YongHoon Kwon

CXCL12 secreted from adipose tissue recruits macrophages and induces insulin resistance in mice

Aims/hypothesisObesity-induced inflammation is initiated by the recruitment of macrophages into adipose tissue. The recruited macrophages, called adipose tissue macrophages, secrete several proinflammatory cytokines that cause low-grade systemic inflammation and insulin resistance. The aim of this study was to find macrophage-recruiting factors that are thought to provide a crucial connection between obesity and insulin resistance.MethodsWe used chemotaxis assay, reverse phase HPLC and tandem MS analysis to find chemotactic factors from adipocytes. The expression of chemokines and macrophage markers was evaluated by quantitative RT-PCR, immunohistochemistry and FACS analysis.ResultsWe report our finding that the chemokine (C-X-C motif) ligand 12 (CXCL12, also known as stromal cell-derived factor 1), identified from 3T3-L1 adipocyte conditioned medium, induces monocyte migration via its receptor chemokine (C-X-C motif) receptor 4 (CXCR4). Diet-induced obese mice demonstrated a robust increase of CXCL12 expression in white adipose tissue (WAT). Treatment of obese mice with a CXCR4 antagonist reduced macrophage accumulation and production of proinflammatory cytokines in WAT, and improved systemic insulin sensitivity.Conclusions/interpretationIn this study we found that CXCL12 is an adipocyte-derived chemotactic factor that recruits macrophages, and that it is a required factor for the establishment of obesity-induced adipose tissue inflammation and systemic insulin resistance.

A Collocation Method for the Gurtin--MacCamy Equation with Finite Life-Span

A collocation method along the characteristics for a stiff problem arising from population dynamics is proposed and analyzed. It is a fourth order implicit Runge--Kutta method of two stage to the integration of the ODE along the characteristics, whose collocation points are zeros of the linearly transformed Legendre monic polynomial. Nonnegativity of the numerical solutions is shown. The stability of the method is discussed. It is proven that the scheme is convergent at a fourth order rate in the maximum norm. Several numerical examples are presented.

Emodin Regulates Glucose Utilization by Activating AMP-activated Protein Kinase

Background: AMPK activation improves glucose tolerance and insulin sensitivity. Results: Emodin increases glucose uptake in skeletal muscle and lowers blood glucose levels via AMPK activation. Conclusion: Administration of emodin leads to increased glucose tolerance and insulin sensitivity in vivo. Significance: Our results highlight the potential value of emodin as a drug for the treatment of diabetes. AMP-activated protein kinase has been described as a key signaling protein that can regulate energy homeostasis. Here, we aimed to characterize novel AMP-activated kinase (AMPK)-activating compounds that have a much lower effective concentration than metformin. As a result, emodin, a natural anthraquinone derivative, was shown to stimulate AMPK activity in skeletal muscle and liver cells. Emodin enhanced GLUT4 translocation and [14C]glucose uptake into the myotube in an AMPK-dependent manner. Also, emodin inhibited glucose production by suppressing the expression of key gluconeogenic genes, such as phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, in hepatocytes. Furthermore, we found that emodin can activate AMPK by inhibiting mitochondrial respiratory complex I activity, leading to increased reactive oxygen species and Ca2+/calmodulin-dependent protein kinase kinase activity. Finally, we confirmed that a single dose administration of emodin significantly decreased the fasting plasma glucose levels and improved glucose tolerance in C57Bl/6J mice. Increased insulin sensitivity was also confirmed after daily injection of emodin for 8 days using an insulin tolerance test and insulin-stimulated PI3K phosphorylation in wild type and high fat diet-induced diabetic mouse models. Our study suggests that emodin regulates glucose homeostasis in vivo by AMPK activation and that this may represent a novel therapeutic principle in the treatment of type 2 diabetic models.

A Second-order Finite Difference Method for Option Pricing Under Jump-diffusion Models

We develop a finite difference method to solve partial integro-differential equations which describe the behavior of option prices under jump-diffusion models. With localization to a bounded domain of the spatial variable, these equations are discretized on uniform grid points over a finite domain of time and spatial variables. The proposed method is based on three time levels and leads to linear systems with tridiagonal matrices. In this paper the stability of the proposed method and the second-order convergence rate with respect to a discrete

Second-order accurate difference methods for a one-sex model of population dynamics

\ell^{2}

A Second-Order Tridiagonal Method for American Options under Jump-Diffusion Models

-norm are proved. Numerical results obtained with European put options under the Merton and Kou models show the behaviors of the stability and the second-order convergence rate.

A flexible inverse laplace transform algorithm and its application

A first-order hyperbolic equation of age and time variables describes a one-sex model of population dynamics. The second-order finite difference method in the characteristic (age,time) direction is used to approximate simultaneously both the age distribution

Gut microbe-derived extracellular vesicles induce insulin resistance, thereby impairing glucose metabolism in skeletal muscle

u(x,t)

Proteomic Analysis of the Palmitate-induced Myotube Secretome Reveals Involvement of the Annexin A1-Formyl Peptide Receptor 2 (FPR2) Pathway in Insulin Resistance

of the solution and the total population

Estimation of local volatilities in a generalized Black-Scholes model

P(t)