Search Results
You are looking at 1 - 4 of 4 items for
- Author: Stefan R Bornstein x
- Refine by access: All content x
Search for other papers by Charlotte Steenblock in
Google Scholar
PubMed
Search for other papers by Nicole Bechmann in
Google Scholar
PubMed
Search for other papers by Felix Beuschlein in
Google Scholar
PubMed
Search for other papers by Christian Wolfrum in
Google Scholar
PubMed
Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zürich, Switzerland
School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, UK
Search for other papers by Stefan R Bornstein in
Google Scholar
PubMed
Obesity is associated with a higher risk of severe coronavirus disease 2019 (COVID-19) and increased mortality. In the current study, we have investigated the expression of ACE2, NRP1, and HMGB1, known to facilitate severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cell entry, in adipose tissue from non-COVID-19 control patients with normal weight, overweight, and obesity. All factors were expressed, but no significant differences between the groups were observed. Furthermore, diabetes status and medications did not affect the expression of ACE2. Only in obese men, the expression of ACE2 in adipose tissue was higher than in obese women. In the adipose tissue from patients who died from COVID-19, SARS-CoV-2 was detected in the adipocytes even though the patients died more than 3 weeks after the acute infection. This suggests that adipocytes may act as reservoirs for the virus. In COVID-19 patients, the expression of NRP1 was increased in COVID-19 patients with overweight and obesity. Furthermore, we observed an increased infiltration with macrophages in the COVID-19 adipose tissues compared to control adipose tissue. In addition, crown-like structures of dying adipocytes surrounded by macrophages were observed in the adipose tissue from COVID-19 patients. These data suggest that in obese individuals, in addition to an increased mass of adipose tissue that could potentially be infected, increased macrophage infiltration due to direct infection with SARS-CoV-2 and sustained viral shedding, rather than preinfection ACE2 receptor expression, may be responsible for the increased severity and mortality of COVID-19 in patients with obesity.
Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
Search for other papers by Manuel Gado in
Google Scholar
PubMed
Search for other papers by Eva Tsaousidou in
Google Scholar
PubMed
Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
Diabetes and Nutritional Sciences, King's College London, London, UK
Search for other papers by Stefan R Bornstein in
Google Scholar
PubMed
Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
Search for other papers by Nikolaos Perakakis in
Google Scholar
PubMed
Sexual dimorphism in energy metabolism is now established and suggested to affect many aspects of metabolic diseases and in particular diabetes and obesity. This is strongly related to sex-based differences in whole-body insulin resistance. Women are more insulin sensitive compared to men, but this metabolic advantage gradually disappears after menopause or when insulin resistance progresses to hyperglycemia and diabetes. In this narrative review, first, we describe the pathophysiology related to insulin resistance and then we present the epidemiological evidence as well as the important biological factors that play a crucial role in sexual dimorphism in insulin sensitivity. We focus particularly on the differences in body fat and muscle mass distribution and function, in inflammation and in sex hormones between males and females. Most importantly, we describe the significant mechanistic differences in insulin sensitivity as well as glucose and lipid metabolism in key metabolic organs: liver, white adipose tissue, and skeletal muscle. Finally, we present the sex-based differences in response to different interventions and discuss important open research questions.
