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Therapeutic approaches to target inflammation in type 2 diabetes.

ABSTRACT: BACKGROUND:Chronic inflammation may participate in the pathogenesis of insulin resistance, type 2 diabetes, and cardiovascular disease and may be a common denominator that links obesity to these disease states. CONTENT:Epidemiologic studies have linked inflammatory biomarkers to incident diabetes and cardiovascular disease risk. Cellular and animal studies have provided support to the idea that inflammation mediates these disease processes, providing impetus to pharmacologically target these pathways for disease treatment and prevention. We review clinical strategies to target inflammation, with a focus on the antiinflammatory and antihyperglycemic effects of salicylates. SUMMARY:The evolving concept of diet-induced obesity driving insulin resistance, type 2 diabetes, and cardiovascular disease through immunologic processes provides new opportunities for the use of antiinflammatory strategies to correct the metabolic consequences of excess adiposity.

SUBMITTER: Goldfine AB

PROVIDER: S-EPMC3227024 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Therapeutic approaches to target inflammation in type 2 diabetes.

Goldfine Allison B AB Fonseca Vivian V Shoelson Steven E SE

Clinical chemistry 20101122 2

<h4>Background</h4>Chronic inflammation may participate in the pathogenesis of insulin resistance, type 2 diabetes, and cardiovascular disease and may be a common denominator that links obesity to these disease states.<h4>Content</h4>Epidemiologic studies have linked inflammatory biomarkers to incident diabetes and cardiovascular disease risk. Cellular and animal studies have provided support to the idea that inflammation mediates these disease processes, providing impetus to pharmacologically t ...[more]

PMID: 21098138

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Project description:BackgroundThyroid cancer, as with other types of cancer, is dependent on angiogenesis for its continued growth and development. Interestingly, estrogen has been shown to contribute to thyroid cancer aggressiveness in vitro, which is in full support of the observed increased incidence of thyroid cancer in women over men. Provided that estrogen has been observed to contribute to increased angiogenesis of estrogen responsive breast cancer, it is conceivable to speculate that estrogen also contributes to angiogenesis of estrogen responsive thyroid cancer.MethodsIn this study, three human thyroid cancer cells (B-CPAP, CGTH-W-1, ML-1) were treated with estrogen alone or estrogen and anti-estrogens (fulvestrant and 3,3'-diindolylmethane, a natural dietary compound) for 24 hours. The cell culture media was then added to human umbilical vein endothelial cell (HUVECs) and assayed for angiogenesis associated events. Vascular endothelial growth factor (VEGF) levels were also quantified in the conditioned media so as to evaluate if it is a key player involved in these observations.ResultsConditioned medium from estrogen treated thyroid cancer cells enhanced phenotypical changes (proliferation, migration and tubulogenesis) of endothelial cells typically observed during angiogenesis. These phenotypic changes observed in HUVECs were determined to be modulated by estrogen induced secretion of VEGF by the cancer cells. Lastly, we show that VEGF secretion was inhibited by the anti-estrogens, fulvestrant and 3,3'-diindolylmethane, which resulted in diminished angiogenesis associated events in HUVECs.ConclusionOur data establishes estrogen as being a key regulator of VEGF secretion/expression in thyroid cells which enhances the process of angiogenesis in thyroid cancer. These findings also suggest the clinical utility of anti-estrogens as anti-angiogenic compounds to be used as a therapeutic means to treat thyroid cancer. We also observed that 3,3'-diindolylmethane is a promising naturally occurring anti-estrogen which can be used as a part of therapeutic regimen to treat thyroid cancer.

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Therapeutic approaches to target inflammation in type 2 diabetes.

Publications

Therapeutic approaches to target inflammation in type 2 diabetes.

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