Research connects impaired glucose tolerance to a variety of adverse outcomes, including diabetes, heart disease, and neuropathy, but the cellular-level drivers for glucose tolerance levels are not comprehensively understood .1-4 An array of complex factors influence glucose tolerance, and metabolites’ relationship to that tolerance are now being studied as an important research area.5,6 For example, metabolomic analysis of glucose tolerance offers a comprehensive characterization of what occurs at a cellular level to drive glucose tolerance. These results can have implications for diabetes as well as other indications where glucose tolerance and resistance correlate with pathology.7 A recent Stanford University School of Medicine and Baylor College of Medicine study published in Nature details metabolites’ involvement in biochemical pathways and their impact on glucose tolerance.7
New Metabolites for Insulin Resistance Biomarkers
Researchers can leverage additional metabolite analysis to diagnose insulin resistance in patients. In particular, studies correlate fasting levels of specific metabolites linoleoylglycerophosphocholine (LGPC) and α-hydroxybutyrate (α-HB) with type 2 diabetes as well as dysglycemia.8 Such metabolic profiling offers an opportunity for determining impaired glucose tolerance via a fasting blood draw.8 Further, specific analytes present an opportunity to report on additional glucose-related organs, such as the liver, kidney, and muscles, where these metabolites are generated and consumed.
Aromatic Metabolite Lactoyl-Phenylalanine Improves Glucose Homeostasis
Certain aromatic metabolites correlate with impaired glucose tolerance and accumulate in the urine of obese patients, including N-lactoyl-phenylalanine (Lac-Phe). In particular, research identifies aromatic metabolites resulting from excessive intake of protein and fat.9 Further, data connect mitochondrial overload and impairment of insulin signaling to such aromatic metabolites.9
Lac-Phe, a blood-borne aromatic metabolite, is created by amino acids and lactate via protease cytosolic nonspecific dipeptidase reversed action.10 Increases in Lac-Phe production during exercise correlate with decreased eating and resulting in obesity.7 Lac-Phe is synthesized in CNDP2+ cells, such as monocytes, macrophages, as well as other epithelial and immune cells.7 Findings demonstrated improved glucose homeostasis due to increased exposure to Lac-Phe biosynthesis, indicating the propensity of Lac-Phe as a molecular effector.7 Further, studies connect Lac-Phe with insulin resistance, offering applications for predicting prediabetes as well as type 2 diabetes.11
Implications of Metabolites for Glucose Research
Given the different impacts of specific metabolites, research analysis could leverage these findings to drive new insights about the role of metabolites in glucose homeostasis for therapeutic indications. Metabolon offers several assays to support metabolomic analysis for research endeavors throughout the life sciences, including metabolomic analysis for diabetes. Contact the team at Metabolon to see how metabolomics and our platform can empower your research, too.
Ready to see what new insights metabolomics can help your research reveal? Contact us today to learn more.
- Kolter T, and Sandhoff K. “Sphingolipid metabolism diseases.” Biochimica et Biophysica Acta (BBA) – Biomembranes. 2006; 1758(12): 2057-2079. https://doi.org/10.1016/j.bbamem.2006.05.027.
- Hanada K. Sphingolipids in infectious diseases. Japanese journal of infectious diseases. 2005;58(3):131.
- Quinville BM, Deschenes NM, Ryckman AE, Walia JS. A Comprehensive Review: Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis. Int J Mol Sci. 2021;22(11):5793. doi: 10.3390/ijms22115793.
- Markwell MA, Svennerholm L, Paulson JC. “Specific gangliosides function as host cell receptors for Sendai virus.” Proc. Natl. Acad. Sci. U. S. A.. 1981; 78:5406-5410. https://doi.org/10.1073/pnas.78.9.5406
- Karlsson KA. Animal glycosphingolipids as membrane attachment sites for bacteria. Annual review of biochemistry. 1989; 58(1):309-50.
- Sandvig K, van Deurs B. “Transport of protein toxins into cells: pathways used by ricin, cholera toxin Shiga toxin.” FEBS Lett. 2022; 529: 49-53.
- De Wit NM, Den Hoedt S, Martinez-Martinez P, Rozemuller AJ, Mulder MT, De Vries HE. Astrocytic Ceramide as Possible Indicator of Neuroinflammation. J. Neuroinflamm. 2019;16:48. doi: 10.1186/s12974-019-1436-1.
- Yogi A, Callera GE, Aranha AB, Antunes TT, Graham D, Mcbride M, Dominiczak A, Touyz RM. Sphingosine-1-Phosphate-Induced Inflammation Involves Receptor Tyrosine Kinase Transactivation in Vascular Cells Upregulation in Hypertension. Hypertension. 2011. doi: 10.1161/HYPERTENSIONAHA.110.162719.
- Ammit AJ, Hastie AT, Edsall LC, Hoffman RK, Amrani Y, Krymskaya VP, Kane SA, Peters SP, Penn RB, Spiegel S, et al. Sphingosine 1-Phosphate Modulates Human Airway Smooth Muscle Cell Functions That Promote Inflammation and Airway Remodeling in Asthma. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2001;15:1212–1214. doi: 10.1096/fj.00-0742fje.
- Jolly PS, Rosenfeldt HM, Milstien S, Spiegel S. The Roles of Sphingosine-1-Phosphate in Asthma. Mol. Immunol. 2002;38:1239–1245. doi: 10.1016/S0161-5890(02)00070-6.
- Hong Choi O., Kim JH., Kinet JP. Calcium Mobilization via Sphingosine Kinase in Signalling by the FcɛRI Antigen Receptor. Nature. 1996;380:634–636. doi: 10.1038/380634a0.
- Prieschl EE, Csonga R, Novotny V, Kikuchi GE, Baumruker T. The Balance between Sphingosine and Sphingosine-1-Phosphate Is Decisive for Mast Cell Activation after Fc Epsilon Receptor I Triggering. J. Exp. Med. 1999;190:1–8. doi: 10.1084/jem.190.1.1.
- Mitselou A, Grammeniatis V, Varouktsi A, Papadatos SS, Katsanos K, Galani V. Proinflammatory Cytokines in Irritable Bowel Syndrome: A Comparison with Inflammatory Bowel Disease. Intest. Res. 2020;18:115–120. doi: 10.5217/ir.2019.00125.
- Ogretmen B. Sphingolipid Metabolism in Cancer Signalling and Therapy. Nat. Rev. Cancer. 2018;18:33–50. doi: 10.1038/nrc.2017.96.
- Holland WL, Knotts TA, Chavez JA, Wang LP, Hoehn KL, Summers SA. Lipid Mediators of Insulin Resistance. Nutr. Rev. 2007;65:S39–S46. doi: 10.1301/nr.2007.jun.S39-S46.