Insulin
Insulin is a hormone that regulates blood sugar levels by allowing glucose to enter cells for energy. High levels of insulin can indicate insulin resistance or prediabetes.
iollo markers that associate with Insulin
Alanine
Alanine is released by skeletal muscle during fasting and is a substrate for hepatic gluconeogenesis, so it may influence insulin sensitivity.
References
References
J. Virtanen, M. Laine, T. Tuomainen, et al.. Nine Amino Acids Are Associated With Decreased Insulin Secretion and Increased Fasting and 2-h Glucose Levels. Diabetes Care (2019). https://diabetesjournals.org/diabetes/article/68/6/1353/39714/Nine-Amino-Acids-Are-Associated-With-Decreased
A. R. Tricarico, A. A. Richards, et al.. Effect of Carnosine or β-Alanine Supplementation on Markers of Glycemic Control in Humans and Rodents. Nutrients (2022). https://www.mdpi.com/2072-6643/14/1/120
J. R. Stanley, K. R. McClenaghan, et al.. Metabolism of l-Alanine Is Important to the Regulation of Insulin Secretion. Diabetes (2010). https://diabetesjournals.org/diabetes/article/51/6/1714/14215/A-Nuclear-Magnetic-Resonance-Based-Demonstration
Y. Zhang, Y. Wang, et al.. Insulin Stimulates β-Alanine Uptake in Skeletal Muscle Cells in Vitro. PLOS ONE (2021). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0259860
S. Minato-Inokawa, A. Tsuboi-Kaji, et al.. Associations of Alanine Aminotransferase/Aspartate Aminotransferase with Insulin Resistance and β-Cell Function in Women. Nutrients (2023). https://www.mdpi.com/2072-6643/15/5/1158
Ceramides
Ceramides are lipid molecules that can accumulate in tissues and interfere with insulin signaling. Elevated ceramide levels are associated with insulin resistance and an increased risk of metabolic disorders like type 2 diabetes.
References
References
Lemaitre, R.N., Yu, C., Hoofnagle, A., Hari, N., Jensen, P.N., Fretts, A.M., Umans, J.G., Howard, B.V., Sitlani, C.M., Siscovick, D.S., King, I.B., Sotoodehnia, N., McKnight, B.. Circulating sphingolipids, insulin, HOMA-IR and HOMA-B: the Strong Heart Family Study.. Diabetes (2018). https://pubmed.ncbi.nlm.nih.gov/29588286/
Holland, W.L., Summers, S.A.. Strong Heart, Low Ceramides. Diabetes (2018). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054437/
Walker, M.E., Xanthakis, V., Peterson, L.R., Duncan, M.S., Lee, J., Ma, J., Bigornia, S., Moore, L.L., Quatromoni, P.A., Vasan, R.S., Jacques, P.F.. Dietary Patterns, Ceramide Ratios, and Risk of All-Cause and Cause-Specific Mortality: The Framingham Offspring Study. The Journal of Nutrition (2020). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675031/
Neeland, I.J., Singh, S., McGuire, D.K., Vega, G.L., Roddy, T., Reilly, D.F., Castro-Perez, J., Kozlitina, J., Scherer, P.E.. Relation of plasma ceramides to visceral adiposity, insulin resistance and the development of type 2 diabetes mellitus: the Dallas Heart Study. Diabetologia (2018). https://pubmed.ncbi.nlm.nih.gov/30159588/
Hla, T., Kolesnick, R.. C16:0-Ceramide Signals Insulin Resistance. Cell Metabolism (2014). https://www.cell.com/action/showPdf?pii=S1550-4131%2814%2900464-1
Glutamic Acid
Glutamate is a precursor to the neurotransmitter GABA which regulates pancreatic insulin secretion. Elevated glutamate may impair insulin response.
References
References
A. B. Walls, H. S. Waagepetersen, L. K. Bak, A. Schousboe, U. Sonnewald. The role of GABA in islet function. Scientific Reports (2021). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9558271/
A. Martin, G. J. Mick, H. M. Choat, et al.. A randomized trial of oral gamma aminobutyric acid (GABA) or the combination of GABA with glutamic acid decarboxylase (GAD) on pancreatic islet endocrine function in children with newly diagnosed type 1 diabetes. Nature Communications (2022). https://doi.org/10.1038/s41467-022-35544-3
Isoleucine
Isoleucine, along with other branched-chain amino acids, is linked to insulin resistance and metabolic syndrome, possibly by activating mTOR signaling.
