VIP: The Master Conductor of Biological Harmony
When a 28-amino-acid peptide discovered in pig intestines becomes the key to understanding circadian rhythms, immune regulation, and viral defense
There's something almost poetic about the fact that one of the most versatile therapeutic peptides in modern medicine was first discovered while researchers were trying to understand why pig intestines dilated blood vessels. Vasoactive Intestinal Peptide—VIP to those who've spent enough time with it to be on a first-name basis—represents the kind of scientific discovery that makes you question everything you thought you knew about biological specialization. Here's a molecule that was supposed to be about gut function, yet it turns out to orchestrate circadian rhythms, modulate immune responses, protect neurons from degeneration, and even defend against viral infections.
The story of VIP reads less like a traditional pharmaceutical development narrative and more like a detective novel where each new clue reveals that the suspect has been living multiple secret lives. What began in 1970 as Said and Mutt's investigation into intestinal vasodilation has evolved into a research field spanning neuroscience, immunology, endocrinology, and now, as we've learned from 2025 research, virology. It's the kind of scientific journey that reminds us why basic research matters—you never know when your study of pig gut physiology might unlock the secrets of human circadian biology or provide new weapons against pandemic viruses.
Unlike many peptides that excel in one biological domain while remaining mediocre in others, VIP demonstrates what can only be described as biological omnipotence. It's simultaneously a neurotransmitter, a hormone, an immune modulator, a circadian regulator, and an antiviral agent. This isn't the result of evolutionary accident or scientific wishful thinking—it's the product of a molecule that has been refined over millions of years to serve as a master coordinator of biological systems that need to work in harmony.
The more we learn about VIP, the more it becomes clear that we're dealing with something fundamentally different from the typical "one target, one disease" paradigm that dominates modern drug development. VIP operates more like a biological Swiss Army knife, equipped with different tools for different situations but unified by an underlying logic that prioritizes system-wide coordination over local optimization. It's the difference between a specialist who knows everything about one thing and a conductor who knows how to make an entire orchestra sound like music.
The Serendipitous Discovery That Redefined Peptide Biology
The discovery of VIP in 1970 represents one of those beautiful moments in scientific history where researchers set out to answer a simple question and accidentally stumbled onto something far more profound [1]. Said and Mutt were investigating why certain extracts from porcine duodenum caused such dramatic vasodilation—the kind of blood vessel relaxation that makes physiologists sit up and take notice. They weren't looking for a master regulator of biological rhythms or a key player in immune function; they just wanted to understand why pig gut extracts made blood vessels behave in unexpected ways.
The isolation process itself was a masterclass in biochemical detective work. Starting with crude tissue extracts that contained thousands of different molecules, Said and Mutt systematically purified and characterized the active component until they had identified a 28-amino-acid peptide with remarkable biological activity [1]. The peptide they isolated was unlike anything previously described—it was highly basic, single-chained, and demonstrated sequence similarity to secretin, suggesting it belonged to what would later be recognized as the glucagon/secretin superfamily of peptides.
What made the discovery particularly intriguing was the peptide's potency. VIP didn't just cause vasodilation; it caused dramatic, sustained vasodilation at concentrations that barely registered on conventional analytical equipment. This wasn't a weak biological signal that required massive doses to produce effects—this was a molecule that could fundamentally alter cardiovascular physiology at nanomolar concentrations. It was the kind of biological activity that suggested VIP was designed by evolution to be a signaling molecule, not just a metabolic byproduct.
The initial characterization revealed structural features that would prove crucial to understanding VIP's diverse biological activities. The peptide's secondary structure consists of two β-turns containing the initial N-terminal eight amino acid residues, followed by two helices [2]. This structural arrangement creates a molecule that's both stable enough to survive in biological fluids and flexible enough to interact with multiple different receptor types. It's a design that prioritizes functional versatility over structural rigidity—exactly what you'd expect from a molecule that needs to coordinate multiple biological systems.
The C-terminal amidation proved particularly important for biological activity. Unlike many peptides where structural modifications have minimal functional consequences, VIP's amidated C-terminus is essential for receptor binding and biological activity [2]. This structural requirement would later become crucial for developing synthetic VIP analogs and understanding structure-activity relationships. It's the kind of molecular detail that seems trivial until you realize it's the difference between a therapeutically active compound and an expensive collection of amino acids.
