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  • 1
    Keywords: brain ; RECEPTOR ; CELL ; Germany ; KINASE ; EXPOSURE ; NEW-YORK ; PATIENT ; INDEX ; treatment ; cell culture ; culture ; TRIAL ; PLASMA ; DECREASE ; ATP ; SKELETAL-MUSCLE ; GLUCOSE ; DOUBLE-BLIND ; OXIDATIVE STRESS ; SMOKERS ; OXYGEN ; insulin ; INSULIN-RECEPTOR ; 3T3-L1 ADIPOCYTES ; CREATINE SUPPLEMENTATION ; HYDROGEN-PEROXIDE PRODUCTION ; LOW-CARBOHYDRATE ; obesity,hyperlipidemia,body fat,insulin reactivity,thiol antioxidant treatment ; REDOX STATE ; REVERSES ENDOTHELIAL DYSFUNCTION ; STRESS IMPAIRS INSULIN ; SUPPLEMENTATION ; TYROSINE KINASE DOMAIN
    Abstract: Insulin signaling is enhanced by moderate concentrations of reactive oxygen species (ROS) and suppressed by persistent exposure to ROS. Diabetic patients show abnormally high ROS levels and a decrease in insulin reactivity which is ameliorated by antioxidants, such as N-acetylcysteine (NAC). A similar effect of NAC has not been reported for non-diabetic subjects. We now show that the insulin receptor (IR) kinase is inhibited in cell culture by physiologic concentrations of cysteine. In two double-blind trials involving a total of 140 non-diabetic subjects we found furthermore that NAC increased the HOMA-R index (derived from the fasting insulin and glucose concentrations) in smokers and obese patients, but not in nonobese non-smokers. In obese patients NAC also caused a decrease in glucose tolerance and body fat mass. Simultaneous treatment with creatine, a metabolite utilized by skeletal muscle and brain for the interconversion of ADP and ATP, reversed the NAC-mediated increase in HOMA-R index and the decrease in glucose tolerance without preventing the decrease in body fat. As the obese and hyperlipidemic patients had lower plasma thiol concentrations than the normolipidemic subjects, our results suggest that low thiol levels facilitate the development of obesity. Supplementation of thiols plus creatine may reduce body fat without compromising glucose tolerance
    Type of Publication: Journal article published
    PubMed ID: 15007512
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  • 2
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Human apolipoproteins (apo) E and apo A-IV are polymorphic with significantly different allele frequencies among different ethnic groups. Whereas the variation at the apo E gene locus affects plasma cholesterol levels in all populations studied so far and is associated with longevity in Caucasians, the influence of the common apo A-IV polymorphism on plasma lipoproteins has not been unanimously accepted. We have therefore determined the common apo E and apo A-IV polymorphisms by isoelectric focusing, calculated the respective allele frequencies and studied their effects on plasma lipoproteins in a random sample of 240 nonrelated Turkish subjects (141 males, 99 females) living in Germany and originating from central and eastern Anatolia. When compared with the German population and other Caucasians in Europe a prominence of the apo ɛ3 allele frequency (0.885) was accompanied by a decrease in the frequencies of both the apo ɛ2 allele (0.048) and the apo ɛ4 allele (0.067). Thus, the Turkish population studied here clustered with populations mainly from southern Europe and Japan, which have low ɛ2 and ɛ4 allele frequencies. Also, the frequency of the A-IV-1 allele was higher (0.967) and that of the A-IV-2 allele lower (0.033) in the Turkish subjects studied than in other populations. At an average level of total cholesterol of 194.5 ± 45 mg/dl, no significant influence of the A-IV alleles on plasma lipoproteins was seen. However, apo E and apo B differed significantly between apo E phenotypes, with high levels of apo E and low levels of cholesterol and apo B in carriers of the ɛ2 allele, and vice versa for the ɛ4 allele. The average cholesterol excess for the ɛ2 allele was –7.95 mg/dl, for the ɛ3 allele, –1.34, and for the ɛ4 allele, +14.15 mg/dl. Thus, despite the unusual frequency distribution of the apo E alleles, their effects on plasma lipoproteins are within the range reported for other populations in Europe.
    Type of Medium: Electronic Resource
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