Cellular stress, excessive apoptosis, and the effect of metformin in a mouse model of type 2 diabetic embryopathy

Yanqing Wu, Wang Fang, Mao Fu, Wang Cheng, Michael J. Quon, Peixin Yang

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2526-2536
Number of pages11
JournalDiabetes
Volume64
Issue number7
DOIs
StatePublished - Jul 1 2015

Fingerprint

Fetal Diseases
Metformin
High Fat Diet
Diabetes Mellitus
Embryonic Structures
Apoptosis
Type 2 Diabetes Mellitus
Fats
Neuroepithelial Cells
Diet
Control Groups
Endoplasmic Reticulum Stress
Glucose Intolerance
Neural Tube Defects
Caspases
Nonesterified Fatty Acids
Drinking Water
Hyperglycemia
Insulin Resistance
Rodentia

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Cellular stress, excessive apoptosis, and the effect of metformin in a mouse model of type 2 diabetic embryopathy. / Wu, Yanqing; Fang, Wang; Fu, Mao; Cheng, Wang; Quon, Michael J.; Yang, Peixin.

In: Diabetes, Vol. 64, No. 7, 01.07.2015, p. 2526-2536.

Research output: Contribution to journalArticle

Wu, Yanqing ; Fang, Wang ; Fu, Mao ; Cheng, Wang ; Quon, Michael J. ; Yang, Peixin. / Cellular stress, excessive apoptosis, and the effect of metformin in a mouse model of type 2 diabetic embryopathy. In: Diabetes. 2015 ; Vol. 64, No. 7. pp. 2526-2536.
@article{b4d3d33f194a49ac9f55b0535ac754f2,
title = "Cellular stress, excessive apoptosis, and the effect of metformin in a mouse model of type 2 diabetic embryopathy",
abstract = "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.",
author = "Yanqing Wu and Wang Fang and Mao Fu and Wang Cheng and Quon, {Michael J.} and Peixin Yang",
year = "2015",
month = "7",
day = "1",
doi = "10.2337/db14-1683",
language = "English (US)",
volume = "64",
pages = "2526--2536",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "7",

}

TY - JOUR

T1 - Cellular stress, excessive apoptosis, and the effect of metformin in a mouse model of type 2 diabetic embryopathy

AU - Wu, Yanqing

AU - Fang, Wang

AU - Fu, Mao

AU - Cheng, Wang

AU - Quon, Michael J.

AU - Yang, Peixin

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84940874434&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940874434&partnerID=8YFLogxK

U2 - 10.2337/db14-1683

DO - 10.2337/db14-1683

M3 - Article

VL - 64

SP - 2526

EP - 2536

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 7

ER -