Alanine is a key gluconeogenic amino acid that can be converted to glucose in the liver. Alanine levels tend to increase when glucose and insulin are elevated.
Chen P-H, Chen J-D, Lin Y-C, Zhang Y, Xi L, Hong J, Chao M, Weiqiong G, Wang W, Ning G. Association of Alanine Aminotransferase Levels (ALT) with Insulin Resistance. World Journal of Gastroenterology (2012). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515498/
Tanaka S, et al.. Associations of alanine aminotransferase/aspartate aminotransferase with insulin resistance and β-cell function in women. Journal of Diabetes Investigation (2023). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185667/
Glutamic acid is another gluconeogenic amino acid that can supply carbon for glucose production. Glutamate may be increased when glucose is high and insulin resistance is present.
Hanako Nakajima, Hiroshi Okada, Ayaka Kobayashi, Fuyuko Takahashi, Takuro Okamura, Yoshitaka Hashimoto, Naoko Nakanishi, Takafumi Senmaru. Leucine and Glutamic Acid as a Biomarker of Sarcopenic Risk in Japanese People with Type 2 Diabetes. PLOS ONE (2023). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222500/
S. Sankar, R. Sivaraj, S. Sathishkumar, S. Suganya, K. Kavitha, S. Senthilkumar, S. Srinivasan, S. Sivakumar. Accelerated Healing of Diabetic Wounds Treated with L-Glutamic Acid-Loaded Chitosan Hydrogels. Scientific Reports (2017). https://www.nature.com/articles/s41598-017-10882-1
So Young Park, Jieun Kim, Jung Il Son, Sang Youl Rhee, Do-Yeon Kim, Suk Chon, Hyunjung Lim. Dietary glutamic acid and aspartic acid as biomarkers for predicting diabetic retinopathy. Nutrients (2021). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012375/
Isoleucine, the third branched-chain amino acid, also relates to glucose and insulin homeostasis. High isoleucine can suggest reduced insulin sensitivity.
Chan, S. S., Wong, G. W. K., & Yeo, G. S. H.. The Effect of Isoleucine Supplementation on Body Weight and Glucose Tolerance in Diet-Induced Obese Mice. Nutrients (2020). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468706/
Gao, P., & Newgard, C. B.. Comparative Effects of the Branched-Chain Amino Acids Leucine, Isoleucine, and Valine on Glucose Homeostasis in Humans. Nutrients (2021). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150294/
Lactic acid is produced from glucose through glycolysis and may accumulate when glucose is high, as in diabetes. Elevated lactic acid can indicate impaired glucose utilization.
D. Genuth, S. Lachin, J. Cleary, P. The Control Diabetes Study Group. The evaluation of intracellular energy metabolism in prediabetic patients: A comparison of the effects of intensive and conventional treatment strategies on leukocyte energy metabolism. Diabetologia (2021). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991880/
Jenny Lund, D. Margriet Ouwens, Marianne Wettergreen, Siril S. Bakke, G. Hege Thoresen. Increased Glycolysis and Higher Lactate Production in Hyperglycemic Myotubes. Frontiers in Physiology (2019). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770141/
E. Haythorne, M. Lloyd, J. Walsby-Tickle, et al.. Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells. Nature Communications (2022). https://www.nature.com/articles/s41467-022-34095-x
Like valine, leucine is a branched-chain amino acid that relates to glucose utilization and insulin signaling. Elevated leucine may indicate problems with glucose uptake and metabolism.
[A. A. Ahmed], [S. J. Lewis], [A. J. McKune], [L. J. van Lieshout], [J. J. W. Beelen]. “L-Leucine supplementation during energy restriction blunted the loss of FFM, enhanced the loss of fat mass (FM) and improved glucose tolerance”. Nature (2023). https://www.nature.com/articles/s41430-023-01360-1
Serine, which can be converted to glycine, is also a gluconeogenic amino acid that may be increased when glucose control is impaired.
Maddocks, O. D. K., et al.. Serine synthesis pathway inhibition cooperates with dietary serine and glycine restriction to limit cancer cell growth. Nature Communications (2021). https://www.nature.com/articles/s41467-020-20223-y
Valine is a branched-chain amino acid that can be oxidized for energy or converted to glucose. Higher levels can reflect impaired glucose metabolism and insulin resistance.
Hu, W., Yang, P., Fu, Z., Wang, Y., Zhou, Y., Ye, Z., … & Yang, T.. High L-Valine Concentrations Associate with Increased Oxidative Stress and Newly-Diagnosed Type 2 Diabetes Mellitus: A Cross-Sectional Study. Nutrients (2022). https://www.mdpi.com/2072-6643/14/4/827
Virtanen, J.K., Sivenius, J., Voutilainen, S., Tuomainen, T.P., & Salonen, J.T.. Nine Amino Acids Are Associated with Decreased Insulin Secretion and Increased Risk of Type 2 Diabetes: A 12-Year Follow-Up Study in the Finnish Population. Diabetes Care (2019). https://care.diabetesjournals.org/content/42/6/1103