Experimental models of type-2 diabetes

Research Works

The main objective of this topic is to present two complementary male and female animal models used by the team, representing different stages of the disease’s evolution, from the prediabetes (HFS rat) stage to the establishment of proven type 2 diabetes (Goto-Kakizaki rat). These models are very relevant to study sexual dimorphism in cardiovascular complications associated with prediabetes and type 2 diabetes, a novel and currently under-researched topic.

-High Fat High Sucrose (HFS) rat: This model induced a prediabetic rat in female Wistar rats and early cardiac changes from the three months of diet characterized by increased left ventricular systolic and diastolic wall thickness and myocardial perfusion (see Figure below) (Fourny et al. 2019). Interestingly, sex differences are present in male and female Wistar rats submitted to HFS diet, regarding tolerance to glucose, body weight and heart weight-to-tibia length ratio (Fourny et al. 2021). Since 2019, this animal model has been largely used in the team for developing some specific therapeutic approaches (Jouenne et al. 2021). Recently, we reported for the first time a strong correlation between cardiac alterations and hepatic steatosis state in female prediabetic rats submitted to 5 months of HFS diet (Jouenne et al. 2022).

-Goto-Kakizaki (GK) rat: The GK rat is a well-known polygenic non obese animal model of type 2 diabetes extensively studied in the team these last years (Desrois et al. 2010, 2017]. Specific sex differences at basal state are present in GK rat hearts with an endothelial damage and altered “over-regulation” of the NO pathway in females compared with male GK (Desrois et al. 2017).  In 2019, we reported cardioprotective effect of resveratrol, a powerful antioxidant, against ischemia-reperfusion injury in type 2 diabetic female rats via increased high energy compound contents and expression of protein involved in NO pathway (Fourny et al. 2019) (see Figure below). Recently, other specific sex differences in GK rats submitted to myocardial ischemia-reperfusion injury has been described with greater impairment of energy metabolism and coronary flow in female than in male GK rats (Fourny et al. 2020).

Research collaboration contracts with the Boehringer-Ingelheim Laboratory (Pharma GmbH&Co): 2018-2020.

Fourny et al. 2019: In vivo MRI experiments on whole animal

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Fourny et al. 2019: Ex vivo myocardial function and energy metabolism assessed by P-31 MRS on isolated perfused rat heart