American journal of physiology. Endocrinology and metabolism
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Am. J. Physiol. Endocrinol. Metab. · Oct 2004
Clinical TrialMinimal model estimation of glucose absorption and insulin sensitivity from oral test: validation with a tracer method.
Measuring insulin sensitivity during the physiological milieu of oral glucose perturbation, e.g., a meal or an oral glucose tolerance test, would be extremely valuable but difficult since the rate of appearance of absorbed glucose is unknown. The reference method is a tracer two-step one: first, the rate of appearance of glucose (R(a meal)(ref)) is reconstructed by employing the tracer-to-tracee ratio clamp technique with two tracers and a model of non-steady-state glucose kinetics; next, this R(a meal)(ref) is used as the known input of a model describing insulin action on glucose kinetics to estimate insulin sensitivity (SI(ref)). Recently, a nontracer method based on the oral minimal model (OMM) has been proposed to estimate simultaneously the above quantities, denoted R(a meal) and SI, respectively, from plasma glucose and insulin concentrations measured after an oral glucose perturbation. ⋯ It is thus important to establish whether or not the "nontracer" R(a meal) and SI compare well with the "tracer" R(a meal)(ref) and SI(ref). We do this comparison on a database of 88 subjects, and it is very satisfactory: R(a meal) profiles agree well with the R(a meal)(ref) and correlation of SI(ref) with SI is r = 0.86 (P < 0.0001). We conclude that OMM candidates as a reliable tool to measure both the rate of glucose absorption and insulin sensitivity from oral glucose tests without employing tracers.
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Am. J. Physiol. Endocrinol. Metab. · Sep 2004
Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice.
Growth hormone, acting through its receptor (GHR), plays an important role in carbohydrate metabolism and in promoting postnatal growth. GHR gene-deficient (GHR(-/-)) mice exhibit severe growth retardation and proportionate dwarfism. To assess the physiological relevance of growth hormone actions, GHR(-/-) mice were used to investigate their phenotype in glucose metabolism and pancreatic islet function. ⋯ This reduction in pancreatic islet mass appears to be related to decreases in proliferation and cell growth. GHR(-/-) mice were different from the human Laron syndrome in serum insulin level, insulin responsiveness, and obesity. We conclude that growth hormone signaling is essential for maintaining pancreatic islet size, stimulating islet hormone production, and maintaining normal insulin sensitivity and glucose homeostasis.
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Am. J. Physiol. Endocrinol. Metab. · Aug 2004
Comparative StudyActivity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR.
Activation of AMP-activated protein kinase (AMPK) by exercise and metformin is beneficial for the treatment of type 2 diabetes. We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). We have also reported that LKB1 activates 11 other AMPK-related kinases. ⋯ Contraction, phenformin, or AICAR did not significantly increase activities or expression of the AMPK-related kinases QSK, QIK, MARK2/3, and MARK4 in skeletal muscle. The results of this study suggest that muscle contraction, phenformin, or AICAR activates AMPK by a mechanism that does not involve direct activation of LKB1. They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases.
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Am. J. Physiol. Endocrinol. Metab. · Jul 2004
Randomized Controlled Trial Clinical TrialTotal branched-chain amino acids requirement in patients with maple syrup urine disease by use of indicator amino acid oxidation with L-[1-13C]phenylalanine.
Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by defects in the mitochondrial multienzyme complex branched-chain alpha-keto acid dehydrogenase (BCKD; EC 1.2.4.4), responsible for the oxidative decarboxylation of the branched-chain ketoacids (BCKA) derived from the branched-chain amino acids (BCAA) leucine, valine, and isoleucine. Deficiency of the enzyme results in increased concentrations of the BCAA and BCKA in body cells and fluids. The treatment of the disease is aimed at keeping the concentration of BCAA below the toxic concentrations, primarily by dietary restriction of BCAA intake. ⋯ Total BCAA requirement was determined by measuring the oxidation of l-[1-(13)C]phenylalanine to (13)CO(2). The mean total BCAA requirement was estimated using a two-phase linear regression crossover analysis, which showed that the mean total BCAA requirement was 45 mg.kg(-1).day(-1), with the safe level of intake (upper 95% confidence interval) at 62 mg.kg(-1).day(-1). This is the first time BCAA requirements in patients with MSUD have been determined directly.
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Am. J. Physiol. Endocrinol. Metab. · Apr 2004
ReviewTen categories of statistical errors: a guide for research in endocrinology and metabolism.
A simple framework is introduced that defines ten categories of statistical errors on the basis of type of error, bias or imprecision, and source: sampling, measurement, estimation, hypothesis testing, and reporting. Each of these ten categories is illustrated with examples pertinent to research and publication in the disciplines of endocrinology and metabolism. Some suggested remedies are discussed, where appropriate. A review of recent issues of American Journal of Physiology: Endocrinology and Metabolism and of Endocrinology finds that very small sample sizes may be the most prevalent cause of statistical error in this literature.