Biomedical subjects

Christine M Kusminski

Publications and source records attributed to Christine M Kusminski.

3 recordsLinked to original sources

PubMed2006

The in vitro effects of resistin on the innate immune signaling pathway in isolated human subcutaneous adipocytes.

CONTEXT: Obesity-associated inflammation is a contributory factor in the pathogenesis of type 2 diabetes mellitus (T2DM); the mechanisms underlying the progression to T2DM are unclear. The adipokine resistin has demonstrated proinflammatory properties in relation to obesity and T2DM. OBJECTIVES: The objectives of this study were to characterize resistin expression in human obesity and address the role of resistin in the innate immune pathway; to examine the influence of lipopolysaccharide, recombinant human resistin (rhResistin), insulin, and rosiglitazone in human adipocytes; and, finally, to analyze the effect of rhResistin on the expression of components of the nuclear factor-kappaB pathway and insulin signaling cascade. METHODS: Abdominal sc adipose tissue was obtained from patients undergoing elective liposuction surgery (n = 35; age, 36-49 yr; body mass index, 26.5 +/- 5.9 kg/m2). Isolated adipocytes were cultured with rhResistin (10-50 ng/ml). The level of cytokine secretion from isolated adipocytes was examined by ELISA. The effect of rhResistin on protein expression of components of the innate immune pathway was examined by Western blot. RESULTS: In vitro studies demonstrated that antigenic stimuli increase resistin secretion (P < 0.001) from isolated adipocytes. Proinflammatory cytokine levels were increased in response to rhResistin (P < 0.001); this was attenuated by rosiglitazone (P < 0.01). When examining components of the innate immune pathway, rhResistin stimulated Toll-like receptor-2 protein expression. Similarly, mediators of the insulin signaling pathway, phosphospecific c-Jun NH2-terminal kinase (JNK) 1 and JNK2, were up-regulated in response to rhResistin. CONCLUSION: Resistin may participate in more than one mechanism to influence proinflammatory cytokine release from human adipocytes, potentially via the integration of nuclear factor-kappaB and JNK signaling pathways.

Adipocytes↗

PubMed2006

Resistin.

PURPOSE OF REVIEW: Resistin, a cysteine-rich 12.5 kDa polypeptide, is a recently discovered adipocytokine with a controversial history regarding its role in the pathogenesis of obesity-mediated insulin resistance and type 2 diabetes mellitus. Whilst current studies appear to re-affirm the role of resistin on glucose homeostasis in rodent systems, we are still unravelling the functionality of resistin in human biology in respect to glucose metabolism and insulin signalling. This review will summarize the current knowledge, put into context the developments to date and discuss the controversial points. RECENT FINDINGS: Current evidence appears to suggest that resistin is a pro-inflammatory cytokine. Thus, like many other adipocytokines, resistin may possess a dual role in contributing to metabolic disease: first through its direct effects on substrate metabolism and second, through regulating inflammation within its target tissues. The chemistry of resistin has also been the subject of investigation and like adiponectin, the homo-oligomerization of this protein has a bearing on its function. SUMMARY: The most recent advances include the identification of circulating higher molecular weight structures of resistin in both rodent and human serum. This has been complemented by work casting light on the function and purpose of multimeric resistin in mice. Resistin appears to have effects on substrate metabolism through impairment of insulin action, particularly in the liver, but in addition, also has effects on insulin independent pathways.

Animals↗

PubMed2005

Role of resistin in obesity, insulin resistance and Type II diabetes.

Resistin is a member of a class of cysteine-rich proteins collectively termed resistin-like molecules. Resistin has been implicated in the pathogenesis of obesity-mediated insulin resistance and T2DM (Type II diabetes mellitus), at least in rodent models. In addition, resistin also appears to be a pro-inflammatory cytokine. Taken together, resistin, like many other adipocytokines, may possess a dual role in contributing to disease risk. However, to date there has been considerable controversy surrounding this 12.5 kDa polypeptide in understanding its physiological relevance in both human and rodent systems. Furthermore, this has led some to question whether resistin represents an important pathogenic factor in the aetiology of T2DM and cardiovascular disease. Although researchers still remain divided as to the role of resistin, this review will place available data on resistin in the context of our current knowledge of the pathogenesis of obesity-mediated diabetes, and discuss key controversies and developments.

Amino Acid Sequence↗