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Am J Physiol Endocrinol Metab. 2019 Apr 23. doi: 10.1152/ajpendo.00385.2018. [Epub ahead of print]

The autonomic nervous system regulates pancreatic beta-cell proliferation in adult male rats.

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Montreal Diabetes Research Center, CRCHUM, University of Montreal, QC, Canada, Canada.
Montreal Diabetes Research Center, CRCHUM, and Department of Medicine, University of Montreal, QC, Canada, Canada.


The pancreatic beta-cell responds to changes in the nutrient environment to maintain glucose homeostasis by adapting its function and mass. Nutrients can act directly on the beta-cell and also indirectly through the brain via autonomic nerves innervating islets. Despite the importance of the brain-islet axis in insulin secretion, relatively little is known regarding its involvement in beta-cell proliferation. We previously demonstrated that prolonged infusions of nutrients in rats provoke a dramatic increase in beta-cell proliferation in part due to the direct action of nutrients. Here, we addressed the contribution of the autonomic nervous system. In isolated islets, muscarinic stimulation increased, whereas adrenergic stimulation decreased, glucose-induced beta-cell proliferation. Blocking alpha-adrenergic receptors reversed the effect of epinephrine on glucose + non-esterified fatty acids (NEFA)-induced beta-cell proliferation, whereas activation of beta-adrenergic receptors was without effect. Infusion of glucose + NEFA towards the brain stimulated beta-cell proliferation, and this effect was abrogated following coeliac vagotomy. The increase in beta-cell proliferation following peripheral infusions of glucose + NEFA was not inhibited by vagotomy or atropine treatment, but was blocked by co-infusion of epinephrine. We conclude that beta-cell proliferation is stimulated by parasympathetic and inhibited by sympathetic signals. Whereas glucose + NEFA in the brain stimulates beta-cell proliferation through the vagus nerve, beta-cell proliferation in response to systemic nutrient excess does not involve parasympathetic signals but may be associated with decreased sympathetic tone.


Autonomic nervous system; Beta-cell proliferation; Nutrients; Parasympathetic; Sympathetic


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