PMID- 34647606
OWN - NLM
STAT- MEDLINE
DCOM- 20220328
LR  - 20220328
IS  - 2299-8306 (Electronic)
IS  - 0423-104X (Linking)
VI  - 72
IP  - 6
DP  - 2021
TI  - Neu-P11 - a novel melatonin receptor agonist, could improve the features of 
      type-2 diabetes mellitus in rats.
PG  - 634-642
LID - 10.5603/EP.a2021.0084 [doi]
AB  - 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 isletbeta 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 factoralpha (TNF-alpha), interleukins 
      IL-10 and IL-1beta, interferongamma (IFN-gamma), 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-alpha and IL-beta 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, 
      isletbeta 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 isletbeta cell function, and this improve the 
      characterization of T2DM-related diseases.
FAU - Li, Xiuping
AU  - Li X
AD  - School of Public Health and Laboratory Medicine, Hunan University of Medicine, 
      Huaihua, China.
FAU - He, Juan
AU  - He J
AD  - Department of Physiology, Hunan University of Medicine, Huaihua, China.
FAU - Li, Xing
AU  - Li X
AD  - School of Basic Medical Sciences, Shaoyang University, Shaoyang, China.
FAU - Li, Yuxian
AU  - Li Y
AD  - Department of Diagnostics, Hunan University of Medicine, Huaihua, China.
FAU - Zhou, Yang
AU  - Zhou Y
AD  - Functional Experimental Centre, Hunan University of Medicine, Huaihua, China.
FAU - Cai, Shichang
AU  - Cai S
AD  - Department of Human Anatomy, School of Medicine, Hunan University of Medicine, 
      Huaihua, China. caishichang_glia@163.com.
LA  - eng
PT  - Journal Article
DEP - 20211014
PL  - Poland
TA  - Endokrynol Pol
JT  - Endokrynologia Polska
JID - 0370674
RN  - 0 (Blood Glucose)
RN  - 0 (C-Peptide)
RN  - 0 (Indoles)
RN  - 0 (Pyrans)
RN  - 0 (Receptors, Melatonin)
RN  - 5W494URQ81 (Streptozocin)
RN  - JL5DK93RCL (Melatonin)
RN  - S3UN2146K9 (N-(2-(5-methoxy-indol-3-yl)-ethyl)-4-oxo-4H-pyran-2-carboxamide)
SB  - IM
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - C-Peptide/blood
MH  - Diabetes Mellitus, Experimental
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Diet, High-Fat
MH  - Disease Models, Animal
MH  - Glycemic Control
MH  - Indoles/*therapeutic use
MH  - Insulin Resistance
MH  - Melatonin/*pharmacology
MH  - Pyrans/*therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Melatonin/*agonists
MH  - Streptozocin/*adverse effects
OTO - NOTNLM
OT  - Neu-P11
OT  - immunity
OT  - melatonin
OT  - type 2 diabetes mellitus
EDAT- 2021/10/15 06:00
MHDA- 2022/03/29 06:00
CRDT- 2021/10/14 08:41
PHST- 2021/06/03 00:00 [received]
PHST- 2021/08/20 00:00 [accepted]
PHST- 2021/08/20 00:00 [revised]
PHST- 2021/10/15 06:00 [pubmed]
PHST- 2022/03/29 06:00 [medline]
PHST- 2021/10/14 08:41 [entrez]
AID - VM/OJS/J/84002 [pii]
AID - 10.5603/EP.a2021.0084 [doi]
PST - ppublish
SO  - Endokrynol Pol. 2021;72(6):634-642. doi: 10.5603/EP.a2021.0084. Epub 2021 Oct 14.