In Vivo Rodent Models of Type 2 Diabetes and Their Usefulness for Evaluating Flavonoid Bioactivity

Abstract

About 40% of the world’s population is overweight or obese and exist at risk of developing type 2 diabetes mellitus (T2D). Obesity is a leading pathogenic factor for developing insulin resistance (IR). It is well established that IR and a progressive decline in functional β-cell mass are hallmarks of developing T2D. In order to mitigate the global prevalence of T2D, we must carefully select the appropriate animal models to explore the cellular and molecular mechanisms of T2D, and to optimize novel therapeutics for their safe use in humans. Flavonoids, a group of polyphenols, have drawn great interest for their various health benefits, and have been identified in naturally occurring anti-diabetic compounds. Results from many clinical and animal studies demonstrate that dietary intake of flavonoids might prove helpful in preventing T2D. In this review, we discuss the currently available rodent animal models of T2D and analyze the advantages, the limitations of each T2D model, and highlight the potential anti-diabetic effects of flavonoids as well as the mechanisms of their actions.

Treatment with Mammalian Ste-20-like Kinase 1/2 (MST1/2) Inhibitor XMU-MP-1 Improves Glucose Tolerance in Streptozotocin-Induced Diabetes Mice

“…However, we believe that it is also important to study the effects of MST1 inhibition in the other type of DM, i.e., the type 2 DM. Several rodent models of T2DM are established including diet-induced T2DM (in which the animals were subjected to a high-fat and high-calorie diet for a period of time) and the genetically modified mouse models of T2DM [ 27 ].…”

The Relationship between Diabetes Mellitus Type II and Intervertebral Disc Degeneration in Diabetic Rodent Models: A Systematic and Comprehensive Review

“…Rodents could be a strong model, and the rat and mouse tail provide optimal access to IVDD, e.g., with the use of mechanical injury, asymmetrical compression, or administration of digestive enzymes. The advantages of rodent models are also the availability of numerous models of T2DM and obesity, the ease to manipulate them genetically, the short breeding span, the access to physiological and invasive testing, and the balanced cost-effectiveness [ 38 , 39 ]. In contrast, limitations include the fact that monogenic models are not representative of most human disorders [ 38 ].…”

“…The advantages of rodent models are also the availability of numerous models of T2DM and obesity, the ease to manipulate them genetically, the short breeding span, the access to physiological and invasive testing, and the balanced cost-effectiveness [ 38 , 39 ]. In contrast, limitations include the fact that monogenic models are not representative of most human disorders [ 38 ]. In addition, there are other disadvantages, such as the persistence of notochordal cells in rodents, the obvious disc size discrepancy between humans and rodents ( Figure 1 ), biomechanical differences in mechanical loading, and the ethical obstacles in the case of, e.g., creating bipedal mice [ 36 ] to mimic human conditions.…”

“…The spontaneous diabetic Torii (SDT) rat is a non-obese model of T2DM characterized by a blood glucose level of about 600 mg/dL at the age of 24 weeks and low insulin secretion caused by β-cell dysfunction. By advancing age, it exhibits decreased femoral and tibial BMD, reduced tibial three-point bending stiffness and peak load, and reduced bone formation rate [ 38 , 40 ]. The Zucker diabetic Sprague Dawley (SD) rat is a genetic-modified rat model through a leptin receptor mutation and develops rapidly a frank T2DM.…”

“…The Zucker diabetic Sprague Dawley (SD) rat is a genetic-modified rat model through a leptin receptor mutation and develops rapidly a frank T2DM. It exhibits reduced femoral length and diameter, diaphyseal cortical thickness, and cortical volumetric BMD, biomechanical changes, and reduced vertebral BMD [ 38 , 40 ]. The induction of T2DM in SD rats using alloxan has the following drawbacks: high mortality rates, ketosis, and T2DM is reversible, while the use of streptozotocin (STZ), which is used mainly for the induction of T1DM, can also induce T2DM, having the following advantages: higher selectivity to β-cells, lower mortality rate, and T2DM is irreversible [ 44 ].…”