open access

Vol 72, No 6 (2021)
Original paper
Submitted: 2021-06-03
Accepted: 2021-08-20
Published online: 2021-10-06
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Neu-P11 — a novel melatonin receptor agonist, could improve the features of type-2 diabetes mellitus in rats

Xiuping Li1, Juan He2, Xing Li3, Yuxian Li4, Yang Zhou5, Shichang Cai6
·
Pubmed: 34647606
·
Endokrynol Pol 2021;72(6):634-642.
Affiliations
  1. School of Public Health and Laboratory Medicine, Hunan University of Medicine, Huaihua, China
  2. Department of Physiology, Hunan University of Medicine, Huaihua, China
  3. School of Basic Medical Sciences, Shaoyang University, Shaoyang, China
  4. Department of Diagnostics, Hunan University of Medicine, Huaihua, China
  5. Functional Experimental Centre, Hunan University of Medicine, Huaihua, China
  6. Department of Human Anatomy, School of Medicine, Hunan University of Medicine, Huaihua, China

open access

Vol 72, No 6 (2021)
Original Paper
Submitted: 2021-06-03
Accepted: 2021-08-20
Published online: 2021-10-06

Abstract

Introduction: Melatonin (Mel) and its receptors are promising for glycaemic control in patients with type 2 diabetes mellitus (T2DM) and its complications, but there is significant heterogeneity among studies. This study aims to investigate the effects of Mel receptor agonist Neu-P11 on glucose metabolism, immunity, and islet function in T2DM rats.

Material and methods: In this study, SD rats were treated with a high-fat diet and streptozotocin (STZ) to establish a T2DM model. The glucose oxidase method was used to measure blood glucose levels. Glucose and insulin tolerance tests were used to assess glucose metabolism. Haematoxylin-eosin staining was used to observe pancreatic tissue injury. The apoptosis of islet β cells was analysed by TUNEL and insulin staining. Reactive oxygen species (ROS) levels and immune cell expression were analysed by flow cytometry. IF was used to analyse the activation of microglia. The immunoglobulins: IgA, IgG, IgM, tumour necrosis factor α (TNF-α), interleukins IL-10 and IL-1β, interferon γ (IFN-γ), C-peptide, and insulin levels were determined by ELISA. The expression of CD11b, CD86, cleaved caspase 3, p21, and P16 proteins were analysed by western blot.

Results: The results showed that the blood glucose level increased, insulin resistance occurred, spleen coefficient and ROS levels increased, humoral immunity in peripheral blood decreased, and inflammation increased in the model group compared to the control group. After Mel and Neu-P11 treatment, the blood glucose level decreased significantly, insulin sensitivity improved, spleen coefficient and ROS levels decreased, humoral immunity in peripheral blood was enhanced, and inflammation improved in T2DM rats. Brain functional analysis of T2DM rats showed that microglia cells were activated, TNF-α and IL-β levels were increased, and IL-10 levels were decreased. Mel and Neu-P11 treatment reversed these indexes. Functional analysis of islets in T2DM rats showed that islet structure inflammation was impaired, islet β cells were apoptotic, p21 and p16 protein expressions were increased, and blood C-peptide and insulin were decreased.
Mel and Neu-P11 treatment restored the function of pancreatic b cells and improved the damage of pancreatic tissue.

Conclusion: Melatonin and its receptor Neu-P11 can reduce the blood glucose level, enhance humoral and cellular immunity, inhibit microglia activation and inflammation, and repair islet β cell function, and this improve the characterization of T2DM-related diseases.

Abstract

Introduction: Melatonin (Mel) and its receptors are promising for glycaemic control in patients with type 2 diabetes mellitus (T2DM) and its complications, but there is significant heterogeneity among studies. This study aims to investigate the effects of Mel receptor agonist Neu-P11 on glucose metabolism, immunity, and islet function in T2DM rats.

Material and methods: In this study, SD rats were treated with a high-fat diet and streptozotocin (STZ) to establish a T2DM model. The glucose oxidase method was used to measure blood glucose levels. Glucose and insulin tolerance tests were used to assess glucose metabolism. Haematoxylin-eosin staining was used to observe pancreatic tissue injury. The apoptosis of islet β cells was analysed by TUNEL and insulin staining. Reactive oxygen species (ROS) levels and immune cell expression were analysed by flow cytometry. IF was used to analyse the activation of microglia. The immunoglobulins: IgA, IgG, IgM, tumour necrosis factor α (TNF-α), interleukins IL-10 and IL-1β, interferon γ (IFN-γ), C-peptide, and insulin levels were determined by ELISA. The expression of CD11b, CD86, cleaved caspase 3, p21, and P16 proteins were analysed by western blot.

Results: The results showed that the blood glucose level increased, insulin resistance occurred, spleen coefficient and ROS levels increased, humoral immunity in peripheral blood decreased, and inflammation increased in the model group compared to the control group. After Mel and Neu-P11 treatment, the blood glucose level decreased significantly, insulin sensitivity improved, spleen coefficient and ROS levels decreased, humoral immunity in peripheral blood was enhanced, and inflammation improved in T2DM rats. Brain functional analysis of T2DM rats showed that microglia cells were activated, TNF-α and IL-β levels were increased, and IL-10 levels were decreased. Mel and Neu-P11 treatment reversed these indexes. Functional analysis of islets in T2DM rats showed that islet structure inflammation was impaired, islet β cells were apoptotic, p21 and p16 protein expressions were increased, and blood C-peptide and insulin were decreased.
Mel and Neu-P11 treatment restored the function of pancreatic b cells and improved the damage of pancreatic tissue.

Conclusion: Melatonin and its receptor Neu-P11 can reduce the blood glucose level, enhance humoral and cellular immunity, inhibit microglia activation and inflammation, and repair islet β cell function, and this improve the characterization of T2DM-related diseases.

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Keywords

melatonin; Neu-P11; type 2 diabetes mellitus; immunity

About this article
Title

Neu-P11 — a novel melatonin receptor agonist, could improve the features of type-2 diabetes mellitus in rats

Journal

Endokrynologia Polska

Issue

Vol 72, No 6 (2021)

Article type

Original paper

Pages

634-642

Published online

2021-10-06

Page views

7077

Article views/downloads

670

DOI

10.5603/EP.a2021.0084

Pubmed

34647606

Bibliographic record

Endokrynol Pol 2021;72(6):634-642.

Keywords

melatonin
Neu-P11
type 2 diabetes mellitus
immunity

Authors

Xiuping Li
Juan He
Xing Li
Yuxian Li
Yang Zhou
Shichang Cai

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