Browsing by Subject "Leucine"
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Item Activation of skeletal muscle glucose uptake by am [i.e. an] amino acid mixture and its impact on glucose tolerance and insulin resistance(2011-08) Bernard, Jeffrey Richard; Ivy, John, 1945-; Farrar, Roger P.; Tanaka, Hirofumi; Hursting, Stephen D.; Nunez, Nomeli P.Recent research suggests that amino acids can significantly increase skeletal muscle glucose uptake. However, the mechanism(s) have not been fully elucidated and it is also not clear if the beneficial impact amino acids have on healthy tissue translates to insulin resistant skeletal muscle. Therefore, in this series of studies, the effects of an amino acid mixture on glucose tolerance and insulin resistance were investigated. Study 1 Experiment-1 (Exp-1) demonstrated that an amino acid mixture significantly reduced the blood glucose response to an oral glucose challenge in Sprague Dawley rats. In Study 1 Exp-2, it was found that the improved glucose tolerance was due to an increase in skeletal muscle glucose uptake. The enhanced amino acid induced muscle glucose uptake was associated with improved cellular signaling. In Study 1 we could not determine the combined and/or individual effects of insulin and amino acids on glucose uptake, so in Study 2, the hindlimb of Sprague Dawley rats were perfused with glucose with or without amino acids in the presence and absence of insulin. Study 2, confirmed our previous findings that an amino acid mixture increased skeletal muscle glucose uptake compared to a carbohydrate supplement in the presence of insulin. The enhanced amino acid-stimulated glucose uptake was not due to increased phosphatidylinositol 3-kinase (PI 3-kinase) activity, although it was related to an increase in Akt substrate of 160 kDa (AS160) phosphorylation and a greater number of glucose transporters at the plasma membrane. In the final experiment, Study 3 investigated whether amino acids could improve glucose tolerance in an insulin resistant model. Study 3 Exp-1, demonstrated that an amino acid mixture significantly lowered the blood glucose response to an oral glucose challenge in obese Zucker rats. Study 3 Exp-2 showed that the improved glucose tolerance was due to enhanced amino acid induced skeletal muscle glucose uptake. Taken together, the results of this research suggests that adding an amino acid mixture to a carbohydrate supplement improves the blood glucose response to an oral glucose challenge, acutely lowers insulin resistance and this appears due to increased skeletal muscle glucose clearance and enhanced cellular signaling.Item The effectiveness of protein, leucine and [beta]-hydroxy-[beta]-methylbutyrate on cell-signaling pathways controlling protein turnover in red and white gastrocnemius muscles of rats(2011-08) Wang, Wanyi, M.S. in Kinesiology; Ivy, John, 1945-; Farrar, Roger P.Whey protein supplementation, containing large amount of leucine, has been a traditional intervention to maintain net protein balance in the past decades. It has been recognized that leucine alone is able to stimulate protein synthesis by activating mTOR and its related downstream pathway without affecting protein degradation, whereas its metabolite β-hydroxy-β-methylbutyrate (HMB) is known to attenuate protein degradation when provided chronically. However, the mechanism of HMB’s benefit remains unclear. To address how HMB regulates protein synthesis and degradation signaling pathways, we compared one dose of whey protein (187.5mg/kg), HMB (400mg/kg) or leucine (1.4g/kg) by oral gavage. Blood was collected at 0, 45 and 90 min for blood glucose and plasma insulin analysis. Red and white gastrocnemius muscle was taken separately 90 min after gavage. Blood glucose was reduced by leucine at 45 and 90 min post gavage. Plasma insulin was enhanced by leucine at 45 min and then decreased at 90 min post gavage, whereas HMB decreased plasma insulin through 90 min post gavege. Western blot analysis showed that HMB phosphorylated Akt in red gastronemius, and enhanced phosphorylation of mTOR in both types of muscles. Leucine phosphorylated mTOR, p70s6k and 4E-BP1 in both red and white gastronemius. Regarding protein degradation signals, phosphorylation of FOXO3A was enhanced by HMB, but not in the other treatment groups. Whey protein had no effect on those cellular signaling. Our results indicate that both HMB and leucine may stimulate protein synthesis through the mTOR pathway in red and white gastrocnemius muscles by different degrees with leucine more effective than HMB. HMB may have a greater effect than leucine on limiting protein degradation by phosphorylating Akt and FOXO3A in red and white gastrocnemius muscles. A combination of HMB and leucine, as a new interventional strategy, is predicted to maximize protein accretion by increasing protein synthesis as well as inhibiting protein degradation.Item The effects of carbohydrate and HMB supplementation on glycogen synthesis post-exercise(2013-08) Choi, Ran Hee; Farrar, Roger P.Carbohydrate plus additional protein supplementation provided immediately after exercise has been found to increase the rate of muscle glycogen restoration compared to carbohydrate alone. To examine whether leucine, and/or β-hydroxy-β-methylbutyrate (HMB) to carbohydrate plus protein supplementation affects short-term recovery (45 min) of muscle glycogen, we compared plasma glucose and insulin, the muscle glycogen concentration, and the cellular signaling proteins controlling muscle glycogen synthesis 45 min after supplementation. Rats (n=35) underwent high-intensity resistance exercise followed by supplementation with carbohydrate (CHO: 1.2g/kg body weight), carbohydrate with whey protein (CP: 1.2g CHO + 375mg whey protein/kg body weight), carbohydrate with whey protein plus HMB (CPH: 1.2g CHO + 375mg whey protein + 400mg HMB/kg body weight), carbohydrate with whey protein, HMB plus leucine (CPHL: 1.2g CHO + 375mg whey protein + 400mg HMB + 444mg leucine/kg body weight) or exercise only (CON). Blood samples were collected immediately after exercise and 45 min after supplementations. Muscle samples of plantaris were excised immediately and 45 min post-exercise. Plasma glucose was increased by CHO and CPH supplementation and reduced by CPHL at 45 min post-exercise. Plasma insulin was elevated by CP and CPHL treatments compare to CHO. Muscle glycogen concentration was unaffected by all treatments and did not differ from CON. Phosphorylation of Akt/PKB, GSK3α/β, and GS at 45 min of recovery for all supplements was not significant difference from CON. Phosphorylation of mTOR was significantly increased by CPHL and CP supplementation compared to CON, CHO, and CPH. Phosphorylation of AS160 was markedly reduced by CPH supplementation compared to CON. These results suggest that supplementing with carbohydrate plus protein with or without leucine and its metabolite, HMB, to enhance muscle glycogen replenishment following exercise may not provide an advantage during the early phase of recovery (45 min). Furthermore, there is some indication that HMB may elicit insulin resistance, and this needs further evaluation.