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Emerging Role of PACAP as a New Potential Therapeutic Target in Major Diabetes Complications
Rubina Marzagalli1, Soraya Scuderi1, Filippo Drago2
1Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
Abstract:
Enduring diabetes increases the probability of developing secondary damage to numerous systems, and these complications represent a cause of morbidity and mortality. Establishing the causes of diabetes remains the key step to eradicate the disease, but prevention as well as finding therapies to ameliorate some of the major diabetic complications is an equally important step to increase life expectancy and quality for the millions of individuals already affected by the disease or who are likely to develop it before cures become routinely available. In this review, we will firstly summarize some of the major complications of diabetes, including endothelial and pancreatic islets dysfunction, retinopathy, and nephropathy, and then discuss the emerging roles exerted by the neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) to counteract these ranges of pathologies that are precipitated by the prolonged hyperglycemic state. Finally, we will describe the main signalling routes activated by the peptide and propose possible future directions to focus on developing more effective peptide-based therapies to treat the major complications associated with longstanding diabetes.
Insights
Diabetes complications cause significant harm. This review explores how pituitary adenylate cyclase activating polypeptide (PACAP) may counteract diabetic damage, offering hope for new peptide-based therapies.
Area of Science:
- Endocrinology and metabolic diseases
- Molecular and cellular biology
- Neuropeptide signaling
Background:
- Diabetes mellitus leads to severe systemic complications, contributing to morbidity and mortality.
- Effective management of diabetes requires understanding its causes and developing therapies for its complications.
- Longstanding hyperglycemia precipitates various pathological conditions, impacting multiple organ systems.
Purpose of the Study:
- To review major complications of diabetes, including endothelial dysfunction, pancreatic islet dysfunction, retinopathy, and nephropathy.
- To discuss the potential therapeutic roles of the neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) in mitigating diabetic pathologies.
- To outline signaling pathways activated by PACAP and suggest future directions for peptide-based treatments.
Main Methods:
- Literature review of existing studies on diabetes complications.
- Analysis of research on the neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP).
- Exploration of signaling mechanisms associated with PACAP activity in the context of diabetes.
Main Results:
- Identified key diabetes complications such as retinopathy and nephropathy.
- Highlighted the emerging role of PACAP in potentially counteracting diabetes-induced damage.
- Described signaling pathways modulated by PACAP relevant to diabetic complications.
Conclusions:
- PACAP shows promise as a therapeutic agent against diabetes complications.
- Further research into PACAP signaling pathways can guide the development of novel peptide-based therapies.
- Targeting PACAP may offer a new strategy to improve outcomes for individuals with diabetes.
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