Artikel
Roux-en-Y gastric bypass induced alteration of the entero-insulinar axis in Zucker (fa/fa) rats – Relevant impact on glucose tolerance?
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Autoren
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Florian Seyfried
- Universitätsklinikum Würzburg, Klinik und Poliklinik für Allgemein-,Viszeral-, Gefäß- und Kinderchirurgie, Würzburg
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Arno Nordbeck
- Universitätsklinikum Würzburg, Klinik und Poliklinik für Allgemein-,Viszeral-, Gefäß- und Kinderchirurgie, Würzburg
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Laura Rotzinger
- Universitätsklinikum Würzburg, Klinik und Poliklinik für Allgemein-,Viszeral-, Gefäß- und Kinderchirurgie, Würzburg
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Christoph-Thomas Germer
- Universitätsklinikum Würzburg, Klinik und Poliklinik für Allgemein-,Viszeral-, Gefäß- und Kinderchirurgie, Würzburg
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Marco Büter
- UniversitätsSpital Zürich, Klinik für Viszeral- und Transplantationschirurgie, Zürich
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Christian Jurowich
- Universitätsklinikum Würzburg, Klinik und Poliklinik für Allgemein-,Viszeral-, Gefäß- und Kinderchirurgie, Würzburg
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Christoph Otto
- Universitätsklinikum Würzburg, Klinik und Poliklinik für Allgemein-,Viszeral-, Gefäß- und Kinderchirurgie, Würzburg
| Veröffentlicht: | 21. März 2014 |
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Gliederung
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Introduction: Caloric restriction and body weight loss are key factors to improve insulin resistance in patients with type 2 diabetes associated with obesity. Bariatric surgery and, especially, intestinal bypass procedures have been shown to cause weight loss independent effects on glucose control in particular by altering the entero-insulinar axis. There is limited data on the effect size of this body weight loss independent effect on glucose control.
Material and methods: Male Zucker (fa/fa) rats, aged 12 weeks, were randomized to either Roux-en-Y gastric bypass (RYGB, n=7) or sham surgery (sham, n=7). Postoperatively sham- operated and RYGB rats received ad libitum normal chow. Seven body weight matched (BWM) rats to RYGB served as additional controls. Body weight and food intake were monitored daily. Four weeks after surgery an oral glucose tolerance test (OGTT) was performed and levels of glucose, insulin and Glucagon-like Peptide-1 (GLP-1) were measured and HOMA-IR calculated. Immune histological findings (Insulin) of the pancreas islets were analysed and GLP-1 receptor and PDX-1 mRNA content quantified.
Results: Ad libitum fed sham rats consumed more food (p<0.001) and gained more weight (p<0.001) compared to both RYGB and BWM controls. During the OGTT impaired glucose tolerance was evident only in shams (p<0.01), but not in RYGB and BWM controls. After the glucose load RYGB rats responded with > 2.5-fold increase of GLP-1 (p<0.01) and insulin (p<0.01) levels compared to both shams and BWM controls. Histology revealed hyperplasia and sings of degeneration in shams and BWM controls, but not in RYGB. PDX-1 mRNA content was lower (p<0.05) and GLP-1 receptor mRNA content higher after RYGB compared to shams and BWM controls (p<0.05).
Conclusion: In this animal model, caloric restriction and body weight loss, but not RYGB specific effects, appear to be predominant in improving glucose tolerance. However, only RYGB caused significant changes in the entero-insulinar axis including an exaggerated rise in GLP-1 and insulin, as well as histological findings consistent with β-cell protective effects.
