# Protective Effects of PACAP in Diabetic Complications: Retinopathy, Nephropathy and Neuropathy

## TL;DR

This review explores how PACAP, a neuropeptide, protects against various complications of diabetes, including retinopathy, nephropathy, and neuropathy.

## Contribution

The paper provides a comprehensive summary of PACAP's protective effects in major diabetic complications and highlights its potential as a therapeutic agent.

## Key findings

- PACAP counteracts retinal degeneration and inhibits apoptosis in diabetic retinopathy models.
- PACAP improves kidney morphology and reduces fibrosis in diabetic nephropathy.
- PACAP protects against axonal-myelin lesions in diabetic neuropathy.

## Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide exerting, among others, strong trophic and protective effects. It plays a role in several physiological functions, including glucose homeostasis. The protective effects of PACAP are mainly mediated via its specific PAC1 receptor by stimulating anti-inflammatory, anti-apoptotic and antioxidant pathways. The aim of the present review is to summarize data on the protective effects of PACAP in the three major complications of diabetes, retinopathy, nephropathy and neuropathy, as well as some other complications. In type 1 and type 2 diabetic retinopathy models and in glucose-exposed cells of the eye, PACAP counteracted the degeneration of retinal layers and inhibited apoptosis and factors leading to abnormal vessel growth. In models of nephropathy, kidney morphology was better retained after PACAP administration, with decreased apoptosis and fibrosis. In diabetic neuropathy, PACAP protected against axonal–myelin lesions and less activation in pain processing centers. This neuropeptide has several other beneficial effects in diabetes-induced complications like altered vascular response, cognitive deficits and atherosclerosis. The promising therapeutic effects of PACAP in several pathological conditions have encouraged researchers to design PACAP-related drugs and to develop ways to enhance tissue delivery. These intentions are expected to result in overcoming the hurdles preventing PACAP from being introduced into therapeutic treatments, including diabetes-related conditions.