References
References
R. F. Sirap-U, L. C. Ed. Lacsap-Na. Branched-Chain Amino Acids and Insulin Resistance, from Protein Supply to Diet-Induced Obesity. Frontiers in Nutrition (2022). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9824001/
Xue Zhao, Qing Han, Yujia Liu, Chenglin Sun, Xiaokun Gang, Guixia Wang. The Relationship between Branched-Chain Amino Acid Related Metabolomic Signature and Insulin Resistance: A Systematic Review. Nutrients (2022). https://www.mdpi.com/2072-6643/14/16/3446
A. J. M. Willems, M. J. van Baak, E. J. M. Fliers, C. P. van der Vusse, H. C. M. Sips. Intragastric administration of leucine or isoleucine lowers the blood glucose in response to a mixed-nutrient drink in healthy subjects. Metabolism: Clinical and Experimental (2022). https://www.sciencedirect.com/science/article/pii/S0002916522046597
K. Shimada, T. Kita, S. Yoshino, H. Matsumoto, S. Sugiura, S. Kajimoto, Y. Sato, H. Kume, T. Sugiura. Isoleucine, a Blood Glucose-Lowering Amino Acid. Journal of Biochemistry (2022). https://onlinelibrary.wiley.com/doi/abs/10.1093/jb/mvac038
Leucine
Leucine, a branched-chain amino acid, is associated with insulin resistance and impaired insulin signaling, increasing risk of metabolic disorders.
References
References
E. Binder, F.J. Bermúdez-Silva, C. André, M. Elie, S.Y. Romero-Zerbo, T. Leste-Lasserre, et al.. Leucine Supplementation Protects from Insulin Resistance by Regulating Adiposity Levels. PLoS ONE (2013). https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0074705
A.L. Newgard, J.B. An, J.R. Baur, R.S. Kennedy, J.M. Liu, J.R. Malaisse, et al.. The possible role of leucine in modulating glucose homeostasis. Trends in Endocrinology and Metabolism (2012). https://www.sciencedirect.com/science/article/pii/S0306987712004410
J. Yang, Y. Chi, B.R. Burkhardt, Y. Guan, B.A. Wolf. Leucine metabolism in regulation of insulin secretion from pancreatic beta cells. Peking University Medical Press (2010). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2969169/
J. Zhang, W. Xu, H. Han, L. Zhang, T. Wang. Dietary Leucine Supplementation Restores Serum Glucose Levels, and Modifying Hepatic Gene Expression Related to the Insulin Signal Pathway in IUGR Piglets. Animals (2019). https://www.mdpi.com/2076-2615/9/12/1138
Phenylalanine
Aromatic amino acids like phenylalanine tend to be elevated in insulin resistant states and are predictive of future diabetes risk.
References
References
J. Virtanen, T. M. Sjöholm, J. Tuomainen, M. Voutilainen, A. H. Hakkarainen, J. T. Salonen, M. Laine, U. S. Kähönen. Nine Amino Acids Are Associated With Decreased Insulin Secretion and Elevated Glucose Levels in a Middle-Aged and Elderly Finnish Population. Diabetes (2019). https://diabetesjournals.org/diabetes/article/68/6/1353/39714/Nine-Amino-Acids-Are-Associated-With-Decreased
X. Wang, J. Li, Y. Xu, Y. Wang, Y. Li, J. Li, L. Zhang, Y. Zhang, J. Chen, Y. Wang, et al.. Phenylalanine impairs insulin signaling and inhibits glucose uptake through modification of IRβ. Science Advances (2022). https://pubmed.ncbi.nlm.nih.gov/35879296/
Y. Zhang, X. Wang, J. Li, Y. Xu, Y. Li, J. Li, L. Zhang, Y. Zhang, J. Chen, Y. Wang, et al.. Phenylalanine impairs insulin signaling and inhibits glucose uptake in cultured cells. Biomedicines (2022). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314339/
J. Mohás-Cseh, G. A. Molnár, M. Pap, B. Laczy, T. Vas, M. Kertész, K. Németh, C. Hetényi, O. Csikós, G. K. Tóth, et al.. Incorporation of Oxidized Phenylalanine Derivatives into Insulin Signaling Relevant Proteins May Link Oxidative Stress to Biomedicines. Biomedicines (2022). https://www.mdpi.com/2227-9059/10/5/975
Tyrosine
Tyrosine, an aromatic amino acid, is associated with insulin resistance and risk of developing type 2 diabetes in epidemiological studies.
