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An amino acid mixture improves glucose tolerance and lowers insulin resistance in the obese Zucker rat

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Abstract

The purpose of this investigation was to test an amino acid mixture on glucose tolerance in obese Zucker rats [experiment (Exp)-1] and determine whether differences in blood glucose were associated with alterations in muscle glucose uptake [experiment (Exp)-2]. Exp-1 rats were gavaged with either carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1), carbohydrate plus amino acid mixture with increased leucine concentration (OB-AA-2) or water (OB-PLA). The glucose response in OB-AA-1 and OB-AA-2 were similar, and both were lower compared to OB-CHO. This effect of the amino acid mixtures did not appear to be solely attributable to an increase in plasma insulin. Rats in Exp-2 were gavaged with carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1) or water (OB-PLA). Lean Zuckers were gavaged with carbohydrate (LN-CHO). Fifteen minutes after gavage, a radiolabeled glucose analog was infused through a catheter previously implanted in the right jugular vein. Blood glucose was significantly lower in OB-AA-1 compared to OB-CHO while the insulin responses were similar. Glucose uptake was greater in OB-AA-1 compared with OB-CHO, and similar to that in LN-CHO in red gastrocnemius muscle (5.15 ± 0.29, 3.8 ± 0.27, 5.18 ± 0.34 µmol/100 g/min, respectively). Western blot analysis showed that Akt substrate of 160 kDa (AS160) phosphorylation was enhanced for OB-AA-1 and LN-CHO compared to OB-CHO. These findings suggest that an amino acid mixture improves glucose tolerance in an insulin resistant model and that these improvements are associated with an increase in skeletal muscle glucose uptake possibly due to improved intracellular signaling.

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Acknowledgments

The authors would like to thank Dr. Martin Job and Dr. Simon Schenk for their assistance in preparing our lab for the jugular vein catheterization procedure. We would also like to thank Lynne Kammer and Mina Rathbun for their excellent technical assistance.

Conflict of interest

  This research was support by a grant from Abbott Nutrition, Abbott Laboratories, Columbus, Ohio. Dr. Jeffrey Nelson is an employee of Abbott Nutrition. His role in the current study was assisting with the experimental design, helping with the interpretation of the results and the writing of the manuscript.

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Authors and Affiliations

  1. Department of Biology, Saint Mary’s College of California, 1928 Saint Mary’s Road, Moraga, CA, 94556, USA

    Jeffrey R. Bernard

  2. Exercise Physiology and Metabolism Laboratory, Department of Kinesiology and Health Education, University of Texas at Austin, Austin, TX, 78712, USA

    Yi-Hung Liao, Zhenping Ding, Daisuke Hara, Maximilian Kleinert & John L. Ivy

  3. Abbott Nutrition, Abbott Laboratories, Columbus, OH, 43215, USA

    Jeffrey L. Nelson

  4. Department of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei, 112, Taiwan

    Yi-Hung Liao

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  1. Jeffrey R. Bernard
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Correspondence to Jeffrey R. Bernard.

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Bernard, J.R., Liao, YH., Ding, Z. et al. An amino acid mixture improves glucose tolerance and lowers insulin resistance in the obese Zucker rat. Amino Acids 45, 191–203 (2013). https://doi.org/10.1007/s00726-013-1488-y

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  • DOI: https://doi.org/10.1007/s00726-013-1488-y

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