PMID- 32266256
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220413
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 8
DP  - 2020
TI  - Dynamic Phenotypes and Molecular Mechanisms to Understand the Pathogenesis of 
      Diabetic Nephropathy in Two Widely Used Animal Models of Type 2 Diabetes 
      Mellitus.
PG  - 172
LID - 10.3389/fcell.2020.00172 [doi]
LID - 172
AB  - OBJECTIVE: We aimed to characterize the pathogenesis of diabetic nephropathy (DN) 
      in two commonly used type 2 diabetes mellitus (T2DM) animal models and explore 
      the preliminary molecular mechanisms underlying DN in two models. METHODS: To 
      verify the effect of hyperglycemia on renal tissue, we observed the cell growth 
      inhibition rate by adding different concentration of glucose to cell supernatant. 
      After that, a chemically-induced T2DM model was established by administering 
      streptozotocin (STZ) to Sprague Dawley (SD) rats in combination with high fat 
      feeding. In addition, a spontaneous T2DM model was established by feeding 8 weeks 
      old KK-Ay mice a high-fat diet during a period of over 20 weeks. Animal body 
      weight, fasting blood glucose (FBG), insulin tolerance, lipid metabolism, renal 
      function, and renal pathology were periodically measured (once every 2 or 4 
      weeks) over a duration of 20 weeks. At the 12th week, an Affymetrix gene chip 
      assay was performed on the renal tissues extracted from the T2DM animal models 
      and control animals. Through screening for the differentially expressed genes, 
      some key genes were selected for PCR validation. RESULTS: High level of glucose 
      could inhibit the growth of kidney cells. Besides, KK-Ay mice were found to have 
      high FBG and abnormal insulin tolerance. Renal dysfunction and pathology were 
      observed at the 4th week following the start of model creation, which increased 
      in severity over the length of the experiment. The T2DM SD rats also showed high 
      FBG, abnormal glucose tolerance and abnormal lipid metabolism, but the renal 
      function and renal pathology changed only slightly within 20 weeks. Gene 
      profiling in animal kidneys and subsequent analyses and validation revealed 
      differentially expressed genes and enriched pathways in DN. CONCLUSION: KK-Ay 
      mice with both high fasting glucose and insulin resistance were more likely to 
      develop diabetic nephropathy than STZ-induced diabetic SD rats with low fasting 
      glucose or only insulin resistance. The KK-Ay mice model showed earlier onset of 
      the typical pathological characteristics associated with T2DM and obvious renal 
      lesions suggestive of kidney damage.
CI  - Copyright (c) 2020 Liu, Huang, Gao and Liu.
FAU - Liu, Yanfei
AU  - Liu Y
AD  - Cardiovascular Diseases Center, Xiyuan Hospital of China Academy of Chinese 
      Medical Sciences, Beijing, China.
AD  - Graduate School, Beijing University of Chinese Medicine, Beijing, China.
AD  - Institute of Clinical Pharmacology of Xiyuan Hospital, China Academy of Chinese 
      Medical Sciences, Beijing, China.
FAU - Huang, Hui
AU  - Huang H
AD  - Beijing Duan-Dian Pharmaceutical Research & Development Co., Ltd., Beijing, 
      China.
FAU - Gao, Rui
AU  - Gao R
AD  - Institute of Clinical Pharmacology of Xiyuan Hospital, China Academy of Chinese 
      Medical Sciences, Beijing, China.
FAU - Liu, Yue
AU  - Liu Y
AD  - Cardiovascular Diseases Center, Xiyuan Hospital of China Academy of Chinese 
      Medical Sciences, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20200319
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC7098383
OTO - NOTNLM
OT  - KK-Ay mice
OT  - diabetic nephropathy
OT  - pathogenesis
OT  - sprague dawley rat
OT  - type 2 diabetes mellitus
EDAT- 2020/04/09 06:00
MHDA- 2020/04/09 06:01
PMCR- 2020/01/01
CRDT- 2020/04/09 06:00
PHST- 2019/09/23 00:00 [received]
PHST- 2020/03/02 00:00 [accepted]
PHST- 2020/04/09 06:00 [entrez]
PHST- 2020/04/09 06:00 [pubmed]
PHST- 2020/04/09 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2020.00172 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2020 Mar 19;8:172. doi: 10.3389/fcell.2020.00172. 
      eCollection 2020.