Perhaps most remarkably, the discovery of VIP's sequence similarity to secretin provided the first hint that this wasn't just another gut peptide. The glucagon/secretin superfamily includes some of the most important regulatory peptides in mammalian physiology, suggesting that VIP was likely to have functions far beyond intestinal vasodilation. It was like discovering that your new neighbor, who you thought was just a plumber, actually holds advanced degrees in engineering, medicine, and theoretical physics.
The Molecular Architecture of Systemic Coordination
Understanding how VIP works requires appreciating the elegant sophistication of its receptor system. Unlike peptides that rely on a single receptor type to mediate their effects, VIP operates through a carefully orchestrated network of three distinct G protein-coupled receptors: VPAC1, VPAC2, and PAC1 [3]. This multi-receptor system allows VIP to produce tissue-specific effects while maintaining system-wide coordination—like having different keys for different rooms in the same building, but with a master key that can access the building's central control systems.
The VPAC1 and VPAC2 receptors show high affinity for both VIP and its close relative PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide), while the PAC1 receptor is selective for PACAP with lower affinity for VIP [3]. This receptor distribution creates a sophisticated signaling network where VIP can produce both overlapping and distinct effects depending on the tissue context and receptor expression patterns. It's the kind of molecular architecture that allows for both broad systemic effects and precise local control.
The intracellular signaling cascades triggered by VIP receptor activation reveal why this peptide can coordinate such diverse biological functions. When VIP binds to VPAC2 receptors, it triggers a G-alpha-mediated signaling cascade that activates adenylyl cyclase, leading to increases in cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) activation [3]. The PKA then phosphorylates CREB and other transcriptional factors, ultimately leading to the activation of gene expression pathways including the circadian clock genes Per1 and Per2.
This cAMP-PKA-CREB pathway is particularly important for understanding VIP's role in circadian rhythm regulation. The mPer1 and mPer2 promoters contain cAMP response elements (CRE), providing a direct molecular mechanism for VIP to regulate the molecular clock itself [3]. It's not just that VIP affects circadian rhythms—it's that VIP directly controls the transcriptional machinery that generates circadian rhythms. This is the difference between adjusting the hands on a clock and actually controlling the mechanism that makes the clock tick.
The co-release of VIP with GABA adds another layer of complexity to its signaling mechanisms. GABA levels are connected to VIP function, and sparse GABAergic connections are thought to decrease synchronized firing in the suprachiasmatic nucleus [3]. While GABA controls the amplitude of SCN neuronal rhythms, it's not critical for maintaining synchrony. However, the dynamic nature of GABA release may mask or amplify the synchronizing effects of VIP, creating a sophisticated regulatory system that can fine-tune circadian coordination based on environmental and physiological conditions.
The tissue distribution of VIP receptors provides insight into the peptide's diverse biological functions. VPAC2 receptors are particularly abundant in the ventrolateral aspect of the suprachiasmatic nucleus, the region that receives retinal information from the retinohypothalamic tract [3]. This anatomical arrangement positions VIP as a crucial link between environmental light cues and the body's internal circadian machinery. It's like having a molecular translator that can convert light signals into the biochemical language of circadian rhythms.
The short half-life of VIP in circulation—approximately two minutes—initially seems like a disadvantage but actually reflects sophisticated evolutionary optimization [1]. A signaling molecule that needs to coordinate rapid responses to environmental changes can't afford to linger in the system long after the signal has ended. The brief half-life ensures that VIP's effects are temporally precise, allowing for rapid adjustments to changing conditions without creating persistent biological noise that might interfere with subsequent signaling events.
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The Circadian Command Center: VIP's Role in Biological Timekeeping
Perhaps no aspect of VIP biology is more fascinating than its central role in mammalian circadian rhythm regulation. The suprachiasmatic nucleus (SCN) of the hypothalamus serves as the body's master circadian pacemaker, and VIP functions as the primary synchronizing agent among SCN neurons [3]. This isn't just another biological function that VIP happens to influence—it's a fundamental role that positions VIP as one of the most important molecules in mammalian temporal biology.
