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. · Oct 2004
IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1.
Muscle atrophy results primarily from accelerated protein degradation and is associated with increased expression of two muscle-specific ubiquitin ligases (E3s): atrogin-1 and muscle ring finger 1 (MuRF1). Glucocorticoids are essential for many types of muscle atrophy, and their effects are opposite to those of insulin-like growth factor I (IGF-I) and insulin, which promote growth. In myotubes, dexamethasone (Dex) inhibited growth and enhanced breakdown of long-lived cell proteins, especially myofibrillar proteins (as measured by 3-methylhistidine release), while also increasing atrogin-1 and MuRF1 mRNA. ⋯ Changes in overall proteolysis with Dex and IGF-I correlated tightly with changes in atrogin-1 mRNA content, but not with changes in MuRF1 mRNA. IGF-I activates the phosphatidylinositol 3-kinase (PI3K)-Akt pathway, and inhibition of this pathway [but not the calcineurin-nuclear factor of activated T cell (NFAT) or the MEK-ERK pathway] increased proteolysis and atrogin-1 mRNA expression. Thus an important component of growth stimulation by IGF-I, through the PI3K-Akt pathway, is its ability to rapidly suppress transcription of the atrophy-related E3 atrogin-1 and other atrogenes and degradation of myofibrillar proteins.