Abstract
Considering that obesity and diabetes are some of the most important health problems in the world today, a lot studies have investigated the powerful effects of bariatric surgery on weight loss and diabetes remission during the past decade. An increased release of gut hormones is believed to contribute to the positive effects of bariatic surgery but the mechanisms remain largely unknown. The endocrine cells of the gastrointestinal tract that produce and secrete hormones are difficult to examine as they are distributed as single cells. Several types of endocrine cells together produce more than 40 hormones. In this PhD study, gut morphology and the population of endocrine cells have been examined in three rodent animal models using stereological techniques.
First, in a rodent model of type-2 diabetes (T2DM), the Zucker diabetic fatty rat (ZDF), the population of endocrine L-cells and the gut morphology were quantified. The number of Lcells was 4.8 million in the normal rat and the L-cells were found to double in number in the diabetic ZDF rat model.
Second, the L-cell population, gut morphology and endocrine cell gene expression were examined in a rodent model of Roux-en-Y gastric bypass (RYGB). In all regions of the gastrointestinal tract the mucosa showed extensive proliferation. The number of L-cells was increased to more than double and the L-cells in the common channel showed increased expression of mRNA coding for L-cell hormones, suggesting increased activity of these cells.
Finally, we investigated several endocrine subtypes, including the L-cell, together with gut morphology in a rodent model of Ileal Transposition (IT) 1.5 month post-surgery. In this study a 60% increase in the number of endocrine cells was found, and all four subtypes (neurotensin-, GLP-1-, cholecystokinin- and serotonin-producing cells) of endocrine cells investigated were found to be upregulated.
These studies contribute to the understanding of the anatomical distribution of the endocrine L-cells. The investigations show a high plasticity of the gut endocrine cell density and distribution in response to surgical interventions. The increase in the number of endocrine cells is probably a mechanism involved in the enhanced blood levels of gut hormones following bariatric surgery.
First, in a rodent model of type-2 diabetes (T2DM), the Zucker diabetic fatty rat (ZDF), the population of endocrine L-cells and the gut morphology were quantified. The number of Lcells was 4.8 million in the normal rat and the L-cells were found to double in number in the diabetic ZDF rat model.
Second, the L-cell population, gut morphology and endocrine cell gene expression were examined in a rodent model of Roux-en-Y gastric bypass (RYGB). In all regions of the gastrointestinal tract the mucosa showed extensive proliferation. The number of L-cells was increased to more than double and the L-cells in the common channel showed increased expression of mRNA coding for L-cell hormones, suggesting increased activity of these cells.
Finally, we investigated several endocrine subtypes, including the L-cell, together with gut morphology in a rodent model of Ileal Transposition (IT) 1.5 month post-surgery. In this study a 60% increase in the number of endocrine cells was found, and all four subtypes (neurotensin-, GLP-1-, cholecystokinin- and serotonin-producing cells) of endocrine cells investigated were found to be upregulated.
These studies contribute to the understanding of the anatomical distribution of the endocrine L-cells. The investigations show a high plasticity of the gut endocrine cell density and distribution in response to surgical interventions. The increase in the number of endocrine cells is probably a mechanism involved in the enhanced blood levels of gut hormones following bariatric surgery.
| Originalsprog | Engelsk |
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| Forlag | Department of Nutrition, Exercise and Sports, Faculty of Sciences, University of Copenhagen |
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| Antal sider | 118 |
| ISBN (Trykt) | i |
| Status | Udgivet - 2013 |