Advancements and challenges in generating accurate animal models of gestational diabetes mellitus

Pasek, Raymond C.; Gannon, Maureen

doi:10.1152/ajpendo.00425.2013

Cited by 90Gestational Diabetes Research and ManagementPancreatic function and diabetesBirth, Development, and Health

Advancements and challenges in generating accurate animal models of gestational diabetes mellitus

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Pasek, Raymond C., Gannon, Maureen·2013·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00425.2013PMC PMC4073988

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Abstract

The maintenance of glucose homeostasis during pregnancy is critical to the health and well-being of both the mother and the developing fetus. Strikingly, approximately 7% of human pregnancies are characterized by insufficient insulin production or signaling, resulting in gestational diabetes mellitus (GDM). In addition to the acute health concerns of hyperglycemia, women diagnosed with GDM during pregnancy have an increased incidence of complications during pregnancy as well as an increased risk of developing type 2 diabetes (T2D) later in life. Furthermore, children born to mothers diagnosed with GDM have increased incidence of perinatal complications, including hypoglycemia, respiratory distress syndrome, and macrosomia, as well as an increased risk of being obese or developing T2D as adults. No single environmental or genetic factor is solely responsible for the disease; instead, a variety of risk factors, including weight, ethnicity, genetics, and family history, contribute to the likelihood of developing GDM, making the generation of animal models that fully recapitulate the disease difficult. Here, we discuss and critique the various animal models that have been generated to better understand the etiology of diabetes during pregnancy and its physiological impacts on both the mother and the fetus. Strategies utilized are diverse in nature and include the use of surgical manipulation, pharmacological treatment, nutritional manipulation, and genetic approaches in a variety of animal models. Continued development of animal models of GDM is essential for understanding the consequences of this disease as well as providing insights into potential treatments and preventative measures.

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There are limitations inherent to using animals to model human pregnancy, including differences in placental morphology, gestational length, parturition, a greater number of offspring per pregnancy, and different developmental windows of fetal and neonatal cellular differentiation and organogenesis.
“There are also limitations inherent to using animals to model human pregnancy. These include differences in placental morphology, gestational length, parturition, a greater number of offspring per pregnancy, and different developmental windows of fetal and neonatal cellular differentiation and organogenesis [88,89].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [88]
The section labeled “2010 Standards for the diagnosis of GDM” (page unavailable) says sheep share humans’ generally monotocous pregnancies, supporting the point that offspring number differs across animal models. It also gives sheep’s gestational length, but does not compare it with humans’. The passages do not establish the claimed differences in placental morphology, parturition, or fetal and neonatal developmental windows. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Insulin deficiency using streptozotocin may not accurately model the mechanisms involving gestational diabetes mellitus and its effects on the offspring cardiovascular system.
“Consequently, insulin deficiency using STZ may not accurately model the mechanisms involving GDM and its effects on the offspring cardiovascular system [88].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [88]
The discussion of chemical models (page unavailable) says STZ destroys β-cells and that STZ-based models do not truly mimic human GDM, supporting the concern about modeling GDM mechanisms. It says these models can be used to study effects on offspring development, but does not address whether they accurately model effects on the offspring cardiovascular system specifically. (LLM, conf=0.85)
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Authors: Pasek, R. C., & Gannon, M.
Affiliations: Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism,
VA Tennessee Valley Healthcare System (US)
Corresponding author: Gannon, Maureen
ORCID: Gannon, Maureen
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2013-12-01
Volume: 305
Issue: 11
Pages: E1327-E1338
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.00425.2013
PMC: PMC4073988
OpenAlex: W1970404346
Cited by: 90
References: 122
Citations by year: 2026: 7 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 9 · 2021: 8 · 2020: 14 · 2019: 8 · 2018: 6 · 2017: 7 · 2016: 7 · 2015: 4 · 2014: 3
FWCI: 0.80
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Veterans Affairs (I01 BX000990)
National Institute of Diabetes and Digestive and Kidney Diseases (5T32 DK07563, T32DK007563)
Topics: Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords: gestational diabetes mellitus, animal models, insulin signaling, type 2 diabetes risk, perinatal complications, macrosomia, fetal development, genetic models, dietary intervention, surgical manipulation, pharmacological models
MeSH terms: Adult, Animals, Diabetes Mellitus, Experimental, Female, Humans, Pancreatectomy, Pregnancy, Rodentia, Diabetes, Gestational, Animal Experimentation

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Advancements and challenges in generating accurate animal models of gestational diabetes mellitus

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