Disruption of Adiponectin Causes Insulin Resistance and Neointimal Formation

Kubota, Naoto; Terauchi, Yasuo; Yamauchi, Toshimasa; Kubota, Tetsuya; Moroi, Masao; Matsui, Junji; Eto, Kazuhiro; Yamashita, Tetsuo; Kamon, Junji; Satoh, Hitomi; Yano, Wataru; Froguel, Philippe; Nagai, Ryozo; Kimura, Satoshi; Kadowaki, Takashi; Noda, Tetsuo

doi:10.1074/jbc.c200251200

Cited by 1,232 publications

(879 citation statements)

References 20 publications

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“…Original adiponectin-deficient mice (C57BL/6 and 129/Sv-mixed background) 63 were backcrossed with C57BL/6 mice more than seven times. Mice were 7-10 weeks old for all experiments.…”

Section: Methodsmentioning

confidence: 99%

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

et al. 2015

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Accumulating epidemiologic evidence has revealed that metabolic syndrome is an independent risk factor for psoriasis development and is associated with more severe psoriasis. Adiponectin, primarily recognized as a metabolic mediator of insulin sensitivity, has been newly drawing attention as a mediator of immune responses. Here we demonstrate that adiponectin regulates skin inflammation, especially IL-17-related psoriasiform dermatitis. Mice with adiponectin deficiency show severe psoriasiform skin inflammation with enhanced infiltration of IL-17-producing dermal Vg4 þ gd-T cells. Adiponectin directly acts on murine dermal gd-T cells to suppress IL-17 synthesis via AdipoR1. We furthermore demonstrate here that the adiponectin level of skin tissue as well as subcutaneous fat is decreased in psoriasis patients. IL-17 production from human CD4-or CD8-positive T cells is also suppressed by adiponectin. Our data provide a regulatory role of adiponectin in skin inflammation, which would imply a mechanism underlying the relationship between psoriasis and metabolic disorders.

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“…Original adiponectin-deficient mice (C57BL/6 and 129/Sv-mixed background) 63 were backcrossed with C57BL/6 mice more than seven times. Mice were 7-10 weeks old for all experiments.…”

Section: Methodsmentioning

confidence: 99%

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

et al. 2015

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“…In brief, after an overnight fast and the collection of baseline samples, Dextrose 0.3 g/kg was administered intravenously, followed 20 min later by the intravenous infusion of insulin 0.03 U/kg (Humulin R; Eli Lilly, Indianapolis, IN, USA). Samples were collected for insulin and glucose at 2, 3, 4, 5,6,8,10,12,14,19,22,23,24,25,27,30,40,50,60,70,80, 90, 100, 120, 140, 160 and 180 min following the dextrose and analysed using the Bergman's Minimal Model, a computer-based method to assess plasma insulin and glucose dynamics during an IVGTT. The minimum model for glucose disposal and insulin dynamics yields assessments of insulin secretion and sensitivity, including the insulin sensitivity index (S I ) and the glucose effectiveness index (S G ) also known as insulin-independent glucose clearance.…”

Section: Subjects Materials and Methodsmentioning

confidence: 99%

“…Persons with type 2 diabetes have lower levels of adiponectin than controls, independent of BMI [7,11]. Heterozygous adiponectin-deficient mice exhibit mild insulin resistance, while homozygous deficiency is associated with more significant glucose intolerance and increased likelihood of diabetes, which can be reversed following adiponectin administration [5,10,12].…”

Section: Introductionmentioning

confidence: 99%

The role of total and high-molecular-weight complex of adiponectin in vascular function in offspring whose parents both had type 2 diabetes

et al. 2005

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Aims/hypothesis: Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. We studied the role played by total adiponectin and by the bioactive high-molecular-weight (HMW) oligomeric complexes of adiponectin in vascular function in offspring whose parents both had type 2 diabetes, a population at high risk of diabetes and atherosclerosis. Methods: Total and %HMW adiponectin, the cytokines C-reactive protein, interleukin-6 and plasminogen activator inhibitor-1 (PAI-1), as well as lipid profiles were assayed in 19 offspring, each with two type 2 diabetic parents. Subjects underwent OGTTs and IVGTTs. Endothelium-dependent vasodilation (EDV) was assessed by brachial artery ultrasonography. Results: There was a significant relationship between %HMW and total adiponectin levels (r=0.72, p=0.001). Despite an expected strong positive correlation between HDL-cholesterol and adiponectin levels (r=0.52, p=0.04), as well as HDL-cholesterol and EDV (r=0.56, p<0.02), there was no significant relationship between either total adiponectin or % HMW adiponectin and EDV. Adiponectin was inversely associated with PAI-1 (r=0.50, p=0.05), but did not correlate with the inflammatory markers C-reactive protein or interleukin-6. Conclusions/interpretation: In offspring of diabetic parents, a population at high risk of diabetes and atherosclerotic disease, there is no relationship between total or %HMW adiponectin and endotheliumdependent vasodilation. However, low adiponectin was associated with impaired fibrinolysis as manifested by increased levels of plasminogen activator inhibitor-1.

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“…We previously demonstrated that adiponectin-deficient (Adipo −/− ) mice exhibit insulin resistance [10], but that after glucose loading the plasma insulin levels tended to be lower in Adipo −/− mice than in wild-type mice, suggesting that adiponectin may induce insulin secretion [10]. The adiponectin receptors ADIPOR1 and ADIPOR2 have recently been cloned [11] and identified in human and rat pancreatic beta cells [12].…”

Section: Introductionmentioning

confidence: 99%

Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration

et al. 2008

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Aims/hypothesis A decrease in plasma adiponectin levels has been shown to contribute to the development of diabetes. However, it remains uncertain whether adiponectin plays a role in the regulation of insulin secretion. In this study, we investigated whether adiponectin may be involved in the regulation of insulin secretion in vivo and in vitro. Methods The effect of adiponectin on insulin secretion was measured in vitro and in vivo, along with the effects of adiponectin on ATP generation, membrane potentials, Ca 2+ currents, cytosolic calcium concentration and state of 5′-AMP-activated protein kinase (AMPK). In addition, insulin granule transport was measured by membrane capacitance and total internal reflection fluorescence (TIRF) analysis.Results Adiponectin significantly stimulated insulin secretion from pancreatic islets to approximately 2.3-fold the baseline value in the presence of a glucose concentration of 5.6 mmol/l. Although adiponectin had no effect on ATP generation, membrane potentials, Ca 2+ currents, cytosolic calcium concentrations or activation status of AMPK, it caused a significant increase of membrane capacitance to approximately 2.3-fold the baseline value. TIRF analysis revealed that adiponectin induced a significant increase in the number of fusion events in mouse pancreatic beta cells under 5.6 mmol/l glucose loading, without affecting the status of previously docked granules. Moreover, intravenous injection of adiponectin significantly increased insulin secretion to approximately 1.6-fold of baseline in C57BL/6 mice. Diabetologia (2008) Conclusions/interpretation The above results indicate that adiponectin induces insulin secretion in vitro and in vivo.

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Disruption of Adiponectin Causes Insulin Resistance and Neointimal Formation

Cited by 1,232 publications

References 20 publications

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

The role of total and high-molecular-weight complex of adiponectin in vascular function in offspring whose parents both had type 2 diabetes

Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration

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