References
References
Guan, W., Wang, Y., Zhu, J., Li, J., Zhang, J., Zhang, H., … & Zhang, P.. Plasma tyrosine and its interaction with low high‐density lipoprotein cholesterol in the risk of type 2 diabetes mellitus in Chinese patients. Journal of Diabetes Investigation (2019). https://onlinelibrary.wiley.com/doi/abs/10.1111/jdi.12966
Kawanaka, M., Nishino, K., Oka, T., Urata, N., Nakamura, J., Suehiro, M., … & Yamada, G.. Tyrosine levels are associated with insulin resistance in patients with nonalcoholic fatty liver disease. Hormone and Metabolic Research (2015). https://www.dovepress.com/tyrosine-levels-are-associated-with-insulin-resistance-in-patients-wit-peer-reviewed-fulltext-article-HMER
Valine
Branched-chain amino acids like valine are associated with insulin resistance and risk of type 2 diabetes, likely by disrupting insulin signaling pathways.
References
References
Zhang, Y., Chen, J., Li, X., & Zhang, Y.. Valine Supplementation Does Not Reduce Lipid Accumulation and Insulin Resistance in High-Fat Diet-Induced Obese Mice. ACS Omega (2020). https://pubs.acs.org/doi/10.1021/acsomega.0c03707
Xie, X., Li, Q., Li, S., & Wang, J.. The Relationship between Branched-Chain Amino Acids and Insulin Resistance in Humans: A Systematic Review and Meta-Analysis. Frontiers in Nutrition (2023). https://www.frontiersin.org/articles/10.3389/fnut.2023.1189982/full
Insulin
Insulin is a hormone that regulates blood sugar levels by allowing glucose to enter cells for energy. High levels of insulin can indicate insulin resistance or prediabetes.
iollo markers that associate with Insulin
Alanine
Alanine is released by skeletal muscle during fasting and is a substrate for hepatic gluconeogenesis, so it may influence insulin sensitivity.
References
References
J. Virtanen, M. Laine, T. Tuomainen, et al.. Nine Amino Acids Are Associated With Decreased Insulin Secretion and Increased Fasting and 2-h Glucose Levels. Diabetes Care (2019). https://diabetesjournals.org/diabetes/article/68/6/1353/39714/Nine-Amino-Acids-Are-Associated-With-Decreased
A. R. Tricarico, A. A. Richards, et al.. Effect of Carnosine or β-Alanine Supplementation on Markers of Glycemic Control in Humans and Rodents. Nutrients (2022). https://www.mdpi.com/2072-6643/14/1/120
J. R. Stanley, K. R. McClenaghan, et al.. Metabolism of l-Alanine Is Important to the Regulation of Insulin Secretion. Diabetes (2010). https://diabetesjournals.org/diabetes/article/51/6/1714/14215/A-Nuclear-Magnetic-Resonance-Based-Demonstration
Y. Zhang, Y. Wang, et al.. Insulin Stimulates β-Alanine Uptake in Skeletal Muscle Cells in Vitro. PLOS ONE (2021). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0259860
S. Minato-Inokawa, A. Tsuboi-Kaji, et al.. Associations of Alanine Aminotransferase/Aspartate Aminotransferase with Insulin Resistance and β-Cell Function in Women. Nutrients (2023). https://www.mdpi.com/2072-6643/15/5/1158
Ceramides
Ceramides are lipid molecules that can accumulate in tissues and interfere with insulin signaling. Elevated ceramide levels are associated with insulin resistance and an increased risk of metabolic disorders like type 2 diabetes.
