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Updated: Jul 14, 2026

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Published on: January 9, 2026
Role of VIP and PACAP in islet function
Maria Sörhede Winzell1, Bo Ahrén
1Department of Clinical Sciences, Division of Medicine, Lund University, BMC, B11, SE-221 84 Lund, Sweden. Maria.Sorhede_Winzell@med.lu.se
Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are key neuropeptides regulating insulin and glucagon secretion. Their receptors, particularly VPAC2, show therapeutic potential for type 2 diabetes.
Area of Science:
- Endocrinology
- Neuroscience
- Molecular Biology
Background:
- Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are closely related neuropeptides found in pancreatic islets and parasympathetic nerves.
- Both VIP and PACAP bind to G-protein-coupled receptors VPAC1 and VPAC2, while PACAP also binds to the specific PAC1 receptor, all expressed in islets.
Purpose of the Study:
- To review the current understanding of VIP and PACAP roles in pancreatic islet function.
- To explore the potential of VIP and PACAP receptor activation as a therapeutic strategy for type 2 diabetes.
Main Methods:
- This review synthesizes existing research on VIP and PACAP signaling pathways in pancreatic islets.
- Analysis of studies involving receptor deletion (PAC1, VPAC2) and their impact on glucose metabolism.
Main Results:
- VIP and PACAP stimulate insulin and glucagon secretion in a glucose-dependent manner via cAMP production and calcium uptake.
- Deletion of PAC1 or VPAC2 receptors leads to glucose intolerance.
- Animal studies suggest VPAC2 receptor activation may be a therapeutic target for type 2 diabetes.
Conclusions:
- VIP and PACAP play significant roles in prandial insulin secretion and the counter-regulatory glucagon response to hypoglycemia.
- Targeting VIP/PACAP receptors, especially VPAC2, holds promise for novel type 2 diabetes treatments.
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