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Updated: Aug 11, 2026
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High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
Published on: January 23, 2018
Time-dependent effects of cholinergic stimulation on beta cell responsiveness
W S Zawalich1, K C Zawalich, G G Kelley
1Yale University School of Nursing, 25 Park Street, PO Box 9740, New Haven, CT 06536-0740, USA.
Pflugers Archiv : European Journal of Physiology
|August 1, 1996
Summary
Cholinergic stimulation acutely enhances insulin secretion and phosphoinositide (PI) hydrolysis in rat islets. However, prolonged exposure desensitizes beta cells, impairing responses, suggesting phospholipase C activation is key to insulin release.
Area of Science:
- Endocrinology
- Cell Biology
- Metabolism
Background:
- Cholinergic stimulation influences pancreatic beta cell function.
- Phosphoinositide (PI) hydrolysis is implicated in cellular signaling pathways.
- Understanding these mechanisms is crucial for metabolic research.
Purpose of the Study:
- To investigate the acute and chronic effects of cholinergic stimulation on insulin secretion and PI responses in rat islets.
- To elucidate the role of PI hydrolysis in mediating beta cell responses to cholinergic agonists.
- To determine the impact of prolonged cholinergic exposure on glucose- and agonist-stimulated insulin release.
Main Methods:
- Isolated rat islets were used to measure insulin secretion and PI hydrolysis.
- Acute and chronic exposure protocols to carbachol (a cholinergic agonist) were employed.
- Radioactive [3H]inositol labeling was used to track PI metabolism.
- Atropine was used to block muscarinic receptor effects.
Main Results:
- Acute carbachol (10 microM) significantly potentiated glucose-stimulated insulin secretion and increased inositol phosphate accumulation.
- Chronic carbachol exposure (3.5 h) desensitized beta cells, abolishing responses to glucose and carbachol, though tolbutamide remained effective.
- Prolonged carbachol exposure impaired PI hydrolysis and glucose-stimulated insulin release, effects partially reversed by atropine.
Conclusions:
- Changes in PI hydrolysis closely parallel insulin secretory responses to cholinergic stimulation.
- Alterations in phospholipase C activation likely contribute significantly to observed insulin secretory patterns.
- Beta cell responses to cholinergic agonists involve complex desensitization mechanisms upon prolonged exposure.
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