References
References
Lemaitre, R.N., Yu, C., Hoofnagle, A., Hari, N., Jensen, P.N., Fretts, A.M., Umans, J.G., Howard, B.V., Sitlani, C.M., Siscovick, D.S., King, I.B., Sotoodehnia, N., McKnight, B.. Circulating sphingolipids, insulin, HOMA-IR and HOMA-B: the Strong Heart Family Study.. Diabetes (2018). https://pubmed.ncbi.nlm.nih.gov/29588286/
Holland, W.L., Summers, S.A.. Strong Heart, Low Ceramides. Diabetes (2018). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054437/
Walker, M.E., Xanthakis, V., Peterson, L.R., Duncan, M.S., Lee, J., Ma, J., Bigornia, S., Moore, L.L., Quatromoni, P.A., Vasan, R.S., Jacques, P.F.. Dietary Patterns, Ceramide Ratios, and Risk of All-Cause and Cause-Specific Mortality: The Framingham Offspring Study. The Journal of Nutrition (2020). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675031/
Neeland, I.J., Singh, S., McGuire, D.K., Vega, G.L., Roddy, T., Reilly, D.F., Castro-Perez, J., Kozlitina, J., Scherer, P.E.. Relation of plasma ceramides to visceral adiposity, insulin resistance and the development of type 2 diabetes mellitus: the Dallas Heart Study. Diabetologia (2018). https://pubmed.ncbi.nlm.nih.gov/30159588/
Hla, T., Kolesnick, R.. C16:0-Ceramide Signals Insulin Resistance. Cell Metabolism (2014). https://www.cell.com/action/showPdf?pii=S1550-4131%2814%2900464-1
Glutamic Acid
Glutamate is a precursor to the neurotransmitter GABA which regulates pancreatic insulin secretion. Elevated glutamate may impair insulin response.
References
References
A. B. Walls, H. S. Waagepetersen, L. K. Bak, A. Schousboe, U. Sonnewald. The role of GABA in islet function. Scientific Reports (2021). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9558271/
A. Martin, G. J. Mick, H. M. Choat, et al.. A randomized trial of oral gamma aminobutyric acid (GABA) or the combination of GABA with glutamic acid decarboxylase (GAD) on pancreatic islet endocrine function in children with newly diagnosed type 1 diabetes. Nature Communications (2022). https://doi.org/10.1038/s41467-022-35544-3
Isoleucine
Isoleucine, along with other branched-chain amino acids, is linked to insulin resistance and metabolic syndrome, possibly by activating mTOR signaling.
References
References
R. F. Sirap-U, L. C. Ed. Lacsap-Na. Branched-Chain Amino Acids and Insulin Resistance, from Protein Supply to Diet-Induced Obesity. Frontiers in Nutrition (2022). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9824001/
Xue Zhao, Qing Han, Yujia Liu, Chenglin Sun, Xiaokun Gang, Guixia Wang. The Relationship between Branched-Chain Amino Acid Related Metabolomic Signature and Insulin Resistance: A Systematic Review. Nutrients (2022). https://www.mdpi.com/2072-6643/14/16/3446
A. J. M. Willems, M. J. van Baak, E. J. M. Fliers, C. P. van der Vusse, H. C. M. Sips. Intragastric administration of leucine or isoleucine lowers the blood glucose in response to a mixed-nutrient drink in healthy subjects. Metabolism: Clinical and Experimental (2022). https://www.sciencedirect.com/science/article/pii/S0002916522046597
K. Shimada, T. Kita, S. Yoshino, H. Matsumoto, S. Sugiura, S. Kajimoto, Y. Sato, H. Kume, T. Sugiura. Isoleucine, a Blood Glucose-Lowering Amino Acid. Journal of Biochemistry (2022). https://onlinelibrary.wiley.com/doi/abs/10.1093/jb/mvac038
Leucine
Leucine, a branched-chain amino acid, is associated with insulin resistance and impaired insulin signaling, increasing risk of metabolic disorders.
