Improved metabolic stimulus for glucose-induced insulin secretion through GK and PFK-2/FBPase-2 coexpression in insulin-producing RINm5F cells
| Autor: | Sara Langer, Sigurd Lenzen, Markus Tiedge, Simone Baltrusch, Laura Massa |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
endocrine system
medicine.medical_specialty Cell Survival Phosphofructokinase-2 medicine.medical_treatment Carbohydrate metabolism Transfection Cell Line Islets of Langerhans Endocrinology Adenosine Triphosphate Internal medicine Glucokinase Insulin Secretion Pyruvic Acid medicine Animals Humans Insulin Lactic Acid chemistry.chemical_classification biology Enzyme assay Rats Adenosine Diphosphate Enzyme Glucose Biochemistry chemistry Cell culture biology.protein Metabolic Networks and Pathways Phosphofructokinase Protein Binding |
| Zdroj: | Endocrinology. 147(12) |
| ISSN: | 0013-7227 |
| Popis: | The glucose sensor enzyme glucokinase plays a pivotal role in the regulation of glucose-induced insulin secretion in pancreatic β-cells. Activation of glucokinase represents a promising concept for the treatment of type 2 diabetes. Therefore, we analyzed the glucokinase activation through its physiological interaction partner, the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) and the resulting effect on glucose metabolism in insulin-producing cells. In RINm5F-GK-PFK-2/FBPase-2 cells stably overexpressing glucokinase plus islet PFK-2/FBPase-2, colocalization between both enzymes as well as elevation of glucokinase activity were significantly increased at a stimulatory glucose concentration of 10 mmol/liter. RINm5F-GK-PFK-2/FBPase-2 cells showed under this culture condition a significant increase in glucose utilization and in the ATP/ADP ratio compared with RINm5F-GK cells, which only overexpress glucokinase. Also glucose-induced insulin secretion was elevated in RINm5F-GK-PFK-2/FBPase-2 cells in comparison to RINm5F-GK cells. Furthermore, pyruvate accumulation and lactate production in RINm5F-GK-PFK-2/FBPase-2 cells were significantly lower at both 10 and 30 mmol/liter glucose than in RINm5F-GK and RINm5F cells. The significant improvement of glucose metabolism after PFK-2/FBPase-2 overexpression is apparently not exclusively the result of high glucokinase enzyme activity. Stabilization of the closed glucokinase conformation by PFK-2/FBPase-2 may not only activate the enzyme but also improve metabolic channeling in β-cells. |
| Databáze: | OpenAIRE |
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