Journal: Diabetologia

Abbreviation

Diabetologia

Publisher

Springer

Journal Volumes

ISSN

1432-0428
0012-186X

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2008 - 200912010 - 201914
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Publications 1 - 10 of 15
  • Dynamics of blood electrolytes in repeated hyper- and/or hypoglycaemic events in patients with type 1 diabetes
    Item type: Journal Article
    Caduff, A.; Lutz, H.U.; Heinemann, L.; et al. (2011)
    Diabetologia
  • Increased Ifi202b/IFI16 expression stimulates adipogenesis in mice and humans
    Item type: Journal Article
    Stadion, Mandy; Schwerbel, Kristin; Graja, Antonia; et al. (2018)
    Diabetologia
    Aims/hypothesis: Obesity results from a constant and complex interplay between environmental stimuli and predisposing genes. Recently, we identified the IFN-activated gene Ifi202b as the most likely gene responsible for the obesity quantitative trait locus Nob3 (New Zealand Obese [NZO] obesity 3). The aim of this study was to evaluate the effects of Ifi202b on body weight and adipose tissue biology, and to clarify the functional role of its human orthologue IFI16. Methods: The impact of Ifi202b and its human orthologue IFI16 on adipogenesis was investigated by modulating their respective expression in murine 3T3-L1 and human Simpson-Golabi-Behmel syndrome (SGBS) pre-adipocytes. Furthermore, transgenic mice overexpressing IFI202b were generated and characterised with respect to metabolic traits. In humans, expression levels of IFI16 in adipose tissue were correlated with several variables of adipocyte function. Results: In mice, IFI202b overexpression caused obesity (Δ body weight at the age of 30 weeks: 10.2 ± 1.9 g vs wild-type mice) marked by hypertrophic fat mass expansion, increased expression of Zfp423 (encoding the transcription factor zinc finger protein [ZFP] 423) and white-selective genes (Tcf21, Tle3), and decreased expression of thermogenic genes (e.g. Cidea, Ucp1). Compared with their wild-type littermates, Ifi202b transgenic mice displayed lower body temperature, hepatosteatosis and systemic insulin resistance. Suppression of IFI202b/IFI16 in pre-adipocytes impaired adipocyte differentiation and triacylglycerol storage. Humans with high levels of IFI16 exhibited larger adipocytes, an enhanced inflammatory state and impaired insulin-stimulated glucose uptake in white adipose tissue. Conclusions/interpretation: Our findings reveal novel functions of Ifi202b and IFI16, demonstrating their role as obesity genes. These genes promote white adipogenesis and fat storage, thereby facilitating the development of obesity-associated insulin resistance.
  • PKBalpha but not PKBbeta can protect human islets from IL-1beta-induced apoptosis
    Item type: Other Conference Item
    Dietrich, Maren G.; Zuellig, Richard A.; Hemmings, Brian A.; et al. (2013)
    Diabetologia
  • Non-invasive glucose monitoring in patients with type 1 diabetes
    Item type: Other Conference Item
    Caduff, A.; Stahel, W. A.; Bull, C.; et al. (2008)
    Diabetologia
  • Multimodal imaging of pancreatic beta cells in vivo by targeting transmembrane protein 27 (TMEM27)
    Item type: Journal Article
    Vats, D.; Wang, H.; Esterhazy, D.; et al. (2012)
    Diabetologia
  • Simultaneous non invasive continuous glucose monitoring on the left and right arm using two multisensor devices
    Item type: Other Conference Item
    Caduff, Andreas; Mueller, M.; De Feo, Oscar; et al. (2010)
    Diabetologia
  • Prospective data evaluation of the application of a multisensor device for non invasive continuous glucose monitoring
    Item type: Other Conference Item
    Talary, Mark S.; Mueller, M.; De Feo, Oscar; et al. (2010)
    Diabetologia
  • Sequential intravital imaging reveals in vivo dynamics of pancreatic tissue transplanted under the kidney capsule in mice
    Item type: Journal Article
    van Gurp, Léon; Loomans, Cindy J.M.; van Krieken, Pim P.; et al. (2016)
    Diabetologia
