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Cellular Stress, Excessive Apoptosis, and the Effect of Metformin in a Mouse Model of Type 2 Diabetic Embryopathy

Increasing prevalence of type 2 diabetes in women of childbearing age has led to a higher incidence of diabetes-associated birth defects. We established a model of type 2 diabetic embryopathy by feeding 4-week-old female mice a high-fat diet (HFD) (60% fat). After 15 weeks on HFD, the mice showed ch...

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Autores principales: Wu, Yanqing, Wang, Fang, Fu, Mao, Wang, Cheng, Quon, Michael J., Yang, Peixin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477360/
https://www.ncbi.nlm.nih.gov/pubmed/25720389
http://dx.doi.org/10.2337/db14-1683
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author Wu, Yanqing
Wang, Fang
Fu, Mao
Wang, Cheng
Quon, Michael J.
Yang, Peixin
author_facet Wu, Yanqing
Wang, Fang
Fu, Mao
Wang, Cheng
Quon, Michael J.
Yang, Peixin
author_sort Wu, Yanqing
collection PubMed
description Increasing prevalence of type 2 diabetes in women of childbearing age has led to a higher incidence of diabetes-associated birth defects. We established a model of type 2 diabetic embryopathy by feeding 4-week-old female mice a high-fat diet (HFD) (60% fat). After 15 weeks on HFD, the mice showed characteristics of type 2 diabetes mellitus (DM) and were mated with lean male mice. During pregnancy, control dams fed a normal diet (10% fat) were maintained on either normal diet or HFD, serving as a control group with elevated circulating free fatty acids. DM dams produced offspring at a rate of 11.3% for neural tube defect (NTD) formation, whereas no embryos in the control groups developed NTDs. Elevated markers of oxidative stress, endoplasmic reticulum stress, caspase activation, and neuroepithelial cell apoptosis (causal events in type 1 diabetic embryopathy) were observed in embryos of DM dams. DM dams treated with 200 mg/kg metformin in drinking water ameliorated fasting hyperglycemia, glucose intolerance, and insulin resistance with consequent reduction of cellular stress, apoptosis, and NTDs in their embryos. We conclude that cellular stress and apoptosis occur and that metformin effectively reduces type 2 diabetic embryopathy in a useful rodent model.
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spelling pubmed-44773602016-07-01 Cellular Stress, Excessive Apoptosis, and the Effect of Metformin in a Mouse Model of Type 2 Diabetic Embryopathy Wu, Yanqing Wang, Fang Fu, Mao Wang, Cheng Quon, Michael J. Yang, Peixin Diabetes Pathophysiology Increasing prevalence of type 2 diabetes in women of childbearing age has led to a higher incidence of diabetes-associated birth defects. We established a model of type 2 diabetic embryopathy by feeding 4-week-old female mice a high-fat diet (HFD) (60% fat). After 15 weeks on HFD, the mice showed characteristics of type 2 diabetes mellitus (DM) and were mated with lean male mice. During pregnancy, control dams fed a normal diet (10% fat) were maintained on either normal diet or HFD, serving as a control group with elevated circulating free fatty acids. DM dams produced offspring at a rate of 11.3% for neural tube defect (NTD) formation, whereas no embryos in the control groups developed NTDs. Elevated markers of oxidative stress, endoplasmic reticulum stress, caspase activation, and neuroepithelial cell apoptosis (causal events in type 1 diabetic embryopathy) were observed in embryos of DM dams. DM dams treated with 200 mg/kg metformin in drinking water ameliorated fasting hyperglycemia, glucose intolerance, and insulin resistance with consequent reduction of cellular stress, apoptosis, and NTDs in their embryos. We conclude that cellular stress and apoptosis occur and that metformin effectively reduces type 2 diabetic embryopathy in a useful rodent model. American Diabetes Association 2015-07 2015-02-26 /pmc/articles/PMC4477360/ /pubmed/25720389 http://dx.doi.org/10.2337/db14-1683 Text en © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
spellingShingle Pathophysiology
Wu, Yanqing
Wang, Fang
Fu, Mao
Wang, Cheng
Quon, Michael J.
Yang, Peixin
Cellular Stress, Excessive Apoptosis, and the Effect of Metformin in a Mouse Model of Type 2 Diabetic Embryopathy
title Cellular Stress, Excessive Apoptosis, and the Effect of Metformin in a Mouse Model of Type 2 Diabetic Embryopathy
title_full Cellular Stress, Excessive Apoptosis, and the Effect of Metformin in a Mouse Model of Type 2 Diabetic Embryopathy
title_fullStr Cellular Stress, Excessive Apoptosis, and the Effect of Metformin in a Mouse Model of Type 2 Diabetic Embryopathy
title_full_unstemmed Cellular Stress, Excessive Apoptosis, and the Effect of Metformin in a Mouse Model of Type 2 Diabetic Embryopathy
title_short Cellular Stress, Excessive Apoptosis, and the Effect of Metformin in a Mouse Model of Type 2 Diabetic Embryopathy
title_sort cellular stress, excessive apoptosis, and the effect of metformin in a mouse model of type 2 diabetic embryopathy
topic Pathophysiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477360/
https://www.ncbi.nlm.nih.gov/pubmed/25720389
http://dx.doi.org/10.2337/db14-1683
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