67,396 research outputs found
Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling.
No full textlucose effectiveness is an important determinant of glucose tolerance that can be derived from minimal model analysis of an intravenous glucose tolerance test (IVGTT). However, recent evidence suggests that glucose effectiveness is overestimated by minimal model analysis. Here we compare a new model-independent estimate of glucose effectiveness with the minimal model estimate by reanalyzing published data in which insulin-dependent diabetic subjects were each given IVGTTs under two conditions (Quon, M. J., C. Cochran, S. I. Taylor, and R. C. Eastman. Diabetes 43: 890-896, 1994). In one case, a basal insulin level was maintained (BI-IVGTT). In the second case, a dynamic insulin response was recreated (DI-IVGTT). Our results show that minimal model glucose effectiveness is very similar to the model-independent measurement during a BI-IVGTT but is three times higher during a DI-IVGTT. To investigate the causes of minimal model overestimation in the presence of a dynamic insulin response, Monte Carlo simulation studies on a two-compartment model of glucose kinetics with various insulin response patterns were performed. Results suggest that minimal model overestimation is due to single-compartment representation of glucose kinetics that results in a critical oversimplification in the presence of increasingly dynamic insulin secretion patterns
Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling
No full textGlucose effectiveness is an important determinant of glucose tolerance that can be derived from minimal model analysis of an intravenous glucose tolerance test (IVGTT). However, recent evidence suggests that glucose effectiveness is overestimated by minimal model analysis. Here we compare a new model-independent estimate of glucose effectiveness with the minimal model estimate by reanalyzing published data in which insulin-dependent diabetic subjects were each given IVGTTs under two conditions (Quon, M. J., C. Cochran, S. I. Taylor, and R. C. Eastman. Diabetes 43: 890-896, 1994). In one case, a basal insulin level was maintained (BI-IVGTT). In the second case, a dynamic insulin response was recreated (DI-IVGTT). Our results show that minimal model glucose effectiveness is very similar to the model- independent measurement during a BI-IVGTT but is three times higher during a DI-IVGTT. To investigate the causes of minimal model overestimation in the presence of a dynamic insulin response, Monte Carlo simulation studies on a two-compartment model of glucose kinetics with various insulin response patterns were performed. Results suggest that minimal model overestimation is due to single-compartment representation of glucose kinetics that results in a critical oversimplification in the presence of increasingly dynamic insulin secretion patterns
A Deformed Quon Algebra
No full textsummary:The quon algebra is an approach to particle statistics in order to provide a theory in which the Pauli exclusion principle and Bose statistics are violated by a small amount. The quons are particles whose annihilation and creation operators obey the quon algebra which interpolates between fermions and bosons. In this paper we generalize these models by introducing a deformation of the quon algebra generated by a collection of operators , , on an infinite dimensional vector space satisfying the deformed -mutator relations . We prove the realizability of our model by showing that, for suitable values of , the vector space generated by the particle states obtained by applying combinations of 's and 's to a vacuum state is a Hilbert space. The proof particularly needs the investigation of the new statistic cinv and representations of the colored permutation group
Role of Lipotoxicity in Endothelial Dysfunction
No full textVascular endothelial dysfunction is determined by both genetic and environmental factors that cause decreased bioavailability of the vasodilator nitric oxide. This is a hallmark of atherosclerosis, hypertension, and coronary heart disease, which are major complications of metabolic disorders, including diabetes and obesity. Several therapeutic interventions, including changes in lifestyle as well as pharmacologic treatments, are useful for improving endothelial dysfunction in the face of lipotoxicity. This review discusses the current understanding of molecular and physiologic mechanisms underlying lipotoxicity-mediated endothelial dysfunction as well as relevant therapeutic approaches to ameliorate dyslipidemia and consequent endothelial dysfunction that have the potential to improve cardiovascular and metabolic outcomes. © 2012 Elsevier Inc
Evidence for the decay B0→J/ψω and measurement of the relative branching fractions of meson decays to J/ψη and J/ψη′