The SCN coordinates daily timekeeping throughout the body, and VIP plays a crucial role in communication between individual brain cells within this region. At the cellular level, the SCN expresses different electrical activity patterns in circadian time, with higher activity observed during the day and lower activity during the night [3]. This rhythm is thought to be an important feature that allows SCN neurons to synchronize with each other and control rhythmicity in other brain regions. VIP serves as the molecular messenger that maintains this synchronization.
The anatomical organization of VIP-containing neurons within the SCN reveals the sophisticated architecture of circadian control. The high concentration of VIP and VIP receptor-containing neurons are primarily found in the ventrolateral aspect of the SCN, which is located above the optic chiasm [3]. This positioning is not coincidental—the neurons in this area receive retinal information from the retinohypothalamic tract and then relay environmental light information to the rest of the SCN. VIP essentially serves as the molecular interface between the external light-dark cycle and the body's internal circadian machinery.
The mechanism by which VIP synchronizes circadian rhythms involves both direct neuronal communication and paracrine signaling. The leading hypothesis suggests that VIP-expressing neurons use the peptide to communicate with specific postsynaptic targets, regulating circadian rhythm through precise temporal control of gene expression [3]. When light depolarizes VIP-expressing neurons, it causes the release of VIP and co-transmitters (including GABA) that can alter the properties of downstream neurons through VPAC2 receptor activation. This creates a cascade of molecular events that ultimately resets the circadian clock to match environmental conditions.
The importance of VIP in circadian function becomes dramatically apparent in VIP-deficient mice. Animals lacking either VIP or VIP receptors show severely compromised circadian rhythms, with reduced ability to maintain synchronized oscillations and impaired responses to light cues [3]. The population synchrony that characterizes normal SCN function is lost, and individual cells struggle to generate coherent oscillations. It's like trying to coordinate a symphony orchestra without a conductor—the individual musicians might be capable, but the collective performance falls apart without central coordination.
Recent research has revealed that VIP's circadian effects extend far beyond simple timekeeping. The peptide appears to coordinate the timing of multiple physiological processes, ensuring that different biological systems operate in harmony with each other and with environmental conditions. This includes regulation of hormone secretion, body temperature, metabolism, and immune function—essentially creating a temporal framework that optimizes biological efficiency across multiple domains.
The clinical implications of VIP's circadian functions are profound. Circadian rhythm disruption is associated with numerous health problems, including metabolic disorders, immune dysfunction, cardiovascular disease, and neurodegeneration. Understanding VIP's role in circadian regulation opens new therapeutic possibilities for treating conditions related to biological timing disruption. It's not just about fixing broken clocks—it's about restoring the temporal coordination that underlies healthy biological function.
The relationship between VIP and circadian rhythms also provides insight into why this peptide demonstrates such broad biological activity. Many of VIP's diverse functions—immune modulation, metabolic regulation, cardiovascular effects—show circadian variation. By serving as a master coordinator of biological timing, VIP ensures that these different physiological systems operate in temporal harmony. It's the difference between having multiple biological processes running independently and having them orchestrated as part of a coordinated biological symphony.
The Immune System's Diplomatic Corps
VIP's role in immune regulation represents one of the most clinically promising aspects of its biology, demonstrating how a single peptide can serve as a master coordinator of inflammatory responses while promoting tissue repair and regeneration. Unlike traditional anti-inflammatory drugs that often work by broadly suppressing immune function, VIP operates more like a sophisticated diplomatic corps, selectively modulating immune responses to promote resolution of inflammation while maintaining protective immunity.
The peptide's immune-modulating effects are mediated through direct actions on multiple immune cell types, including T cells, B cells, macrophages, dendritic cells, and mast cells [4]. VIP consistently suppresses the release of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β while promoting the production of anti-inflammatory mediators and enhancing regulatory T-cell function. This isn't simply immune suppression—it's immune rebalancing, shifting the system from a pro-inflammatory state toward resolution and repair.
The mechanism behind VIP's anti-inflammatory effects involves multiple pathways, but one of the most important appears to be the modulation of transcription factors that control inflammatory gene expression. VIP treatment consistently reduces NF-κB activation, a key transcriptional regulator of inflammatory responses, while promoting the activation of anti-inflammatory transcription factors [4]. This creates a coordinated shift in gene expression patterns that favors resolution of inflammation over its perpetuation.
