Unlocking the Potential: Amino Acids’ Role in Predicting and Exploring Therapeutic Avenues for Type 2 Diabetes Mellitus
Abstract
:1. Introduction
2. The Interrelation between Amino Acids and T2DM
2.1. Branched-Chain Amino Acids
2.1.1. Branched-Chain Amino Acid Metabolism in Health and T2DM
2.1.2. Mechanisms Underlying Branched-Chain Amino Acids in T2DM
Role of mTORC1
BCAA Dysmetabolism
2.2. Aromatic Amino Acids
2.2.1. Phenylalanine and Tyrosine Metabolism
2.2.2. Tryptophan Metabolism
Tryptophan Metabolism in Health and T2DM
Mechanisms Underlying Tryptophan in T2DM
2.3. Glycine Metabolism
2.3.1. Glycine Metabolism in Health and T2DM
2.3.2. Mechanisms Underlying Glycine in T2DM
2.4. Asparagine and Aspartate
2.4.1. Asparagine Metabolism in Health and T2DM
2.4.2. Mechanisms Underlying Asparagine and Aspartate in T2DM
2.5. Serine Metabolism
2.5.1. Serine Metabolism in Health and T2DM
2.5.2. Mechanisms Underlying Serine in T2DM
2.6. Amino Acid Combination
3. Targeting Predictive Amino Acids for Preventive and Therapeutic Interventions in T2DM
3.1. Lifestyle Interventions
3.2. Pharmacologic Treatment Approaches
4. Conclusions and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Reference | Study Population Location | N, Follow-Up Time | Study Design | Biological Sample | Methods/Tested Amino Acids | Key Findings |
---|---|---|---|---|---|---|
Wang TJ et al., 2011 Nat Med [24] | Discovery analyses: Framingham Offspring Study, U.S. Replication analyses: Malmo Diet and Cancer Study, Sweden | Discovery analyses: 189 cases who developed diabetes during a 12-year follow-up period, and 189 propensity-matched controls who did not develop diabetes Replication analyses: 163 cases and 163 controls | Cohort Nested case-control study | Plasma | LC-MS isoleucine, leucine, valine, tyrosine, phenylalanine, tryptophan, arginine, lysine, histidine, aspartate, glutamic acid, asparagine, glutamine, methionine, serine, threonine, alanine, glycine, proline, cis/trans-hydroxyproline, taurine | Increased risk of T2DM (↑): isoleucine, leucine, valine, tyrosine, phenylalanine, sum of isoleucine, tyrosine and phenylalanine. Replication analyses: leucine, valine, tyrosine, and phenylalanine were significantly associated with increased risk of incident diabetes (↑). |
Ruiz-Canela M et al., 2018 Diabetologia [25] | PREvención con DIeta MEDiterránea (PREDIMED) trial | 251 T2DM, 694 controls (641 non-T2DM and 53 overlapping cases) 3.8 years | Cohort Nested case-control study | Plasma | LC-MS/MS leucine, isoleucine, valine, phenylalanine, tyrosine | Increased risk of T2DM (↑): baseline BCAA (sum of leucine, isoleucine and valine) and AAA (sum of phenylalanine and tyrosine) scores, BCAAs/AAAs, leucine, isoleucine, valine, phenylalanine, tyrosine. |
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Yamada, C. et al., 2015 J Diabetes Investig [40] | Volunteers Japan | 94 non-diabetic Japanese men and women | Cross-sectional study | Plasma | LC/MC serine, asparagine, glutamic acid, glutamine, and other 39 amino acids in total | (↑) Positive correlations were observed between HOMA-IR and valine, isoleucine, leucine, tyrosine, phenylalanine and total BCAA concentration. |
Floegel A et al., 2013 Diabetes [71] | European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam | 800 incident T2DM, 2282 controls 7 years | Cohortnested case-control study | Serum | Targeted FIA-MS/MS 163 metabolites (including 14 amino acids) | Decreased risk of T2DM (↓): glycine; increased risk of T2DM (↑): Phenylalanine. |
Vangipurapu, J. et al., 2020 Diabetes Care [75] | Metabolic Syndrome in Men (METSIM) study | 5169 participants of METSIM having a follow-up of 7.4 years | Population-based cohort | Plasma | UHPLC 86 microbiome-based metabolites | Increased risk of T2DM (↑): xanthurenate, kynurenate as tryptophan-kynurenine downstream metabolites |
Menni C et al., 2013 Diabetes [21] | Twins UK | 2204 female (115 T2DM, 192 IFG, 1897 control) | Population-based cohort | Plasma | Nontargeted metabolomicsprovider Metabolon, Inc.42 metabolites | Increased risk of T2DM (↑): proline, 3-Methyl-2-oxovalerate, 4-Methyl-2-oxopentanoate, isoleucine, leucine, valine; decreased risk of T2DM (↓): N-acetylglycine, citrulline, dimethylarginine (SDMA + ADMA); increased risk of IFG (↑): 2-hydroxybutyrate (AHB), 3-methyl-2-oxobutyrate, 3-Methyl-2-oxovalerate, 4-methyl-2-oxopentanoate, isoleucine, leucine. |
Tianlu Chen et al., 2016 Plos one [72] | Shanghai Diabetes Study (SHDS) | 213 NGT 10 years | Cohort population-based cohort | Serum | UPLC-TQ/MS tryptophan | (↑) Serum tryptophan was positively associated with T2DM risk. |
Rebholz, C.M. et al., 2018 Diabetologia [96] | Atherosclerosis Risk in Communities (ARIC) study | 2939 | Cohort population-based cohort | Serum | isoleucine, leucine, valine, asparagine, 3-(4-hydoxyphenyl) lactate | Increased risk of T2DM (↑): isoleucine, leucine, valine; decreased risk of T2DM (↓): asparagine |
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Ding, Y.; Wang, S.; Lu, J. Unlocking the Potential: Amino Acids’ Role in Predicting and Exploring Therapeutic Avenues for Type 2 Diabetes Mellitus. Metabolites 2023, 13, 1017. https://doi.org/10.3390/metabo13091017
Ding Y, Wang S, Lu J. Unlocking the Potential: Amino Acids’ Role in Predicting and Exploring Therapeutic Avenues for Type 2 Diabetes Mellitus. Metabolites. 2023; 13(9):1017. https://doi.org/10.3390/metabo13091017
Chicago/Turabian StyleDing, Yilan, Shuangyuan Wang, and Jieli Lu. 2023. "Unlocking the Potential: Amino Acids’ Role in Predicting and Exploring Therapeutic Avenues for Type 2 Diabetes Mellitus" Metabolites 13, no. 9: 1017. https://doi.org/10.3390/metabo13091017
APA StyleDing, Y., Wang, S., & Lu, J. (2023). Unlocking the Potential: Amino Acids’ Role in Predicting and Exploring Therapeutic Avenues for Type 2 Diabetes Mellitus. Metabolites, 13(9), 1017. https://doi.org/10.3390/metabo13091017