Identificador: TDX:527
Autores: Broch i Montané, Montserrat
Resumen:
Type 2 diabetes mellitus (DM2) was caused basically by the reduction of the insulin action (insulin resistance) and by the deterioration of the beta cells function. The DM2 and obesity are intimately related between them. In this way, the adipose tissue is able to synthesize and secrete various molecules that are related to the insulin sensitivity (Si) modulation such as Tumor Necrosis Factor-alfa (TNF) and interleukin-6 (IL-6).TNF- signals thorough at least two known cell-surface receptors: TNFR1 and TNFR2. The joining of the cytokine to their receptors derived to receptors soluble forms (sTNFR1 and sTNFR2). 'In vivo' studies, cytokine supply could inhibit the insulin-stimulated glucose uptake. In genetic fat and /or diabetics animals there is an over-expression of this cytokine in fat tissue and in plasma.In obese patients, there is an over-expression of TNF and TNFR2 in fat tissue and of sTNFR2 in plasma. These over-expressions are related to the body mass index and insulin levels, both markers of insulin resistance.On the other hand, the IL-6 induces to hypertrygliceridemia 'in vivo' and 'in vitro'.In humans, this cytokine is over-expressed in obese and DM2 patients and it is involved in the classical insulin resistance markers. G-allele of the -174G>C polymorphism has been found to be associated with elevated transcription rates.The goals of the presented studies are to analyse TNF system and IL-6 and their relation to insulin sensitivity.1. Plasma levels of the soluble fraction of tumor necrosis factor receptor 2 and insulin resistance. Diabetes, 47:1757-62, 1998Obese patients (BMI >30 < 40 kg/m2) showed increased plasma levels of sTNFR2 in comparison with lean. These levels are correlated positively with BMI, fat free mass and glucose levels; and related negatively with insulin sensitivity.2. Polymorphism of the tumor necrosis factor receptor 2 gene is associated with obesity, leptin levels, and insulin resistance in young subjects and diettreated type 2 diabetic patients. Diabetes Care, 23:831-837, 2000 3´ Untranslated region of the TNFR2 gene was analysed in DM2 and control populations. It was found four alleles identified by sequencing analysis. A2 allele exhibited significantly higher BMI and leptin levels in young population (younger than 54 years-old). In a subgroup of control subjects it was found that people with A2 allele showed several characteristics of the insulin resistance syndrome such as increased waist-to-hit ratio and hypertrygliceridemia in association with a lower insulin sensitivity index.3. Interleukin-6 gene polymorphism and insulin sensitivity. Diabetes, 49:517- 520, 2000It was analysed the -174G>C polymorphism IL-6 gene in obese patients (BMI<40 kg/m2). Subjects with G allele, despite the fact of being similar in age, fat mass and fat free mass in comparison with carrier of C allele, the first one showed significantly higher levels of blood HbA1c , insulin and glucose and lower Si 4. Interleukin-6 gene polymorphism and lipid abnormalities in healthy subjects. J Clin Endocrinol Metab 85:1334-1339, 2000The same population than in the previous study was characterised through a lipidic profile and IL-6 levels were measured. Subjects carrying the G allele showed higher plasma levels of triglycerides and free fatty acids before and post OGTT test. Plasma IL-6 levels were significantly associated with these lipidic parameters.Conclusions1.- The measure of plasma sTNFR2 levels may be used as an insulin sensitivity marker2.- 3´untranslated region of TNFR2 gene may be used as a genetic marker associated with metabolic syndrome3.- -174G>C restriction polymorphism of IL-6 gene may be related with genetic predisposition to insulin sensitivity rate and to plasma lipids levels.
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