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Effect of calcium channel antagonists in modifying the inhibitory influence of adenosine on insulin secretion
N A Ismail1, A A Shaheen, M M el-Sawalhi
1Biochemistry Department, Faculty of Pharmacy, Cario University, Egypt.
Abstract:
The present work was performed to study the effect of two calcium channel antagonists, namely verapamil (CAS 52-53-9) and nifedipine (CAS 21829-25-4) in modifying the inhibitory influence of adenosine on insulin secretion from isolated rat pancreatic islets. The combined effect of adenosine and these agents on serum insulin and glucose levels in vivo was also investigated. Both verapamil and nifedipine at 100 mumol/l and 1 mumol/l, respectively, produced a significant inhibition of glucose-stimulated insulin secretion from pancreatic islets. Combination of these agents with adenosine 10 mumol/l did not modify the inhibitory effect of adenosine on insulin secretion. Verapamil (21.6 mg/kg b.wt.) and nifedipine (5.4 mg/kg b.wt.) intraperitoneally injected prior to glucose loading produced a significant increase in serum glucose with an accompanied decrease in serum insulin levels. Concurrent administration of verapamil with adenosine neither affected the hyperglycaemic nor the hypoinsulinaemic effects of adenosine, whereas combined administration of nifedipine and adenosine decreased the hyperglycaemic effect of adenosine but not its hypoinsulinaemic effect. These results may indicate that these calcium channel antagonists do not interact with adenosine receptors which mediate its inhibitory effect on insulin secretion.
Insights
Calcium channel blockers verapamil and nifedipine inhibit insulin secretion. Adenosine
Area of Science:
- Pharmacology
- Endocrinology
- Cell Biology
Background:
- Adenosine inhibits insulin secretion via specific receptors.
- Calcium channel blockers (CCBs) influence cellular processes.
Purpose of the Study:
- To investigate the interaction between CCBs (verapamil, nifedipine) and adenosine's effect on insulin secretion.
- To assess the in vivo effects of CCBs and adenosine on glucose and insulin levels.
Main Methods:
- Isolated rat pancreatic islets were used to study glucose-stimulated insulin secretion.
- In vivo experiments involved intraperitoneal injection of CCBs and glucose loading in rats.
- Serum insulin and glucose levels were measured.
Main Results:
- Both verapamil and nifedipine inhibited glucose-stimulated insulin secretion in vitro.
- Combined administration of CCBs with adenosine did not alter adenosine's inhibitory effect on insulin secretion.
- In vivo, verapamil and nifedipine increased serum glucose and decreased insulin levels.
- Nifedipine, but not verapamil, attenuated adenosine's hyperglycemic effect in vivo.
Conclusions:
- Calcium channel antagonists verapamil and nifedipine do not appear to interact with adenosine receptors mediating insulin secretion inhibition.
- The mechanisms underlying adenosine's effects on glucose and insulin metabolism may involve pathways distinct from direct CCB interaction.