15906
2017
eng
16795
7
article
1
2018-03-16
--
--
Whitening and impaired glucose utilization of brown adipose tissue in a rat model of type 2 diabetes mellitus
Brown adipose tissue (BAT) is an attractive therapeutic target to combat diabetes and obesity due to its ability to increase glucose expenditure. In a genetic rat model (ZDF fa/fa) of type-2 diabetes and obesity, we aimed to investigate glucose utilization of BAT by \(^{18}\)F-FDG PET imaging. Male Zucker diabetic fatty (ZDF) and Male Zucker lean (ZL) control rats were studied at 13 weeks. Three weeks prior to imaging, ZDF rats were randomized into a no-restriction (ZDF-ND) and a mild calorie restriction (ZDF-CR) group. Dynamic \(^{18}\)F-FDG PET using a dedicated small animal PET system was performed under hyperinsulinemic-euglycemic clamp. \(^{18}\)F-FDG PET identified intense inter-scapular BAT glucose uptake in all ZL control rats, while no focally increased \(^{18}\)F-FDG uptake was detected in all ZDF-ND rats. Mild but significant improved BAT tracer uptake was identified after calorie restriction in diabetic rats (ZDF-CR). The weight of BAT tissue and fat deposits were significantly increased in ZDF-CR and ZDF-ND rats as compared to ZL controls, while UCP-1 and mitochondrial concentrations were significantly decreased. Whitening and severely impaired insulin-stimulated glucose uptake in BAT was confirmed in a rat model of type-2 diabetes. Additionally, calorie restriction partially restored the impaired BAT glucose uptake.
Scientific Reports
10.1038/s41598-017-17148-w
urn:nbn:de:bvb:20-opus-159066
Scientific Reports 7:16795 (2017). DOI: 10.1038/s41598-017-17148-w
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Constantin Lapa
Paula Arias-Loza
Nobuyuki Hayakawa
Hiroshi Wakabayashi
Rudolf A. Werner
Xinyu Chen
Tetsuya Shinaji
Ken Herrmann
Theo Pelzer
Takahiro Higuchi
eng
uncontrolled
molecular medicine
eng
uncontrolled
endocrinology
Krankheiten
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik I
Förderzeitraum 2017
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/15906/Lapa_Scientific_Reports.pdf
17176
2018
eng
17631
8
article
1
2018-11-13
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Left Ventricular Diastolic Dysfunction in a Rat Model of Diabetic Cardiomyopathy using ECG-gated \(^{18}\)F-FDG PET
In diabetic cardiomyopathy, left ventricular (LV) diastolic dysfunction is one of the earliest signs of cardiac involvement prior to the definitive development of heart failure (HF). We aimed to explore the LV diastolic function using electrocardiography (ECG)-gated \(^{18}\)F-fluorodeoxyglucose positron emission tomography (\(^{18}\)F-FDG PET) imaging beyond the assessment of cardiac glucose utilization in a diabetic rat model. ECG-gated \(^{18}\)F-FDG PET imaging was performed in a rat model of type 2 diabetes (ZDF fa/fa) and ZL control rats at age of 13 weeks (n=6, respectively). Under hyperinsulinemic-euglycemic clamp to enhance cardiac activity, \(^{18}\)F-FDG was administered and subsequently, list-mode imaging using a dedicated small animal PET system with ECG signal recording was performed. List-mode data were sorted and reconstructed into tomographic images of 16 frames per cardiac cycle. Left ventricular functional parameters (systolic: LV ejection fraction (EF), heart rate (HR) vs. diastolic: peak filling rate (PFR)) were obtained using an automatic ventricular edge detection software. No significant difference in systolic function could be obtained (ZL controls vs. ZDF rats: LVEF, 62.5±4.2 vs. 59.4±4.5%; HR: 331±35 vs. 309±24 bpm; n.s., respectively). On the contrary, ECG-gated PET imaging showed a mild but significant decrease of PFR in the diabetic rats (ZL controls vs. ZDF rats: 12.1±0.8 vs. 10.2±1 Enddiastolic Volume/sec, P<0.01). Investigating a diabetic rat model, ECG-gated \(^{18}\)F-FDG PET imaging detected LV diastolic dysfunction while systolic function was still preserved. This might open avenues for an early detection of HF onset in high-risk type 2 diabetes before cardiac symptoms become apparent.
Scientific Reports
10.1038/s41598-018-35986-0
urn:nbn:de:bvb:20-opus-171765
Scientific Reports 8:17631 (2018). DOI: 10.1038/s41598-018-35986-0
701983
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Christoph Eissler
Nobuyuki Hayakawa
Paula Arias-Loza
Hiroshi Wakabayashi
Mehrbod S. Javadi
Xinyu Chen
Tetsuya Shinaji
Constantin Lapa
Theo Pelzer
Takahiro Higuchi
eng
uncontrolled
diabetic cardiomyopathy
eng
uncontrolled
personalized treatment
eng
uncontrolled
precision medicine
eng
uncontrolled
ZDF rats
eng
uncontrolled
ECG
eng
uncontrolled
PET
eng
uncontrolled
\(^{18}\)F-fluorodeoxyglucose
eng
uncontrolled
\(^{18}\)F-FDG
eng
uncontrolled
diabetes
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik I
OpenAIRE
Förderzeitraum 2018
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17176/Werner_Scientific_Reports.pdf