Diabetes type animal models

Knockout mice have been reported for several FATPs [1]. As insulin desensitization has been closely linked to excessive fatty acid uptake and intracellular diacylgly-cerol and TG accumulation, these animal models were particularly evaluated in the context of protection from diet-induced type 2 diabetes ( Type 2 Diabetes Mellitus (T2DM)). In addition, studies on human subjects have also established genetic links between polymorphisms in FATP genes and metabolic alterations [1]. 

The nonobese diabetic mouse (NOD), as well as the biobreeding (BB) rats are the two rodent models whose diabetes-related immunopathology is considered to be quite similar to that in humans. Studies in these animal models have revealed that autoreactive T cells that mediate islet 8 cell destruction belong to the Thl subset of T cells (produce IL-2 and IFN-7), whereas regulatory T cells are of the Th2 type (produce IL-4 and IL-10). Because Thl and Th2 cells are mutually inhibitory, there have been many trials using IL-4 and/or IL-10 for the prevention of autoimmune disease, like autoimmune diabetes, rheumatoid arthritis (Evans et al., 1996 Boyle et al., 1999), and inflammatory bowel disease (Rogy et al., 2000). 

Circulating glucose and insulin levels are the key values for a diagnosis of type II diabetes. Obesity and elevated levels of non-esterified fatty acids (NEFA) are known to cause insulin resistance and diabetes. Comorbidity of T2DM and dyslipidemia are common in animal models and in clinical populations and therefore, cholesterol, triglycerides, inflammation markers, and blood pressure are often measured within the same experiments. However, for the purpose of this chapter, we will cover only values directly linked to T2DM. 

Autoimmune mechanisms are blamed for the destruction of pancreatic p cells in overt type 1 diabetes. The exact means, however, by which this selective destruction occurs in humans is unknown (Atkinson and Maclaren, 1994). In order to gain an insight into the human disease, various animal models have been developed and extensively studied the often investigated one being the non-obese diabetic (NOD) mouse (Atkinson and Leiter, 1999). 

Vanadium compounds have also been shown to be effective in animal models of insulin resistance and type 2 diabetes. Oral administration of vanadium compounds lowered blood glucose levels to near normal in the ob/ob and db/db mouse and fa/fa rat [149-151], These rodent models are homozygous for the indicated gene and are characterized by obesity, hyperglycemia, and hyperinsulinemia [12]. The ob allele is the gene for leptin, whereas db and fa are the genes for the leptin receptor in the mouse and rat, respectively. Leptin is one of the cytokine hormones that are produced in fat cells and act on receptors in the central nervous system. Its effects involve inhibition of food intake and promotion of energy expenditure [99],... 

Treatment with either vanadium salts or organic complexes of vanadium have decreased plasma insulin levels and improved insulin sensitivity in animal models of both insulin resistance and type 2 diabetes. This work has recently been reviewed [13]. The Zucker Diabetic Fatty (ZDF) rat develops overt hyperglycemia in the presence of hyperinsulinemia followed by [3-cell depletion. This is a type 2 diabetic rat model developed from the Zucker Fatty (fa/fa) rat. In these animals, chronic treatment with vanadium reduced the elevated plasma glucose levels [152,153], The effect in the type 2 models of diabetes can take weeks to develop, whereas the effect in the type 1 models of diabetes are seen within 3 to 4 days. 

A wide spectrum of thiazolidinedione compounds have been synthesized and characterized over the past 15 years. In general, these compounds were shown to be active in obese rodent models of type 2 diabetes but were not active in insulin-deficient diabetes, as in streptozo-tocin-treated rats. Thus, the compounds were shown to be insulin sensitizers with little or no potential to evoke hypoglycemia. In addition to potent insulin-sensitizing and glucose-lowering effects, the thiazolidinediones also showed substantial efficacy with respect to hypertriglyceridemia in animal models. A small number of thiazolidinediones have... 

Ingestion of fenugreek powder reduces total cholesterol and triglyceride levels. Fenugreek is thus considered a dietary supplement for hyperlipidaemia and atherosclerosis in diabetic subjects (Sharma et al., 1996a). The antidiabetic effects of fenugreek seeds in type I and type II diabetes in both human and animal models have been well established (Basch et al, 2003). 

Hannan, J.M., Ali, L., Rokeya, B., Khaleque, J., Akhter, M., Flatt, P.R. and Abdel-Wahab, Y.H. (2007) Soluble dietary fibre fraction of Trigonella foenum-graecum (fenugreek) seed improves glucose homeostasis in animal models of type 1 and type 2 diabetes by delaying carbohydrate digestion and absorption, and enhancing insulin action. British Journal of Nutrition 97(3), 51 4-521. 

Diabetes mellitus (DM) is an increasingly common disease of sugar metabolism. Juvenile-onset diabetes, also known as Type I or insulin-dependent diabetes (IDDM), is an autoimmune disease that results in decreased release of insulin by the pancreas. Late-onset diabetes, also known as Type II or non-insulin-dependent diabetes (NIDDM), results from reduced sensitivity of cells to the insulin signal. A convenient animal model for studying diabetes and testing alternative therapies is the streptozotocin-freated diabetic rat. Streptozotocin (STZ) attacks the pancreas and decreases insulin production and release, thus, mimicking many aspects of the human disease. Since insulin is not orally absorbed, the oral administration of vanadium compounds that are insuhn-mimetic or insulin-enhancing would be a very attractive therapy ... 

Studies using experimental diabetic animal models have indicated that xenobiotic-induced hepatotoxicity is modulated in diabetes. Hepatotoxicity of several structurally and mechanistically diverse chemicals, such as chloroform, thioacetamide, menadione, nitro-soamines, bromobenzene, and CCI4, is significantly increased in type 1 diabetic rats. It was reported that thioacetamide-induced hepatotoxicity was potentiated in alloxan- or streptozotocin-diabetic rats. Recent studies have confirmed the potentiation of thioacetamide hepatotoxicity in streptozotocin-diabetic rats. Several studies have shown that hepatotoxicity of CCI4 is potentiated in alloxan- or streptozotocin-induced type 1 diabetic rats. 

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