12/17/2025
An extra-credit post from biochemistry student Malinda Batassa!
Diabetes mellitus (DM) is a chronic disease, with Type 2 (T2DM) comprising over 90% of all cases and affecting almost 10% of the world’s population. This complex disease is commonly identified by elevated blood glucose levels resulting from one or both of improper insulin secretion by the pancreas, and a lack of sensitivity to insulin-response. Have you ever wondered what actually causes the elevated blood glucose levels in someone with DM? In this fall semester of CHEM 324, Chemistry of Biological Systems, we learned about glycolysis, a metabolic pathway our bodies rely on to regulate glucose levels in our bloodstream and produce energy.
Pancreatic β-cells are the primary source of insulin production. Typically, glucose is taken into the pancreas via glucose transporter 2 (GLUT2). Once glucose enters the pancreas, GLUT2 interacts with glucokinase and signals to insulin receptors secrete the insulin. Oftentimes those with T2DM have a defect in GLUT2, which interrupts the sensing of glucose, and fails to secrete insulin from the pancreas to enter the muscles and fat cells. Glucose transporter 4 (GLUT4) is another transporter protein, except it is found in muscle and fat cells. When insulin is secreted from the pancreatic β-cells, insulin signals to GLUT4 to move from inside the cell to the cell membrane, which allows glucose to enter the cell. However, in people with T2DM, failure of GLUT4 to move to the cell membrane from a lack or delayed response to insulin signaling then prevents glucose from entering muscle and fat cells. This leaves glucose in the bloodstream instead. As a result of both these impairments, glucose levels within the bloodstream remain elevated, which is characteristic of T2DM.
In relation to glycolysis, DM inhibits glucose breakdown, which causes a decrease in glycolytic flux. More importantly, less ATP is generated, meaning less energy is available for use. So while still complex, the cause of this disease can be simplified: when someone with T2DM who consumes a large candy bar or a carb-rich meal, their high blood sugar is a result of improper insulin production in the pancreas, and a lack of insulin response in the fat or muscle cells leaving glucose in the bloodstream instead of converting it into usable energy.
References
Wang, T.; Wang, J.; Hu, X.; Huang, X.-J.; Chen, G.-X. Current Understanding of Glucose Transporter 4 Expression and Functional Mechanisms. World J Biol Chem 2020, 11 (3), 76–98. https://doi.org/10.4331/wjbc.v11.i3.76.
Banday, M. Z.; Sameer, A. S.; Nissar, S. Pathophysiology of Diabetes: An Overview. Avicenna J Med 2020, 10 (4), 174–188. https://doi.org/10.4103/ajm.ajm_53_20.
Galicia-Garcia, U.; Benito-Vicente, A.; Jebari, S.; Larrea-Sebal, A.; Siddiqi, H.; Uribe, K. B.; Ostolaza, H.; Martín, C. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci 2020, 21 (17), 6275. https://doi.org/10.3390/ijms21176275.
Liu, Q.-J.; Yuan, W.; Yang, P.; Shao, C. Role of Glycolysis in Diabetic Atherosclerosis. World J Diabetes 2023, 14 (10), 1478–1492. https://doi.org/10.4239/wjd.v14.i10.1478.
Figure Credit:
Aguillard, A. GLP-1 Receptor Agonists as Treatments for Type 2 Diabetes. The Pipeline Blog, March 2023. https://medrac.web.unc.edu/2025/03/glp-1-receptor-agonists/