Rodent models of diabetic cardiomyopathy

Abstract

Diabetic cardiomyopathy increases the risk of heart failure in individuals with diabetes, independently of co-existing coronary artery disease and hypertension. The underlying mechanisms for this cardiac complication are incompletely understood. Research on rodent models of type 1 and type 2 diabetes, and the use of genetic engineering techniques in mice, have greatly advanced our understanding of the molecular mechanisms responsible for human diabetic cardiomyopathy. The adaptation of experimental techniques for the investigation of cardiac physiology in mice now allows comprehensive characterization of these models. The focus of the present review will be to discuss selected rodent models that have proven to be useful in studying the underlying mechanisms of human diabetic cardiomyopathy, and to provide an overview of the characteristics of these models for the growing number of investigators who seek to understand the pathology of diabetes-related heart disease.

β3 Adrenergic Stimulation Restores Nitric Oxide/Redox Balance and Enhances Endothelial Function in Hyperglycemia

“…We set out to determine the redox effects of β 3 AR stimulation in experimental hyperglycemia and it was important to first examine whether diabetes‐inducing agents have confounding effects on the target proteins of interest. The most commonly used diabetogenic agent STZ, a glucosamine‐nitrosourea taken up by pancreatic β cells causing their necrosis,30 decreased the oxidative modification of β 1 Na + ‐K + pump subunit in vitro. With short in vitro exposure time, this is likely due to the property of STZ to release NO,31 shown to reduce β 1 subunit glutathionylation 11.…”

“…With short in vitro exposure time, this is likely due to the property of STZ to release NO,31 shown to reduce β 1 subunit glutathionylation 11. When administered at high toxic doses in vivo, STZ increases cellular ROS levels and causes undesirable extrapancreatic genotoxic effects that further complicate differentiation of STZ direct molecular effects from effects of diabetes that it induces 30. Alloxan, the second most commonly used diabetogenic agent, increased β 1 pump subunit glutathionylation both in vitro and in vivo independently of diabetogenesis.…”

“…We detected no effect on metabolic variables except serum glucose for the duration of S961 infusion and, importantly, no effects on nutritional status or ketoacidosis, a complication often seen in alloxan‐ and STZ‐induced diabetes. Ketoacidosis increases ROS generation independently of hyperglycemia 30. Of mechanistic importance, S961 provides a model of hyperglycemia and insulin signaling blockade, central features in pathobiology of vascular disease in diabetes16, 17 as opposed to the commonly used insulinopenic hyperglycemia models where insulin signaling is usually unaltered.…”

Characterization of Peripheral Neuropathy in Rat Model of Type 2 Diabetes

“…No animal model is perfect, and current rodent models of type 2 diabetes have been shown to have some limitations (reviewed by Bugger and Abel). 4 Most of these models comprise of transgenic animals which are expensive to maintain and also fail to mimic the multifactorial disease pathogenesis process. 5 A rat model first proposed by Reed et al, 6 and later modified by Srinivasan et al, 7 aimed to induce type 2 diabetes using high-fat diet (HFD) resulting in peripheral insulin resistance, followed by a low dose of the pancreatic β-cell toxin, streptozotocin (STZ).…”

Hydrogen sulfide exhibits cardioprotective effects by decreasing endoplasmic reticulum stress in a diabetic cardiomyopathy rat model

“…Investigation revealed that patients with diabetes mellitus (DM) were more likely to suffer from coronary artery disease, hypertension and mortality following myocardial infarction (7,8), while DC was one of the most common serious cardiovascular complications of DM (9). Cellular metabolic abnormalities and defections of organelles were shown to participate in the pathology of DC (10)(11)(12)(13)(14), which is a chronic and complex process associated with impaired calcium homeostasis, increased lipid uptake, myocardial insulin resistance, glucotoxicity, increased oxidative stress and activation of the renin-angiotensin system (15). Furthermore, the pathological role of endoplasmic reticulum (ER) stress in DC has been noted in a number of studies (16)(17)(18).…”