are relatively transient unless EAA are provided in sufficient quantities (Manders et al, 2012). Furthermore, Calbet and MacLean (2002) found that whey protein produced a significant increase in circulating levels of insulin and this insulin response was greater than achieved with a carbohydrate solution.…”

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confidence: 99%

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Dose Response of Whey Protein Isolate in Addition to a Typical Mixed Meal on Blood Amino Acids and Hormonal Concentrations

Forbes

McCargar²,

Jelen³

et al. 2014

International Journal of Sport Nutrition and Exercise Metabolism

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The purpose was to investigate the effects of a controlled typical 1-day diet supplemented with two different doses of whey protein isolate on blood amino acid profiles and hormonal concentrations following the final meal. Nine males (age: 29.6 ± 6.3 yrs) completed four conditions in random order: a control (C) condition of a typical mixed diet containing ~10% protein (0.8 g·kg1), 65% carbohydrate, and 25% fat; a placebo (P) condition calorically matched with carbohydrate to the whey protein conditions; a low-dose condition of 0.8 grams of whey protein isolate per kilogram body mass per day (g·kg1·d1; W1) in addition to the typical mixed diet; or a high-dose condition of 1.6 g·kg1·d1 (W2) of supplemental whey protein in addition to the typical mixed diet. Following the final meal, significant (p < .05) increases in total amino acids, essential amino acids (EAA), branch-chained amino acids (BCAA), and leucine were observed in plasma with whey protein supplementation while no changes were observed in the control and placebo conditions. There was no significant group difference for glucose, insulin, testosterone, cortisol, or growth hormone. In conclusion, supplementing a typical daily food intake consisting of 0.8 g of protein·kg1·d1 with a whey protein isolate (an additional 0.8 or 1.6 g·kg1·d1) significantly elevated total amino acids, EAA, BCAA, and leucine but had no effect on glucose, insulin, testosterone, cortisol, or growth hormone following the final meal. Future acute and chronic supplementation research examining the physiological and health outcomes associated with elevated amino acid profiles is warranted.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Dose Response of Whey Protein Isolate in Addition to a Typical Mixed Meal on Blood Amino Acids and Hormonal Concentrations

Forbes

McCargar²,

Jelen³

et al. 2014

International Journal of Sport Nutrition and Exercise Metabolism

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“…Although a large body of observational studies have examined dietary fat and carbohydrate affecting T2D risk4, relatively few studies have directly investigated the role of dietary protein in relation to T2D risk. Short–term intervention studies have revealed that protein intake positively affects body weight control and promotes insulin secretion in pancreatic β-cells5678. In contrast, large and long-term observational studies generally pointed in the opposite direction relating the effect of protein intake to insulin sensitivity and T2D risk9101112.…”

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confidence: 99%

Dietary Protein Intake and Type 2 Diabetes Among Women and Men in Northeast China

Sun

Liu

et al. 2016

Sci Rep

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We conducted a comprehensive and in-depth assessment of different dietary protein sources related to type 2 diabetes (T2D) and determined whether the association is mediated by insulin resistance (IR) and β-cell dysfunction in a population-based cross sectional study of 4,427 women and 2,394 men aged 20–74 years in northeast China. We observed that the intake of total protein, animal protein, and red meat protein was positively associated with T2D prevalence in women. Comparing the women in the highest quintile of protein intake with those in the lowest quintile, the multivariable-adjusted odds ratios of T2D were 2.13 [95% confidence interval (CI): 1.18–3.81] for total protein, 2.27 (95% CI: 1.18–4.35) for animal protein, and 1.75 (95% CI: 1.14–2.68) for red meat protein. Mediation analyses indicated that these associations were mediated mainly by the IR as measured by the homeostasis model (HOMA-IR). The proportions via the mediation of HOMA-IR were 29.0% (95% CI: 10.3%–55.5%), 35.0% (95% CI: 12.9%–83.3%), and 17.2% (95% CI: 5.2%–44.8%) for total protein-, animal protein-, and red meat protein–T2D associations, respectively. These findings support the notion that modifying the sources of dietary protein may be potentially applied to prevent T2D.

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“…One of the mechanisms of protein-induced insulin resistance appears to be inhibition of glucose uptake through phosphorylation of downstream factors of the insulin signaling cascade by the translation initiation factor serine-kinase-6-1 (S6K1) (Tremblay et al, 2005). On the other hand, it has been put forward that branched-chain amino acids (BCAA), in particular leucine, may help to counteract "anabolic" resistance" which may increase availability of AA for muscle protein synthesis, 568 reduce muscle protein breakdown, and enhance glucose disposal to help maintain blood glucose homeostasis in T2DM (Manders et al, 2012). Recent data on metabolomic profiling in obese adults have suggested associations between BCAA and future risk of T2DM (Newgard et al, 2009a(Newgard et al, , 2009b, whereas the opposite has been found in youth (Michaliszyn et al, 2012a(Michaliszyn et al, , 2012b.…”

Section: Dietary Protein and Blood Glucose Regulationmentioning

confidence: 99%

Impact of Diet Composition on Blood Glucose Regulation

Russell

Baka

Björck

et al. 2013

Critical Reviews in Food Science and Nutrition

191

121

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Nutritional management of blood glucose levels is a strategic target in the prevention and management of type 2 diabetes mellitus (T2DM). To implement such an approach, it is essential to understand the effect of food on glycemic regulation and on the underlying metabolic derangements. This comprehensive review summarizes the results from human dietary interventions exploring the impact of dietary components on blood glucose levels. Included are the major macronutrients; carbohydrate, protein and fat, micronutrient vitamins and minerals, nonnutrient phytochemicals and additional foods including low-calorie sweeteners, vinegar, and alcohol. Based on the evidence presented in this review, it is clear that dietary components have significant and clinically relevant effects on blood glucose modulation. An integrated approach that includes reducing excess body weight, increased physical activity along with a dietary regime to regulate blood glucose levels will not only be advantages in T2DM management, but will benefit the health of the population and limit the increasing worldwide incidence of T2DM.

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Insulinotropic and Muscle Protein Synthetic Effects of Branched-Chain Amino Acids: Potential Therapy for Type 2 Diabetes and Sarcopenia

Cited by 63 publications

References 102 publications

Dose Response of Whey Protein Isolate in Addition to a Typical Mixed Meal on Blood Amino Acids and Hormonal Concentrations

Dose Response of Whey Protein Isolate in Addition to a Typical Mixed Meal on Blood Amino Acids and Hormonal Concentrations

Dietary Protein Intake and Type 2 Diabetes Among Women and Men in Northeast China

Impact of Diet Composition on Blood Glucose Regulation

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