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- Title
Glycosylated Sulfonylurea (2DGs) Activates AMPK/p38 MAPK/ GLUT 4 Pathway In L6 Skeletal Muscle Cell Line.
- Authors
Nalweyiso, Jacinta; Hui, Tan Yong; Ghadeer, Suaifan; Anisa Fromming, Gabriele Ruth; Johnson, Stanlas; Morak-Mlodawska, Beata; Okechukwu, Patrick Nwabueze
- Abstract
Introduction: Sulfonylureas have been used widely for close to 50 years in the battle against type 2 diabetes mellitus. Their ability to elevate insulin secretion by the pancreatic β cells reduces hyperglycemia and glycated haemoglobin (HbA1c) levels in these patients. However, side effects like hypoglycemia, cardiovascular mortality risks and weight gain have increased their caution for use, hence the need for continuous research to minimize or eradicate these side effects while maintaining or improving their activity and efficacy. Novel glycosylated sulfonylurea (2DGs) was developed by integrating an aryl sulfonamide with a glucosamine moiety. Previous research has shown that it has superior in vitro and in vivo antidiabetic activity to the current third-generation sulfonylurea, glimepiride. It also exhibits anti- AGE and antioxidant properties coupled with lipid metabolism regulation and reduction in cardiovascular and renal side effects. 2DGs activates insulin signalling via the insulin-dependent IRS/PI3K/PKC/AKT pathway. The current study seeks to evaluate glucose uptake via the insulin-independent pathway AMPK/p38Mapk/GLUT4 pathway. Methods: The rate of glucose uptake in normal differentiated ATCC grade L6 skeletal muscle cells were evaluated using the Promega 2NBDG Glucose Uptake Assay kit. Treatment was done with or without insulin, tolbutamide and 2DGS at different concentrations. The synergetic effect of insulin and 2DGs was also studied. Western blot and ELISA were done on the cell lysates to evaluate AMPK and p38Mapk phosphorylation. Results: A higher significant dose-dependent increase in glucose uptake and GLUT 4, AMPK and p38 Mapk expression and phosphorylation was observed in 2DGs compared to the tolbutamide treated and negative groups. A significantly higher synergetic effect in cells treated with insulin and 2DGs was also observed. Conclusion: 2DGs treatment increases glucose uptake via the activation of the AMPK/p38Mapk/GLUT 4 pathway in normal differentiated L6 Skeletal Muscle cells.
- Subjects
SKELETAL muscle; MUSCLE cells; SULFONYLUREAS; TYPE 2 diabetes; CELL lines
- Publication
Malaysian Journal of Medicine & Health Sciences, 2022, Vol 18, p68
- ISSN
1675-8544
- Publication type
Abstract