Recent research has revealed that VIP's immune effects extend beyond simple anti-inflammatory activity to include direct antimicrobial properties. The 2025 COVID-19 study demonstrated that VIP can reduce viral infection by downregulating the expression of viral entry receptors ACE2 and TMPRSS2 while simultaneously promoting their shedding from cell surfaces through ADAM10 activation [5]. This dual mechanism—reducing receptor expression and promoting receptor shedding—provides a sophisticated antiviral defense that doesn't rely on traditional immune activation.
The clinical implications of VIP's antiviral properties became particularly relevant during the COVID-19 pandemic. Clinical trials investigating VIP treatment in critically ill COVID-19 patients found that higher plasma VIP levels correlated with improved survival rates, and intravenous VIP administration showed promise for improving outcomes in respiratory failure [5]. The peptide's ability to simultaneously modulate immune responses and interfere with viral entry mechanisms positions it as a unique therapeutic approach for viral infections.
VIP's effects on inflammatory bowel disease (IBD) demonstrate the peptide's potential for treating chronic inflammatory conditions. Experimental studies have consistently shown that VIP administration can effectively inhibit experimental colitis in mice, reducing clinical and histopathologic severity while promoting mucosal healing [6]. The peptide works through multiple mechanisms, including direct anti-inflammatory effects on intestinal epithelial cells, modulation of immune cell function, and promotion of tissue repair processes.
The therapeutic advantage of VIP in IBD lies in its ability to address multiple aspects of the disease simultaneously. Rather than simply suppressing inflammation, VIP promotes the restoration of normal intestinal barrier function, reduces oxidative stress, and enhances the body's natural repair mechanisms [6]. This comprehensive approach addresses the underlying pathophysiology of IBD rather than just managing symptoms, potentially offering better long-term outcomes than traditional therapies.
The development of VIP-based nanomedicine formulations has addressed one of the major challenges in translating VIP's therapeutic potential to clinical applications. The peptide's short half-life in circulation has historically limited its clinical utility, but advanced delivery systems including nanoparticle encapsulation and sustained-release formulations have dramatically improved its pharmacokinetic properties [7]. These technological advances make it possible to achieve therapeutic VIP concentrations for extended periods, opening new possibilities for clinical applications.
The safety profile of VIP in clinical studies has been remarkably favorable, with minimal adverse effects reported even at therapeutic doses [7]. This safety profile, combined with the peptide's natural occurrence in human physiology, makes VIP an attractive candidate for therapeutic development. Unlike synthetic drugs that often produce off-target effects, VIP works through endogenous pathways that the body is already equipped to handle.
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Neurological Renaissance: VIP's Neuroprotective Promise
The neuroprotective properties of VIP represent one of the most exciting frontiers in peptide therapeutics, offering hope for treating neurodegenerative diseases that have proven resistant to conventional therapeutic approaches. VIP's ability to protect neurons from damage, reduce neuroinflammation, and promote neural repair positions it as a potential game-changer in the treatment of conditions like Alzheimer's disease, Parkinson's disease, and stroke.
The mechanisms underlying VIP's neuroprotective effects are multifaceted and sophisticated. The peptide directly protects neurons from excitotoxic damage, reduces oxidative stress, and promotes the survival of damaged neural tissue [8]. VIP also modulates microglial activation, shifting these brain immune cells from a pro-inflammatory phenotype toward a repair-promoting phenotype. This dual action—direct neuroprotection combined with immune modulation—creates a comprehensive approach to neural preservation and repair.
Research in Alzheimer's disease models has demonstrated particularly promising results. VIP administration has been shown to preserve cognitive function, reduce amyloid plaque formation, and protect synaptic integrity in multiple preclinical studies [8]. The peptide appears to work through several mechanisms, including reduction of neuroinflammation, enhancement of amyloid clearance, and direct protection of synaptic connections. These effects address multiple aspects of Alzheimer's pathophysiology simultaneously, potentially offering advantages over single-target therapeutic approaches.
