Modelling gestational diabetes mellitus: large animals hold great promise
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Modelling gestational diabetes mellitus: large animals hold great promise Xiang Gao 1,2 & Junsheng He 1,2 & Anming Zhu 1,2 & Kang Xie 1,2 & Kaixuan Yan 1,2 & Xue Jiang 1,2 & Ying Xu 3 & Qin Li 4 & Aimin Xu 5 & Dewei Ye 1,2 & Jiao Guo 1,2 Accepted: 18 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Gestational diabetes mellitus (GDM) characterized by hyperglycemia during pregnancy is a risk factor for various maternal and fetal complications. The key pathophysiological mechanisms underlying its development have not been elucidated, largely due to the lack of a model that accurately simulates the major clinical and pathological features of human GDM. In this review, we discuss the refined criteria for an ideal animal model of GDM, focusing on the key clinical and pathophysiological characteristics of human GDM. We provide a comprehensive overview of different models and currently used species for GDM research. In general, insulin insufficiency consequent to pancreatic β-cell death represents the current leading strategy to mimic human GDM-like hyperglycemia in animals. Nonetheless, these models have a limited capacity to mimic the natural history of GDM, the marked alteration in circulating estrogen/ progestogen, obesity and its related metabolic complications. We discuss emerging evidence of the increased susceptibility to GDM in rodents and large animals with genetic modifications in pregnancyrelated hormones. An appraisal of current GDM models suggests that a combination strategy involving dietary stress, pregnancyrelated hormones, insulin resistance and metabolic disorders might enable the development of better GDM models and expedite the translation of basic research findings to GDM treatment. Keywords Hyperglycemia . Glucose metabolism . Animal model . Insulin resistance . Pregnancy complication
Abbreviations ALX alloxan BMI body mass index Foxd3 forkhead box D3 FoxM1 forkhead box M1 GDM gestational diabetes mellitus GLUT4 glucose transporter 4 GSIS glucose-stimulated insulin secretion test
HFD HFHS IR PGH PL PNDM PRL Prlr
high-fat diet high-fat and high-sucrose insulin resistance placental growth hormone placental lactogen permanent neonatal diabetes mellitus prolactin prolactin receptors
Xiang Gao, Junsheng He and Anming Zhu contributed equally to this work. * Dewei Ye [email protected]
2
Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Room 403, 4th Floor, Science and Technology Building, 280 Waihuan East Road, Guangzhou Higher Education Mega, Guangzhou, China
3
The First Affiliated Hospital/School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, China
4
Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
5
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China
* Jiao Guo [email protected] 1
Key Laboratory of Glucolipid Metabo
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