Search for other papers by Steffi Kopprasch in
Google Scholar
PubMed
Search for other papers by Jens Pietzsch in
Google Scholar
PubMed
Search for other papers by Ishrath Ansurudeen in
Google Scholar
PubMed
Search for other papers by Juergen Graessler in
Google Scholar
PubMed
Search for other papers by Alexander W Krug in
Google Scholar
PubMed
Search for other papers by Monika Ehrhart-Bornstein in
Google Scholar
PubMed
Search for other papers by Stefan R Bornstein in
Google Scholar
PubMed
Modification of low-density lipoprotein (LDL) and abnormal aldosterone and cortisol metabolism have been implicated in the pathogenesis of type 2 diabetes (DM2) and diabetic vascular disease. Since LDL serves as a major cholesterol source for adrenal steroidogenesis, we investigated whether LDL modification in prediabetic and diabetic subjects influences adrenocortical aldosterone and cortisol release. LDL was isolated from 30 subjects with normal glucose tolerance (NGT-LDL), 30 subjects with impaired glucose tolerance (IGT-LDL), and 26 patients with DM2 (DM2-LDL). Oxidation and glycoxidation characteristics of LDL apolipoprotein B100 of each individual was assessed by gas chromatography–mass spectrometry analysis. Human adrenocortical cells (NCI-H295R) were incubated for 24 h with 100 μg/ml LDL and after removal of supernatants stimulated for a further 24 h with angiotensin II (AngII). In supernatants, aldosterone and cortisol secretion was measured. IGT-LDL and DM2-LDL were substantially more modified than NGT-LDL. Each of the five measured oxidation/glycoxidation markers was significantly positively associated with glycemic control, measured as HbA1c. LDL from all subjects stimulated both the basal and AngII-induced aldosterone and cortisol release from adrenocortical cells. However, hormone secretion was significantly inversely related to the degree of LDL oxidation/glycoxidation. We conclude that LDL modifications in IGT and DM2 subjects may have significant clinical benefits by counteracting prediabetic and diabetic overactivity of the renin–angiotensin–aldosterone system and enhanced cortisol generation.
University of Technology Dresden, University Clinic III, Dresden, Germany
School of Medicine, Department of Histology and Embryology, Poznan, Poland
Search for other papers by Matthias Haase in
Google Scholar
PubMed
University of Technology Dresden, University Clinic III, Dresden, Germany
School of Medicine, Department of Histology and Embryology, Poznan, Poland
Search for other papers by Matthias Schott in
Google Scholar
PubMed
University of Technology Dresden, University Clinic III, Dresden, Germany
School of Medicine, Department of Histology and Embryology, Poznan, Poland
Search for other papers by Stefan R Bornstein in
Google Scholar
PubMed
University of Technology Dresden, University Clinic III, Dresden, Germany
School of Medicine, Department of Histology and Embryology, Poznan, Poland
Search for other papers by Ludwik K Malendowicz in
Google Scholar
PubMed
University of Technology Dresden, University Clinic III, Dresden, Germany
School of Medicine, Department of Histology and Embryology, Poznan, Poland
Search for other papers by Werner A Scherbaum in
Google Scholar
PubMed
University of Technology Dresden, University Clinic III, Dresden, Germany
School of Medicine, Department of Histology and Embryology, Poznan, Poland
Search for other papers by Holger S Willenberg in
Google Scholar
PubMed
CITED2 gene deletion in mice leads to adrenal agenesis. Therefore, we analyzed CITED2, a CBP/p300 interacting transactivator with transforming activity, in the human adrenal gland. In this study, we examined CITED2 expression in human embryonic and adult adrenal glands as well as adrenocortical carcinomas. As ACTH and basic fibroblast growth factor (bFGF) are connected to the physiology and growth of adrenocortical cells we studied the regulation of CITED2 by these factors in the NCI-H295R adrenocortical carcinoma cell line. We found CITED2 expression in the adult adrenal cortex as well in adrenocortical carcinomas. At an early stage of human adrenal organogenesis CITED2 could be located to the definitive zone of the developing adrenal gland using immunohistochemistry. In NCI-H295R cells, stimulation by bFGF led to a dose-dependent increase in CITED2 promotor activity, mRNA and protein expression while ACTH had no significant effect. The stimulatory effect of bFGF could be reduced by blocking mitogen-activated protein kinase activity using the MAPkinase kinase (MEK1)-inhibitor PD98059. CITED2 is expressed in embryonic and adult human adrenal glands as well as in adrenocortical cancer. It is connected to the signaling cascades of bFGF and its expression is modulated by mitogen-activated protein kinases. This suggests a novel role for CITED2 in human adrenal growth and possibly in adrenal tumorigenesis.
