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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of the present study was to develop a rat model that replicates the natural history and metabolic characteristics of human type 2 diabetes and is also suitable for pharmacological screening. Male Sprague-Dawley rats (160-180 g) were divided into two groups and fed with commercially available normal pellet diet (NPD) (12% calories as fat) or in-house prepared high-fat diet (HFD) (58% calories as fat), respectively, for a period of 2 weeks. The HFD-fed rats exhibited significant increase in body weight, basal plasma glucose (PGL), insulin (PI), triglycerides (PTG) and total cholesterol (PTC) levels as compared to NPD-fed control rats. Besides, the HFD rats showed significant reduction in glucose disappearance rate (K-value) on intravenous insulin glucose tolerance test (IVIGTT). Hyperinsulinemia together with reduced glucose disappearance rate (K-value) suggested that the feeding of HFD-induced insulin resistance in rats. After 2 weeks of dietary manipulation, a subset of the rats from both groups was injected intraperitoneally with low dose of streptozotocin (STZ) (35 mg kg(-1)). Insulin-resistant HFD-fed rats developed frank hyperglycemia upon STZ injection that, however, caused only mild elevation in PGL in NPD-fed rats. Though there was significant reduction in PI level after STZ injection in HFD rats, the reduction observed was only to a level that was comparable with NPD-fed control rats. In addition, the levels of PTG and PTC were further accentuated after STZ treatment in HFD-fed rats. In contrast, STZ (35 mg kg(-1), i.p.) failed to significantly alter PI, PTG and PTC levels in NPD-fed rats. Thus, these fat-fed/STZ-treated rats simulate natural disease progression and metabolic characteristics typical of individuals at increased risk of developing type 2 diabetes because of insulin resistance and obesity. Further, the fat-fed/STZ-treated rats were found to be sensitive for glucose lowering effects of insulin sensitizing (pioglitazone) as well as insulinotropic (glipizide) agents. Besides, the effect of pioglitazone and glipizide on the plasma lipid parameters (PTG and PTC) was shown in these diabetic rats. The present study represents that the combination of HFD-fed and low-dose STZ-treated rat serves as an alternative animal model for type 2 diabetes simulating the human syndrome that is also suitable for testing anti-diabetic agents for the treatment of type 2 diabetes.
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PMID:Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. 1597 93

Metformin, an anti-diabetic drug used in type 2 diabetes treatment, is reported to have oncopreventive or therapeutic roles in several human cancers. The present study investigated the therapeutic potential of physiologic dose of metformin in PTC. Metformin inhibited PTC cell viability and increased cell apoptosis in various doses (0.5-20mM) in BCPAP and BHP10-3SC cells. Western blot analysis demonstrated that the p-AMPK/AMPK ratio increased with increased metformin treatment. The ectopic tumor experiment was performed using BHP10-3SC cells and athymic nude mice. Oral metformin treatment via drinking water significantly delayed tumor growth in both tumor development model and established tumor models. Necrotic area in tumors significantly increased with metformin treatment. Western blot analysis revealed an increase in p-AMPK/AMPK ratio and suppressions of mTOR and Akt expressions in metformin-treated mice compared to the results in mock-treated control mice. Our results indicate that a physiologic dose of metformin has anti-tumorigenic effects that result from activation of AMPK signaling and inhibition of Akt signaling.
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PMID:Therapeutic potential of metformin in papillary thyroid cancer in vitro and in vivo. 2490 37

In the past few decades, the incidence of thyroid cancer (TC), namely of its papillary hystotype (PTC), has shown a steady increase worldwide, which has been attributed at least in part to the increasing diagnosis of early stage tumors. However, some evidence suggests that environmental and lifestyle factors can also play a role. Among the potential risk factors involved in the changing epidemiology of TC, particular attention has been drawn to insulin-resistance and related metabolic disorders, such as obesity, type 2 diabetes, and metabolic syndrome, which have been also rapidly increasing worldwide due to widespread dietary and lifestyle changes. In accordance with this possibility, various epidemiological studies have indeed gathered substantial evidence that insulin resistance-related metabolic disorders might be associated with an increased TC risk either through hyperinsulinemia or by affecting other TC risk factors including iodine deficiency, elevated thyroid stimulating hormone, estrogen-dependent signaling, chronic autoimmune thyroiditis, and others. This review summarizes the current literature evaluating the relationship between metabolic disorders characterized by insulin resistance and the risk for TC as well as the possible underlying mechanisms. The potential implications of such association in TC prevention and therapy are discussed.
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PMID:Insulin Resistance: Any Role in the Changing Epidemiology of Thyroid Cancer? 2918 36