What are the key features to look out for when inducing type 2 diabetic animal models? How will there histological and biochemical parameters be different to that of type 1 diabetic animal models? How will the type 2 animal model's lipid profile, insulin levels, post pandrial glucose levels and weight differ to that of a type 1 animal model?
I agree with Jf Thibodeau regarding body weight gain/lost when comparing type I versus type II diabetes. However, it is hard to define the main characteristics of type II diabetes in animal models since it might resemble type I, depending on the stage of the disease (for instance, if the animal has an untreated and advanced diabetes in a streptozotocin model). In my experience, a good diabetes type II model is mice fed a diet rich in simple sugars such as fructose or sucrose alone. Another good try is to combine them with saturated fat. High fat diets alone successfully increase body weight, but not always induce a huge increase in blood sugar. It is likely because you have to reduce the sugar content of the diet in order to increase fat content.
As type 1 is due to insulinemia, rodent body weight tends to decrease in comparison with healthy age-matched controls. Type 2 is generally associated with increased weight gain and dyslipidemia. If these models are used to model diabetic nephropathy, they are generally very similar in that most murine models of DN will develop early indices of renal damage, such as albuminuria, glomerular hyperfiltration, mesangial cell matrix overproduction and podocyte damage. However only a subset of models, which usually have concomitant hypertension, may develop signs of advanced DN, mimicking human disease, including tubular interstitial fibrosis and glomerular filtration decline.
The DN is an interesting question to address.
Type 2 diabetes is the late event after a phase of insulin resistance when insulin secretion is unable to correct for hyperglycemia. So I would suggest that a common feature of Type I and Type 2 diabetes is important.
I am not an expert in kidney physiopathology. Is there anay change in animals that are only insulin resistant; i.e. earlier in the pathology related to wheight gain and obesity.
Indeed, type 2 diabetic models are important to mimic the mechanisms of disease. Four important issues has to be addressed: 1.- Progression to type diabetes in the model. 2.- Irreversibility of the model. 3.- The inflammatory disease as visualized by the cytokine circulation levels and 4.- The vascular damage showing or not vascular insulin resistance.
I agree with Jf Thibodeau regarding body weight gain/lost when comparing type I versus type II diabetes. However, it is hard to define the main characteristics of type II diabetes in animal models since it might resemble type I, depending on the stage of the disease (for instance, if the animal has an untreated and advanced diabetes in a streptozotocin model). In my experience, a good diabetes type II model is mice fed a diet rich in simple sugars such as fructose or sucrose alone. Another good try is to combine them with saturated fat. High fat diets alone successfully increase body weight, but not always induce a huge increase in blood sugar. It is likely because you have to reduce the sugar content of the diet in order to increase fat content.
The renal disease in T2DM in man is a mix of hyperglycaemia induced diabetic nephropathy as seen in T1DM and macrovascular disease. Difficult to reproduce in a single model!
The best model is the ZDF rat (Zucker Diabetic Fatty) available from Charles River. Early on they show INCREASED insulin, not decreased, which is also true of early stage type 2 diabetes in humans. The rise in glucose is mainly driven by insulin resistance more than a secretory defect. Later on a secretory defect becomes more prominent. This mimics the progression of human type 2 diabetes quite well. ZDF develop renal disease, which is a consequence of increased glucose and high triglycerides.
We use both the ZDF rat and the db/db mouse. Both are leptin receptor deficient. The ZDF rat when given the correct diet will develop a disease that mimics human T2D. Interestingly, in the ZDF model, the males develop hyperglycemia on only 16% fat, while the females require much more - the recommended diet is 48% fat.
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