The relationship between VIP and circadian rhythm disruption in neurodegenerative diseases adds another dimension to its therapeutic potential. Many neurodegenerative conditions are associated with disrupted sleep-wake cycles and circadian dysfunction, which can accelerate disease progression and worsen cognitive symptoms [9]. VIP's dual role as both a neuroprotective agent and a circadian regulator positions it uniquely to address both the primary pathology and the secondary complications of neurodegenerative diseases.
Clinical translation of VIP's neuroprotective properties faces several challenges, primarily related to drug delivery and stability. The blood-brain barrier limits the penetration of many peptides into brain tissue, and VIP's short half-life requires sophisticated delivery systems to achieve therapeutic concentrations in neural tissue [10]. However, recent advances in peptide modification, including the development of stapled VIP analogs and advanced delivery systems, are beginning to address these limitations.
The potential for combination therapies represents another promising avenue for VIP-based neuroprotection. The peptide's broad mechanism of action makes it an ideal candidate for combination with other neuroprotective agents, potentially creating synergistic effects that exceed what either therapy could achieve alone [10]. This approach could be particularly valuable in complex neurodegenerative diseases where multiple pathological processes contribute to disease progression.
The safety profile of VIP in neurological applications appears favorable based on preclinical studies, with minimal adverse effects reported even with chronic administration [10]. This safety profile, combined with the peptide's natural occurrence in brain tissue, suggests that VIP-based therapies could offer a gentler alternative to more aggressive neuroprotective interventions that often produce significant side effects.
Metabolic Mastery: VIP's Role in Glucose Homeostasis
VIP's emerging role in metabolic regulation, particularly in diabetes management, represents one of the most clinically advanced applications of this versatile peptide. The discovery that VIP can stimulate glucose-dependent insulin secretion has opened new therapeutic possibilities for treating type 2 diabetes while avoiding the hypoglycemic risks associated with traditional insulin secretagogues [11].
The mechanism by which VIP regulates glucose homeostasis is elegantly designed to provide therapeutic benefit without compromising safety. VIP stimulates insulin secretion primarily through binding to VPAC2 receptors on pancreatic beta cells, but this effect is strictly glucose-dependent [11]. When blood glucose levels are normal or low, VIP has minimal effect on insulin release. However, when glucose levels are elevated, VIP dramatically enhances insulin secretion, helping to restore normal glucose homeostasis.
This glucose-dependent mechanism represents a significant advantage over traditional diabetes medications that can cause dangerous hypoglycemic episodes. VIP essentially acts as a smart insulin secretagogue, providing therapeutic benefit when needed while remaining inactive when blood glucose levels are appropriate [11]. It's the kind of sophisticated biological regulation that pharmaceutical companies spend billions trying to replicate with synthetic drugs.
The development of modified VIP analogs has addressed many of the practical challenges associated with using native VIP as a diabetes therapy. Stapled VIP derivatives show improved stability and enhanced glucose-dependent insulin secretion compared to the native peptide [12]. These modifications maintain the peptide's therapeutic activity while dramatically improving its pharmacokinetic properties, making clinical development more feasible.
Clinical studies of VIP-based diabetes therapies have shown promising results, with improved glucose control and minimal adverse effects reported in early-phase trials [11]. The peptide's natural occurrence in human physiology and its glucose-dependent mechanism of action contribute to a favorable safety profile that could make it an attractive option for patients who cannot tolerate existing diabetes medications.
The potential for VIP in diabetes extends beyond simple glucose control to include effects on diabetic complications. The peptide's anti-inflammatory and tissue-protective properties could help prevent or treat diabetic complications such as nephropathy, neuropathy, and retinopathy [13]. This comprehensive approach to diabetes management—addressing both glucose control and complications prevention—represents a significant advance over therapies that focus solely on glycemic control.
The integration of VIP-based therapies with existing diabetes treatments offers additional therapeutic possibilities. The peptide's unique mechanism of action makes it compatible with most existing diabetes medications, potentially allowing for combination therapies that provide superior glucose control with reduced side effects [11]. This flexibility could be particularly valuable for patients with complex diabetes management needs.
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The Future of VIP: From Laboratory Curiosity to Clinical Reality
The trajectory of VIP research over the past five decades illustrates how basic scientific discovery can evolve into transformative therapeutic applications. What began as an investigation into pig intestinal physiology has become a comprehensive understanding of one of the most versatile regulatory peptides in mammalian biology. The challenge now is translating this scientific knowledge into clinical therapies that can benefit patients across multiple disease areas.