References
References
E. Binder, F.J. Bermúdez-Silva, C. André, M. Elie, S.Y. Romero-Zerbo, T. Leste-Lasserre, et al.. Leucine Supplementation Protects from Insulin Resistance by Regulating Adiposity Levels. PLoS ONE (2013). https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0074705
A.L. Newgard, J.B. An, J.R. Baur, R.S. Kennedy, J.M. Liu, J.R. Malaisse, et al.. The possible role of leucine in modulating glucose homeostasis. Trends in Endocrinology and Metabolism (2012). https://www.sciencedirect.com/science/article/pii/S0306987712004410
J. Yang, Y. Chi, B.R. Burkhardt, Y. Guan, B.A. Wolf. Leucine metabolism in regulation of insulin secretion from pancreatic beta cells. Peking University Medical Press (2010). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2969169/
J. Zhang, W. Xu, H. Han, L. Zhang, T. Wang. Dietary Leucine Supplementation Restores Serum Glucose Levels, and Modifying Hepatic Gene Expression Related to the Insulin Signal Pathway in IUGR Piglets. Animals (2019). https://www.mdpi.com/2076-2615/9/12/1138
Phenylalanine
Aromatic amino acids like phenylalanine tend to be elevated in insulin resistant states and are predictive of future diabetes risk.
References
References
J. Virtanen, T. M. Sjöholm, J. Tuomainen, M. Voutilainen, A. H. Hakkarainen, J. T. Salonen, M. Laine, U. S. Kähönen. Nine Amino Acids Are Associated With Decreased Insulin Secretion and Elevated Glucose Levels in a Middle-Aged and Elderly Finnish Population. Diabetes (2019). https://diabetesjournals.org/diabetes/article/68/6/1353/39714/Nine-Amino-Acids-Are-Associated-With-Decreased
X. Wang, J. Li, Y. Xu, Y. Wang, Y. Li, J. Li, L. Zhang, Y. Zhang, J. Chen, Y. Wang, et al.. Phenylalanine impairs insulin signaling and inhibits glucose uptake through modification of IRβ. Science Advances (2022). https://pubmed.ncbi.nlm.nih.gov/35879296/
Y. Zhang, X. Wang, J. Li, Y. Xu, Y. Li, J. Li, L. Zhang, Y. Zhang, J. Chen, Y. Wang, et al.. Phenylalanine impairs insulin signaling and inhibits glucose uptake in cultured cells. Biomedicines (2022). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314339/
J. Mohás-Cseh, G. A. Molnár, M. Pap, B. Laczy, T. Vas, M. Kertész, K. Németh, C. Hetényi, O. Csikós, G. K. Tóth, et al.. Incorporation of Oxidized Phenylalanine Derivatives into Insulin Signaling Relevant Proteins May Link Oxidative Stress to Biomedicines. Biomedicines (2022). https://www.mdpi.com/2227-9059/10/5/975
Tyrosine
Tyrosine, an aromatic amino acid, is associated with insulin resistance and risk of developing type 2 diabetes in epidemiological studies.
References
References
Guan, W., Wang, Y., Zhu, J., Li, J., Zhang, J., Zhang, H., … & Zhang, P.. Plasma tyrosine and its interaction with low high‐density lipoprotein cholesterol in the risk of type 2 diabetes mellitus in Chinese patients. Journal of Diabetes Investigation (2019). https://onlinelibrary.wiley.com/doi/abs/10.1111/jdi.12966
Kawanaka, M., Nishino, K., Oka, T., Urata, N., Nakamura, J., Suehiro, M., … & Yamada, G.. Tyrosine levels are associated with insulin resistance in patients with nonalcoholic fatty liver disease. Hormone and Metabolic Research (2015). https://www.dovepress.com/tyrosine-levels-are-associated-with-insulin-resistance-in-patients-wit-peer-reviewed-fulltext-article-HMER
Valine
Branched-chain amino acids like valine are associated with insulin resistance and risk of type 2 diabetes, likely by disrupting insulin signaling pathways.
References
References
Zhang, Y., Chen, J., Li, X., & Zhang, Y.. Valine Supplementation Does Not Reduce Lipid Accumulation and Insulin Resistance in High-Fat Diet-Induced Obese Mice. ACS Omega (2020). https://pubs.acs.org/doi/10.1021/acsomega.0c03707
Xie, X., Li, Q., Li, S., & Wang, J.. The Relationship between Branched-Chain Amino Acids and Insulin Resistance in Humans: A Systematic Review and Meta-Analysis. Frontiers in Nutrition (2023). https://www.frontiersin.org/articles/10.3389/fnut.2023.1189982/full