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Exposure to glibenclamide increases rat beta cells sensitivity to glucose
1Institute of Internal Medicine, Endocrinology and Metabolism, 'Signorelli' Diabetes Center, University of Catania, Ospedale Garibaldi, Catania, Italy.
British Journal of Pharmacology
|March 1, 2000
Summary
Glibenclamide enhances beta-cell glucose sensitivity by increasing mitochondrial hexokinase activity, potentially explaining its hypoglycemic effects. This drug boosts glucose utilization and insulin secretion.
Area of Science:
- Biochemistry
- Endocrinology
- Pharmacology
Background:
- Pancreatic beta-cells regulate glucose homeostasis through insulin secretion.
- Sulfonylureas like glibenclamide are used to treat type 2 diabetes by stimulating insulin release.
Purpose of the Study:
- To investigate the mechanism by which glibenclamide enhances glucose sensitivity in pancreatic islets.
- To determine the role of hexokinase and glucokinase activity in glibenclamide-induced changes in glucose metabolism.
Main Methods:
- Islets were pre-exposed to glibenclamide or tolbutamide.
- Glucose-stimulated insulin secretion and glucose utilization were measured.
- Hexokinase (HK) and glucokinase (GK) activities were assessed in cytosolic and mitochondrial fractions.
- Hexokinase binding to mitochondria was inhibited using dicyclohexylcarbodiimide (DCC).
Main Results:
- Glibenclamide, but not tolbutamide, increased glucose sensitivity and utilization in islets.
- Mitochondrial hexokinase activity significantly increased after glibenclamide exposure, without altering enzyme protein content.
- Glucokinase activity remained unchanged.
- Inhibition of hexokinase binding to mitochondria abolished the glibenclamide-induced increase in glucose sensitivity.
Conclusions:
- Short-term glibenclamide exposure increases beta-cell sensitivity to glucose.
- This effect is associated with enhanced mitochondrial hexokinase activity.
- Increased mitochondrial hexokinase may contribute to the hypoglycemic action of glibenclamide.