    Aims/hypothesis Dynamic processes in pancreatic tissue are difficult to study. We aimed to develop an intravital imaging method to longitudinally examine engraftment, vascularisation, expansion and differentiation in mature islets or embryonic pancreases transplanted under the kidney capsule. Methods Isolated pancreatic islets from adult mice and murine embryonic day (E)12.5 pancreases containing fluorescent biomarkers were transplanted under the kidney capsule of immunodeficient recipient mice. Human islet cells were dispersed, transduced with a lentivirus expressing a fluorescent label and reaggregated before transplantation. Graft-containing kidneys were positioned subcutaneously and an imaging window was fitted into the skin on top of the kidney. Intravital imaging using multiphoton microscopy was performed for up to 2 weeks. Volumes of fluorescently labelled cells were determined as a measure of development and survival. Results Transplanted islets and embryonic pancreases showed good engraftment and remained viable. Engraftment and vascularisation could be longitudinally examined in murine and human islet cells. Murine islet beta cell volume was unchanged over time. Transplanted embryonic pancreases increased to up to 6.1 times of their original volume and beta cell volume increased 90 times during 2 weeks. Conclusions/interpretation This method allows for repeated intravital imaging of grafts containing various sources of pancreatic tissue transplanted under the kidney capsule. Using fluorescent markers, dynamic information concerning engraftment or differentiation can be visualised and measured.
  • 111In-exendin imaging in patients with type 1 diabetes and healthy controls
    Item type: Other Conference Item
    Woliner-van der Weg, W.; Brom, M.; Béhe, M.; et al. (2014)
    Diabetologia
  • Antioxidants protect against diabetes by improving glucose homeostasis in mouse models of inducible insulin resistance and obesity
    Item type: Journal Article
    Straub, Leon G.; Efthymiou, Vissarion; Grandl, Gerald; et al. (2019)
    Diabetologia
    Aims/hypothesis In the context of diabetes, the health benefit of antioxidant treatment has been widely debated. In this study, we investigated the effect of antioxidant treatment during the development of insulin resistance and hyperphagia in obesity and partial lipodystrophy. Methods We studied the role of antioxidants in the regulation of insulin resistance using the tamoxifen-inducible fat-specific insulin receptor knockout (iFIRKO) mouse model, which allowed us to analyse the antioxidant’s effect in a time-resolved manner. In addition, leptin-deficient ob/ob mice were used as a hyperphagic, chronically obese and diabetic mouse model to validate the beneficial effect of antioxidants on metabolism. Results Acute induction of insulin receptor knockout in adipocytes changed the substrate preference to fat before induction of a diabetic phenotype including hyperinsulinaemia and hyperglycaemia. In healthy chow-fed animals as well as in morbidly obese mice, this diabetic phase could be reversed within a few weeks. Furthermore, after the induction of insulin receptor knockout in mature adipocytes, iFIRKO mice were protected from subsequent obesity development through high-fat diet feeding. By genetic tracing we show that the persistent fat mass loss in mice after insulin receptor knockout in adipocytes is not caused by the depletion of adipocytes. Treatment of iFIRKO mice with antioxidants postponed and reduced hyperglycaemia by increasing insulin sensitivity. In ob/ob mice, antioxidants rescued both hyperglycaemia and hyperphagia. Conclusions/interpretation We conclude that fat mass reduction through insulin resistance in adipocytes is not reversible. Furthermore, it seems unlikely that adipocytes undergo apoptosis during the process of extreme lipolysis, as a consequence of insulin resistance. Antioxidants have a beneficial health effect not only during the acute phase of diabetes development, but also in a temporary fashion once chronic obesity and diabetes have been established.
Publications 1 - 10 of 15