Rodent models for diabetes

Abstract

Diabetes mellitus (DM) is associated with many health complications and is potentially a morbid condition. As prevalence increases at an alarming rate around the world, research into new antidiabetic compounds with different mechanisms is the top priority. Therefore, the preclinical experimental induction of DM is imperative for advancing knowledge, understanding pathogenesis, and developing new drugs. Efforts have been made to examine recent literature on the various induction methods of Type I and Type II DM. The review summarizes the different in vivo models of DM induced by chemical, surgical, and genetic (immunological) manipulations and the use of pathogens such as viruses. For good preclinical assessment, the animal model must exhibit face, predictive, and construct validity. Among all reported models, chemically induced DM with streptozotocin was found to be the most preferred model. However, the purpose of the research and the outcomes to be achieved should be taken into account. This review was aimed at bringing together models, benefits, limitations, species, and strains. It will help the researcher to understand the pathophysiology of DM and to choose appropriate animal models.

Keywords: Diabetes mellitus; Hyperglycemia; Insulin resistance; Streptozotocin.

Fig. 1

Animal models for Type 1 and Type 2 diabetes mellitus. Streptozotocin (STZ), nicotinamide (NA), non-obese diabetic (NOD), Bio-breeding rat (BB), Kilham rat virus (KRV), high-fat diet (HFD), Goto-Kakizaki (GK), New Zealand obese (NZO) mouse, Zucker Diabetic Sprague–Dawley rat (ZDSD), Gold thioglucose (GTG)

Fig. 2

Chemicals inducing Type 2 diabetes mellitus and their mechanism of action. (i) NA + STZ model where STZ enters the β cell and damages DNA and increases the activity of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP-1). Excess activity of enzyme results in depletion of intracellular NAD (+) and ATP, and the insulin-secreting cells undergo necrosis. NA shows partial protection due to the inhibition of PARP-1, preventing depletion of NAD (+) and ATP in the cells exposed to STZ activity. (ii) HFD + STZ model-Animals introduced to obesogenic diet, which leads to development of obesity, followed by introduction of STZ, leading to hyperglycemia, IR, hyperinsulinemia, and inflammation. (iii) Fructose + STZ-It leads to increased BG, IR, free fatty acids, oxidative stress, and leptin resistance. (iv) GTG-induced T2DM results in development of obesity, increased BG, and impaired insulin secretion. Streptozotocin (STZ), Nicotinamide (NA), deoxyribonucleic acid (DNA), poly(ADP-ribose) polymerases (PARPs), nicotinamide adenine dinucleotide (NAD), high-fat diet (HFD), insulin resistance (IR), gold thioglucose (GTG), blood glucose (BG)