No full textFirst evidence of the B 0 → J / ψ ω decay is found and the B s 0 → J / ψ η and B s 0 → J / ψ η ′ decays are studied using a dataset corresponding to an integrated luminosity of 1.0 fb -1 collected by the LHCb experiment in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV. The branching fractions of these decays are measured relative to that of the B 0 → J / ψ ρ 0 decay:frac(B (B 0 → J / ψ ω), B (B 0 → J / ψ ρ 0)) = 0.89 ± 0.19 (stat) - 0.13 + 0.07 (syst),frac(B (B s 0 → J / ψ η), B (B 0 → J / ψ ρ 0)) = 14.0 ± 1.2 (stat) - 1.5 + 1.1 (syst) - 1.0 + 1.1 (frac(f d, f s)),frac(B (B s 0 → J / ψ η ′), B (B 0 → J / ψ ρ 0)) = 12.7 ± 1.1 (stat) - 1.3 + 0.5 (syst) - 0.9 + 1.0 (frac(f d, f s)), where the last uncertainty is due to the knowledge of f d / f s, the ratio of b-quark hadronization factors that accounts for the different production rate of B 0 and B s 0 mesons. The ratio of the branching fractions of B s 0 → J / ψ η ′ and B s 0 → J / ψ η decays is measured to befrac(B (B s 0 → J / ψ η ′), B (B s 0 → J / ψ η)) = 0.90 ± 0.09 (stat) - 0.02 + 0.06 (syst)
ACTIVATION OF ENOS BY INSULIN IS INDEPENDENT OF CA++ BUT REQUIRES PHOSPHORYLATION BY AKT AT SER1179
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Ghrelin has novel vascular actions that mimic PI 3-kinase-dependent actions of insulin to stimulate production of NO from endothelial cells
No full textGhrelin is an orexigenic peptide hormone secreted by the stomach. In patients with metabolic syndrome and low ghrelin levels, intra-arterial ghrelin administration acutely improves their endothelial dysfunction. Therefore, we hypothesized that ghrelin activates endothelial nitric oxide synthase (eNOS) in vascular endothelium, resulting in increased production of nitric oxide (NO) using signaling pathways shared in common with the insulin receptor. Similar to insulin, ghrelin acutely stimulated increased production of NO in bovine aortic endothelial cells (BAEC) in primary culture (assessed using NO-specific fluorescent dye 4,5-diaminofluorescein) in a time- and dose-dependent manner. Production of NO in response to ghrelin (100 nM, 10 min) in human aortic endothelial cells was blocked by pretreatment of cells with NG-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), wortmannin [phosphatidylinositol (PI) 3-kinase inhibitor], or (D-Lys3)-GHRP-6 (selective antagonist of ghrelin receptor GHSR-1a), as well as by knockdown of GHSR-1a using small-interfering (si) RNA (but not by mitogen/extracellular signal-regulated kinase inhibitor PD-98059). Moreover, ghrelin stimulated increased phosphorylation of Akt (Ser473) and eNOS (Akt phosphorylation site Ser1179) that was inhibitable by knockdown of GHSR-1a using siRNA or by pretreatment of cells with wortmannin but not with PD-98059. Ghrelin also stimulated phosphorylation of mitogen-activated protein (MAP) kinase in BAEC. However, unlike insulin, ghrelin did not stimulate MAP kinase-dependent secretion of the vasoconstrictor endothelin-1 from BAEC. We conclude that ghrelin has novel vascular actions to acutely stimulate production of NO in endothelium using a signaling pathway that involves GHSR-1a, PI 3-kinase, Akt, and eNOS. Our findings may be relevant to developing novel therapeutic strategies to treat diabetes and related diseases characterized by reciprocal relationships between endothelial dysfunction and insulin resistance
Letter from Carl Hayden to M. J. Riordan
No full textLetter from Carl Hayden to M. J. Riordan expressing his support for Coconino County in turning over the Bright Angel Trail to the federal government
Insulin receptor substrate-1, and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial RID B-1970-2008
No full textVasodilator actions of insulin are mediated by signaling
pathways involving phosphatidylinositol 3-kinase
(PI 3-kinase) and Akt that lead to activation of endothelial
nitric oxide synthase (eNOS) in endothelium.
Signaling molecules immediately upstream and
downstream from PI 3-kinase involved with production
of NO in response to insulin have not been previously
identified. In this study, we evaluated roles of
insulin receptor substrate 1 (IRS-1) and phosphoinositide-
dependent kinase 1 (PDK-1) in production
of NO. The fluorescent dye 4,5-diamine fluorescein
diacetate was used to directly measure NO in NIH-
3T3IR cells transiently cotransfected with eNOS and
various IRS-1 or PDK-1 constructs. In control cells,
transfected with only eNOS, insulin stimulated a
rapid dose-dependent increase in NO. Overexpression
of wild-type IRS-1 increased the maximal insulin
response 3-fold. Overexpression of IRS1-F6 (mutant
that does not bind PI 3-kinase) or an antisense ribozyme
against IRS-1 substantially inhibited insulinstimulated
production of NO. Likewise, overexpression
of wild-type PDK-1 enhanced insulin-stimulated
production of NO, whereas a kinase-inactive mutant
PDK-1 inhibited this action of insulin. Qualitatively
similar results were observed in vascular endothelial
cells. Production of NO by a calcium-dependent
mechanism in response to lysophosphatidic acid
was unaffected by either wild-type or mutant IRS-1
and PDK-1. We conclude that IRS-1 and PDK-1 play
necessary roles in insulin-signaling pathways leading
to activation of eNOS. Furthermore, classical Ca2-
mediated pathways for activation of eNOS are separable
from IRS-1- and PDK-1-dependent insulinsignaling
pathways
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