Animal models in type 2 diabetes research: An overview K

Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research, Mohali, India.
The Indian Journal of Medical Research (Impact Factor: 1.66). 04/2007; 125(3):451-72.
Source: PubMed

ABSTRACT Type 2 diabetes is a complex and heterogeneous disorder presently affecting more than 100 million people worldwide and causing serious socio-economic problems. Appropriate experimental models are essential tools for understanding the pathogenesis, complications, and genetic or environmental influences that increase the risks of type 2 diabetes and testing of various therapeutic agents. The animal models of type 2 diabetes can be obtained either spontaneously or induced by chemicals or dietary or surgical manipulations and/or by combination thereof. In recent years, large number of new genetically modified animal models including transgenic, generalized knock-out and tissue-specific knockout mice have been engineered for the study of diabetes. This review gives an overview on the animal models of type 2 diabetes with reference to their origin/source, characteristic features, underlying causes/mechanism(s), advantages and disadvantages to the investigators in diabetes research. In addition, it especially describes the appropriate selection and usefulness of different animal models in preclinical testing of various new chemical entities (NCEs) for the treatment of type 2 diabetes.

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Available from: Ramarao Poduri, Jul 28, 2015
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    • ") contains a recessive mutation that leads to a leptin receptor deficiency and homozygous animals (fa/fa) present obesity, insulin resistance and hyperinsulinemia in the presence of hypertension. In this model, all fatty males become hyperglycemic by 8 weeks of age and glucose remains elevated throughout their lifespan (Srinivasan and Ramarao 2007). Tissue renin-angiotensin system (RAS) overactivity is a hallmark of diabetes and contributes to target organ damage (reviewed in Ribeiro-Oliveira et al. 2008). "
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    ABSTRACT: Hearing loss secondary to diabetes remains under debate. In our study, we used Zucker Diabetic Fatty (ZDF) rats as an animal model of type 2 diabetes to investigate whether (1) hearing ability impairment and structural alterations of the inner ear occur in diabetes and (2) an angiotensin II receptor blocker (losartan) can protect rats from diabetic damage. Homozygous mutants were treated with a placebo or losartan and heterozygous animals served as non-diabetic controls. All animals underwent immunohistochemical and electronmicroscopical analysis. Functional testing of hearing ability was performed by click-evoked auditory brainstem responses. The present study showed significant sensorineural hearing impairment in placebo-treated diabetic rats (hearing threshold, 45.0 ± 2.1 dB SPL) compared to both non-diabetic controls (34.7 ± 4 dB SPL) and losartan-treated diabetic rats (36.1 ± 7.4 dB SPL). Concurrently, the functional decline in the placebo-treated rats was associated with significant morphological abnormalities, particularly in the intermediate cells of the stria vascularis and with strial dysfunction. These degenerative changes were indicated by the down-regulation of several pumps, ionic and cellular channels, which are involved in the cycling of K(+) and the maintenance of the endocochlear potential essential for the hearing process. Thus, the inner ear can be regarded as a target organ during hyperglycemic disorders and a metabolically induced "diabetic otopathy" may be added to angiopathy, nephropathy and neuropathy as a specific complication of diabetes mellitus. Blockade of the angiotensin II receptor can prevent this "diabetic otopathy" despite hyperglycemic serum levels.
    Cell and Tissue Research 06/2015; DOI:10.1007/s00441-015-2215-7 · 3.33 Impact Factor
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    • "A single intraperitoneal injection of streptozotocin (STZ) at a dose of 100 mg/kg was employed to induce DM1 (Srinivasan and Ramarao, 2007; Hayashi et al., 2006). STZ was freshly prepared in 0.05 M sodium citrate, pH 4.5. "
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    ABSTRACT: Diabetes mellitus (DM) type 1 is a chronic disease characterized by hyperglycemia and lacking of insulin. Oxidative stress participates in development and progression of DM, in which changes of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) content were noted in DM mice. In this study, the effects of GSH supplement on anti-oxidation system in streptozotocin-induced DM type 1 Imprinting Control Region (ICR) mice were determined. The co-treatment of insulin and GSH significantly lowered the hepatic manganese superoxide dismutase (Mn-SOD), CAT, and GPx mRNA expression. Moreover, co-administration of insulin and GSH restored SOD and CAT activities to non-DM group except that of the CAT activity in the kidney. The GSH contents and GSH/GSSG ratio in the mouse livers were normalized to the normal levels by the GSH treatment and the co-administration of insulin and GSH. These observations reveal that GSH supplement potentially has the protective roles in delaying diabetic progression via the improvement of antioxidant balance.
    Pakistan journal of pharmaceutical sciences 11/2014; 27(6):1731-1737. · 0.95 Impact Factor
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    • "Diabetes mellitus is one of the most prevalent diseases in endocrine gland system with an increasing incidence in human community [1] . Type I diabetes is caused by insulin secretion deficit while type II diabetes is accompanied with progressive rate of insulin resistance in liver and peripheral tissues, reducing β-cells mass, and deficient insulin secretion [2] [3] . This disease brings about acute metabolic side effects including ketoacidosis, hyperosmolar coma accompanied with chronic disorders and long term, adverse side effects such as retinopathy, renal failure, neuropathy, skin complications, as well as increasing cardiovascular complication risks [4] [5] . "
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    ABSTRACT: Objective: To collect and document information on anti-diabetic plants traditionally used in the treating of diabetes in Urmia at Northwest Iran because ethnomedicines are considered as valuable sources to find new potential drugs. Methods: We used the method of direct observation and interview (35 traditional healers) along with gathering herbarium specimens mentioned plants in site. Results: There were 30 medicinal plants from 17 families for the treatment of diabetes. The family with most plants was Lamiaceae (20%). Leaves (20%) are often used and its form is decoction (70%). It was also found that Citrullus colocynthis has the most frequency of use among traditional healers. Conclusions: Furthermore, base on current findings many of the mentioned plants have potential active ingredients to influence diabetes.
    Asian Pacific Journal of Tropical Medicine 10/2014; 7:348-354. DOI:10.1016/S1995-7645(14)60257-1 · 0.93 Impact Factor
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