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Published on: January 23, 2018
Resveratrol inhibits insulin secretion from rat pancreatic islets
1Department of Animal Physiology and Biochemistry, August Cieszkowski University of Agriculture, 60-637 Wolynska 35, Poznan, Poland. tszkudel@jay.au.poznan.pl
Abstract:
Resveratrol is a naturally occurring phytoalexin exerting cardioprotective, anticancer and antioxidant action. The most recent investigations have demonstrated that this compound plays a beneficial role alleviating some diabetic complications. However, resveratrols' influence on the endocrine function of the pancreas is unknown. The objective of the present study was to determine whether resveratrol affects insulin secretion from freshly isolated rat pancreatic islets. Incubations of pancreatic islets with resveratrol (1-100 microM, 90 min) revealed that the release of insulin induced by 6.6 and 16.6 mM glucose was substantially restricted by this compound in a concentration-dependent manner. This effect was not permanent and disappeared after resveratrol withdrawal from the buffer. However, the proper hormone secretion was not restored when glucose was replaced by other secretagogues - leucine with glutamine - indicating that disturbances other than the inhibition of glucose transport and glycolysis were responsible for the resveratrol-evoked reduction in insulin secretion. Glucose-induced insulin release tested in the presence of the sulfonylurea glibenclamide was also found to be reduced by resveratrol. Moreover, the activation of adenylyl cyclase by forskolin did not restrict the inhibitory effect of resveratrol on glucose-induced insulin release. In contrast, phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, suppressed completely the inhibitory effect of 1 and 10 microM resveratrol on insulin release. However, this compound at the highest concentration tested diminished its secretion even in the presence of PMA. The perifusion studies revealed that the depression of insulin release caused by resveratrol began a few minutes after its addition to the medium. Results obtained in the present investigations demonstrate that resveratrol is a compound exerting a clear-cut, but reversible inhibitory effect on insulin secretion from isolated pancreatic islets.
Insights
Resveratrol inhibits insulin secretion from pancreatic islets in a reversible manner. This compound affects glucose-induced insulin release, with effects modulated by protein kinase C activation.
Area of Science:
- Endocrinology
- Molecular Biology
- Pharmacology
Background:
- Resveratrol, a natural phytoalexin, exhibits cardioprotective, anticancer, and antioxidant properties.
- Recent studies suggest resveratrol may alleviate diabetic complications.
- The impact of resveratrol on pancreatic islet endocrine function remains largely unexplored.
Purpose of the Study:
- To investigate the effect of resveratrol on insulin secretion from isolated rat pancreatic islets.
- To determine the concentration-dependent effects of resveratrol on glucose-stimulated insulin release.
- To elucidate the mechanisms underlying resveratrol's influence on insulin secretion.
Main Methods:
- Incubation of freshly isolated rat pancreatic islets with varying concentrations of resveratrol.
- Stimulation of insulin release using glucose, leucine with glutamine, and forskolin.
- Assessment of insulin secretion in the presence of glibenclamide and phorbol 12-myristate 13-acetate (PMA).
- Perifusion studies to analyze the time course of resveratrol's effect.
Main Results:
- Resveratrol significantly inhibited glucose-induced insulin release in a concentration-dependent manner.
- The inhibitory effect was reversible upon removal of resveratrol.
- Resveratrol's inhibition was not restored by other secretagogues, suggesting mechanisms beyond glucose transport or glycolysis.
- Resveratrol reduced glucose-induced insulin release even in the presence of glibenclamide and forskolin.
- Phorbol 12-myristate 13-acetate (PMA) abolished the inhibitory effect of low resveratrol concentrations but not the highest tested concentration.
Conclusions:
- Resveratrol exerts a clear, reversible inhibitory effect on insulin secretion from pancreatic islets.
- The mechanism of inhibition involves pathways sensitive to protein kinase C activation.
- These findings highlight a potential concern regarding resveratrol supplementation in diabetic individuals, impacting pancreatic islet function.
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