رسالة جامعية
Autocrine/paracrine interactions moendocrine pancreasdulating hormone release in the endocrine pancreas
| العنوان: | Autocrine/paracrine interactions moendocrine pancreasdulating hormone release in the endocrine pancreas |
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| المؤلفون: | Cabrera, Over |
| بيانات النشر: | Institutionen för molekylär medicin och kirurgi / Department of Molecular Medicine and Surgery |
| سنة النشر: | 2007 |
| المجموعة: | Karolinska Institutet: Publications |
| الوصف: | Human islet transplantation is emerging as an alternative to pancreas transplantation or insulin therapy in the treatment of type I diabetes. It has been possible to achieve euglycemia by transplanting isolated human islets in patients who suffer from the long term side effects of diabetes and insulin therapy. However, the islet transplantation procedure is still experimental. To obtain FDA approval, each batch of islets will have to be labeled with its potency to meet the transplantation criteria. Consequently, finding an in vitro test that predicts the quality of the islets prior to transplantation will require a better understanding of the human islet physiology. In this thesis we report on the generation of an in vitro perifusion machine with high throughput capabilities which integrates with other commercial high content screening systems. These technologies were successfully applied to measure [Ca2+]i and hormone release from batches of damaged islets with decreased viability, and it was possible to differentiate those islets from their undamaged counterparts. Pharmacological profiling of individual batches of islet cells proved feasible, measuring both [Ca2+]i and hormone release. Moreover, we showed that the hormone release assay can be used to distinguish batches of human islets from healthy donors and donors with type II diabetes. Our data on human islets revealed a cytoarchitecture that differs from that of other animal models used to study islet physiology and diabetes. In the human islet, all endocrine cells are intermingled throughout the islets without the mantle-core segregation observed in the rodent islet. The endocrine cells are facing blood vessels and they appear without a specific pattern. Additionally, [Ca2+]i handling in human islets is different from that in mouse islets. While the entire human islet does not show oscillations in [Ca2+]i as described for the mouse islet, single human beta cells show oscillations in [Ca2+]i that resemble those found in mouse. Our data showed that ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| وصف الملف: | application/pdf |
| اللغة: | English |
| ردمك: | 978-91-7357-378-8 91-7357-378-7 |
| العلاقة: | I. Cabrera O, Jacques-Silva MC, Berman DM, Fachado A, Echeverri F, Poo RE, Khan A, Kenyon NS, Ricordi C, Berggren PO, Caicedo A (2007). Automated, high-throughput assays for evaluation of human pancreatic islet cell function. [Accepted] ::doi::10.3727/000000007783472408 ::pmid::18351020 ::isi::000253364200008; II. Cabrera O, Berman DM, Kenyon NS, Ricordi C, Berggren PO, Caicedo A (2006). The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc Natl Acad Sci USA. 103(7): 2334-9. ::doi::10.1073/pnas.0510790103 ::pmid::16461897 ::isi::000235411600060; III. Cabrera O, Jacques-Silva MC, Köhler M, Berman DM, Kenyon NS, Ricordi C, Caicedo A, Berggren PO (2007). Glutamate is an autocrine signal essential for glucagon release. [Submitted]; IV. Jacques-Silva MC, Cabrera O, Makeeva N, Berman D, Kenyon NS, Ricordi C, Pileggi A, Molano D, Berggren PO, Caicedo A (2007). ATP is a positive autocrine signal in the human pancreatic beta cell. [Submitted]; 20071128cabr; http://hdl.handle.net/10616/38339Test |
| الإتاحة: | http://hdl.handle.net/10616/38339Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.D09721BB |
| قاعدة البيانات: | BASE |
| ردمك: | 9789173573788 9173573787 |
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