Nicotinamide mononucleotide promotes pancreatic islet function through the SIRT1 pathway in mice after severe burns.

Abstract

OBJECTIVE:

The high levels of oxidative stress and apoptosis of pancreatic islet cells after severe burns lead to the dysfunction of islets and glucose metabolism disorders. Silent information regulator of transcription 1 (SIRT1) can decrease oxidative stress and apoptosis of islets in diabetes mellitus. This study aimed to investigate the role of SIRT1 on pancreatic islets and whether nicotinamide mononucleotide (NMN) can impact the function of pancreatic islets after severe burns.

METHODS:

A 30% total body surface area full-thickness burn model was established using male C57BL/6 mice, and mice were randomized into sham group, burn group, burn + NMN group and burn + NMN + EX-527 group. The concentration of nicotinamide adenine dinucleotide (NAD), the expression of SIRT1, apoptosis induction, mitochondrial function and related signalling pathways of pancreatic islets at 24 h after severe burns were tested.

RESULTS:

Severe burns led to decreased NAD level and SIRT1 expression of pancreatic islets, increased apoptosis rate, and mitochondrial dysfunction of pancreatic islets. NAD repletion by NMN and upregulation of SIRT1 expression reduced the phosphorylation and acetylation levels of NF-κB p65 and burn-induced apoptosis. Meanwhile, the mitochondrial function of islets was rescued by NMN treatment through the SIRT1/UCP2 axis and SIRT1/PGC1-α axis. In addition, the fasting blood glucose decreased and glucose-stimulated insulin secretion was improved with NMN treatment after severe burns. This protective effect of NMN could be abolished by EX-527, the inhibitor of SIRT1.

CONCLUSION:

NMN can increase the concentration of NAD+ of pancreatic islets and regulate SIRT1 and its downstream targets, thereby reducing apoptosis, maintaining mitochondrial function and improving pancreatic islet function after severe burn injury.

• Authors: Xinzhu Liu, Dawei Li, Zhaoxing Liu, Yaoyao Song, Bohan Zhang, Yu Zang, Wen Zhang, Yuezeng Niu, Chuan'an Shen
• Journal: Burns : journal of the International Society for Burn Injuries (Burns) Vol. 48 Issue 8 Pg. 1922-1932 (12 2022) ISSN: 1879-1409 [Electronic] Netherlands
• PMID: 35123833 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier Ltd.

Chemical References

• Nicotinamide Mononucleotide
• Sirtuin 1
• NAD
• Sirt1 protein, mouse

Topics

• Animals
• Mice
• Male
• Nicotinamide Mononucleotide (pharmacology, metabolism)
• Sirtuin 1 (metabolism)
• NAD (metabolism)
• Burns (metabolism)
• Mice, Inbred C57BL
• Islets of Langerhans (metabolism)