The most significant obstacle to VIP's clinical development has been its short half-life in circulation, but recent advances in peptide modification and drug delivery are rapidly addressing this limitation. Stapled peptide analogs, nanoparticle formulations, and sustained-release delivery systems are all showing promise for extending VIP's therapeutic activity while maintaining its biological specificity [14]. These technological advances are making it possible to achieve therapeutic VIP concentrations for clinically relevant periods.
The regulatory pathway for VIP-based therapies is becoming clearer as clinical data accumulates. The peptide's natural occurrence in human physiology and its favorable safety profile in early clinical studies provide a foundation for regulatory approval [14]. Unlike novel synthetic compounds that require extensive safety testing, VIP benefits from decades of research demonstrating its safety and biological activity in human systems.
The market potential for VIP-based therapies is substantial, spanning multiple therapeutic areas including metabolic disorders, inflammatory diseases, neurodegeneration, and infectious diseases. The peptide's broad mechanism of action and favorable safety profile make it an attractive candidate for pharmaceutical development, particularly in areas where existing therapies have significant limitations or side effects [14].
The most exciting prospect may be the development of personalized VIP therapies based on individual patient characteristics. Genetic variations in VIP receptors, circadian rhythm patterns, and metabolic profiles could all influence therapeutic response, opening possibilities for precision medicine approaches that optimize treatment for individual patients [15]. This personalized approach could maximize therapeutic benefit while minimizing adverse effects.
The future of VIP research will likely focus on understanding the peptide's role in aging and longevity. Given VIP's involvement in circadian regulation, immune function, metabolic control, and neuroprotection—all processes that decline with age—there's growing interest in whether VIP-based interventions could promote healthy aging or extend healthspan [15]. This represents the ultimate expression of VIP's biological versatility: not just treating disease, but promoting optimal health across the lifespan.
The story of VIP reminds us that the most important scientific discoveries often come from unexpected directions. A peptide discovered in pig intestines has become a key to understanding circadian biology, immune regulation, and viral defense. It's a reminder that in biology, as in life, the most interesting stories often begin with the phrase "we were studying something completely different when we noticed..."
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References
[1] Vasoactive intestinal peptide - Wikipedia. https://en.wikipedia.org/wiki/Vasoactive_intestinal_peptide
[2] Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC3883350/
[3] Recent advances in vasoactive intestinal peptide physiology and pathophysiology. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC6743256/
[4] The neuropeptide vasoactive intestinal peptide: direct effects on immune cells. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC4484298/
[5] Vasoactive Intestinal Peptide (VIP) in COVID-19 Therapy—Shedding of ACE2 and TMPRSS2 via ADAM10. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC11942504/
[6] Research advances of vasoactive intestinal peptide in the treatment of ulcerative colitis. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC7789055/
[7] Vasoactive Intestinal Peptide Nanomedicine for the Management of Inflammatory Bowel Disease. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC6053281/
[8] The potential of VIP/PACAP in Alzheimer's disease treatment. ScienceDirect. https://www.sciencedirect.com/science/article/pii/S2590262824000807
[9] From circadian sleep disruption to Neuroprotection: The potential of VIP/PACAP. DOAJ. https://doaj.org/article/92c080f99e3b4298906b9b12497cc002
[10] Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide and VIP. Frontiers. https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2020.00221/full
[11] Therapeutic potential of vasoactive intestinal peptide and its receptor VPAC2 in type 2 diabetes. Frontiers. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.984198/full
[12] Stapled Vasoactive Intestinal Peptide (VIP) Derivatives Improve VPAC2 Agonism. ACS Publications. https://pubs.acs.org/doi/abs/10.1021/ml400257h
[13] Involvement of Vasoactive Intestinal Peptide Family Members in Diabetic Keratopathy. MDPI. https://www.mdpi.com/2076-3417/14/5/1754
[14] Therapeutic peptides: current applications and future directions. Nature. https://www.nature.com/articles/s41392-022-00904-4
[15] More Than Three Decades After Discovery of the Neuroprotective Effects of PACAP. Springer. https://link.springer.com/article/10.1007/s12031-025-02366-z