Abstract
Objective
This study aims to explore the impact of Nesfatin-1 on type 2 diabetic erectile dysfunction (T2DMED) and its underlying mechanism in regulating the phenotypic switching of corpus cavernosum smooth muscle cells (CCSMCs).
Methods
Twenty-four 4-week-old male C57 wild-type mice were randomly assigned to the control group, model group, and Nesfatin-1 treatment group. Monitoring included body weight, blood glucose levels, and penile cavernous pressure (ICP). Histochemistry and Western blot analyses were conducted to assess the expressions of α-SMA, OPN, and factors related to the PI3K/AKT/mTOR signaling pathway. CCSMCs were categorized into the control group, high glucose and high oleic acid group (GO group), Nesfatin-1 treatment group (GO+N group), sildenafil positive control group (GO+S group), and PI3K inhibitor group (GO+N+E group). Changes in phenotypic markers, cell morphology, and the PI3K/AKT/mTOR signaling pathway were observed in each group.
Results
(1) Nesfatin-1 significantly ameliorated the body size, body weight, blood glucose, glucose tolerance, and insulin resistance in T2DMED mice. (2) Following Nesfatin-1 treatment, the ICP/MSBP ratio and the peak of the ICP curve demonstrated a significant increase. (3) Nesfatin-1 significantly enhanced smooth muscle and reduced collagen fibers in the corpus cavernosum. (4) Nesfatin-1 notably increased α-SMA expression and decreased OPN expression in CCSMCs. (5) Nesfatin-1 elevated PI3K, p-AKT/AKT, and p-mTOR/mTOR levels in penile cavernous tissue.
Conclusions
Nesfatin-1 not only effectively improves body weight and blood glucose levels in diabetic mice but also enhances erectile function and regulates the phenotypic switching of corpus cavernosum smooth muscle. The potential mechanism involves Nesfatin-1 activating the PI3K/AKT/mTOR signaling pathway to induce the conversion of CCSMCs to a contractile phenotype.
Funder
National Natural Science Foundation of China
Ningxia Key Research and Development Project
Ningxia Natural Science Foundation
Ningxia science and technology innovation leading talent training project
,Ningxia Medical University research project
Publisher
Public Library of Science (PLoS)
Reference41 articles.
1. Erectile Dysfunction in Diabetes Mellitus;L. S. Malavige;J SEX MED,2009
2. Erectile Dysfunction in General Medicine Practice: Prevalence and Clinical Correlates;K. K. Chew;INT J IMPOT RES,2000
3. The Role of Diabetes Mellitus in Sexual and Reproductive Health: An Overview of Pathogenesis, Evaluation, and Management;J. Gandhi;CURR DIABETES REV,2017
4. [Exogenous Hydrogen Sulfide Improves Erectile Dysfunction by Inhibiting Apoptosis of Corpus Cavernosum Smooth Muscle Cells in Rats with Cavernous Nerve Injury;Q. Zeng;Nan Fang Yi Ke Da Xue Xue Bao,2019
5. The Protective Effect of Salidroside On Hypoxia-Induced Corpus Cavernosum Smooth Muscle Cell Phenotypic Transformation;X. Zhang;EVID-BASED COMPL ALT,2017