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Sell H.,Paul Langerhans Group Integrative Physiology
Methods in molecular biology (Clifton, N.J.) | Year: 2012

Glucose disposal in skeletal muscle is a major target for insulin action and assessment of insulin-regulated glucose uptake under in vitro conditions allows the direct determination of insulin sensitivity in this organ. For this purpose, a variety of muscle preparations from different parts of the body can be used. We describe here a detailed protocol for using epitrochlearis muscle strips and additionally for using primary skeletal muscle cells. Source


Greulich S.,Institute of Clinical Biochemistry and Pathobiochemistry | Maxhera B.,German Diabetes Center | Maxhera B.,Heinrich Heine University Dusseldorf | Vandenplas G.,Ghent University | And 12 more authors.
Circulation | Year: 2012

Background-: Secreted factors from epicardial adipose tissue (EAT) have been implicated in the development of cardiomyocyte dysfunction. This study aimed to assess whether alterations in the secretory profile of EAT in patients with type 2 diabetes mellitus (DM2) affect contractile function and insulin action in cardiomyocytes. Methods and Results-: Contractile function and insulin action were analyzed in primary adult rat cardiomyocytes incubated with conditioned media (CM) generated from explants of EAT biopsies obtained from patients without and with DM2. CM from subcutaneous and pericardial adipose tissue biopsies from the same patients served as the control. Cardiomyocytes treated with CM (EAT) from DM2 patients showed reductions in sarcomere shortening, cytosolic Ca fluxes, expression of sarcoplasmic endoplasmic reticulum ATPase 2a, and decreased insulin-mediated Akt-Ser473-phosphorylation as compared with CM from the other groups. Profiling of the CM showed that activin A, angiopoietin-2, and CD14 selectively accumulated in CM-EAT-DM2 versus CM-EAT in patients without DM2 and CM from the other fat depots. Accordingly, EAT biopsies from DM2 patients were characterized by clusters of CD14-positive monocytes. Furthermore, SMAD2-phosphorylation, a downstream target of activin A signaling, was elevated in cardiomyocytes treated with CM (EAT) from DM2 patients, and the detrimental effects of CM (EAT) from DM2 patients were partially abolished in cardiomyocytes pretreated with a neutralizing antibody against activin A. Finally, both recombinant activin A and angiopoietin-2 reduced cardiomyocyte contractile function, but only activin A reduced the expression of sarcoplasmic endoplasmic reticulum ATPase 2a. Conclusions-: Collectively, our data implicate DM2-related alterations in the secretory profile of EAT in the pathogenesis of diabetes mellitus-related heart disease. © 2012 American Heart Association, Inc. Source


Burghoff S.,Heinrich Heine University Dusseldorf | Flogel U.,Heinrich Heine University Dusseldorf | Bongardt S.,Heinrich Heine University Dusseldorf | Burkart V.,Institute for Clinical Diabetology | And 8 more authors.
Archives of Physiology and Biochemistry | Year: 2013

Context: CD73 converts extracellular AMP to adenosine which is well known to inhibit lipolysis. It is unknown, however, whether adenosine formed directly by CD73 is functionally relevant in this process. Objective: We therefore explored the effect of CD73-derived adenosine on body fat of aged mice. Results: In lean mice, extracellular adenosine formation by adipocytes is dependent on CD73. High fat diet down-regulates the expression of CD73 in wildtype mice similar to ob/ob mice. Transgenic mice chronically lacking CD73 (CD73 -/-) gain significantly less body weight and show decreased superficial white fat content as well as increased serum free fatty acids and triglycerides. In addition, intramyocellular lipid levels are significantly increased. This phenotype is accompanied by an increase in blood glucose and serum insulin levels although insulin secretion and the level of insulin degrading enzyme are unaltered. Additionally, insulin-induced Akt phosphorylation is reduced in skeletal muscle of CD73-/- mice. Conclusion: CD73-derived adenosine is functionally involved in body fat homeostasis. © 2013 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted. Source


Sell H.,Paul Langerhans Group Integrative Physiology | Bluher M.,University of Leipzig | Kloting N.,University of Leipzig | Schlich R.,Paul Langerhans Group Integrative Physiology | And 10 more authors.
Diabetes Care | Year: 2013

Objective-To study expression of the recently identified adipokine dipeptidyl peptidase-4 (DPP4) in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of patients with various BMIs and insulin sensitivities, as well as to assess circulating DPP4 in relation to obesity and insulin sensitivity. Research design and methods-DPP4 expression was measured in SAT and VAT from 196 subjects with a wide range of BMIs and insulin sensitivities. DPP4 release was measured ex vivo in paired biopsies from SAT and VAT as well as in vivo from SAT of lean and obese patients. Circulating DPP4 was measured in insulin-sensitive and insulin-resistant BMImatched obese patients. Results-DPP4 expression was positively correlated with BMI in both SAT and VAT, with VAT consistently displaying higher expression than SAT. Ex vivo release of DPP4 from adipose tissue explants was higher in VAT than in SAT in both lean and obese patients, with obese patients displaying higher DPP4 release than lean controls. Net release of DPP4 from adipose tissue was also demonstrated in vivo with greater release in obese subjects than in lean subjects and in women than in men. Insulin-sensitive obese patients had significantly lower circulating DPP4 than did obesity-matched insulin-resistant patients. In this experiment, DPP4 positively correlated with the amount of VAT, adipocyte size, and adipose tissue inflammation. Conclusions-DPP4, a novel adipokine, has a higher release fromVAT that is particularly pronounced in obese and insulin-resistant patients. Our data suggest that DPP4 may be a marker for visceral obesity, insulin resistance, and the metabolic syndrome. © 2013 by the American Diabetes Association. Source


Sell H.,Paul Langerhans Group Integrative Physiology | Jensen J.,Norwegian School of Sport Sciences | Eckel J.,Paul Langerhans Group Integrative Physiology
Methods in Molecular Biology | Year: 2012

Glucose disposal in skeletal muscle is a major target for insulin action and assessment of insulin-regulated glucose uptake under in vitro conditions allows the direct determination of insulin sensitivity in this organ. For this purpose, a variety of muscle preparations from different parts of the body can be used. We describe here a detailed protocol for using epitrochlearis muscle strips and additionally for using primary skeletal muscle cells. © 2012 Springer Science+Business Media, LLC. Source

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