caa a22 4500 475771532 CHVBK 20180406123618.0 cr unu---uuuuu 170329e20000701xx s 000 0 eng 10.1007/s001250051467 doi (NATIONALLICENCE)springer-10.1007/s001250051467 Transgenic mice overexpressing α2A-adrenoceptors in pancreatic beta-cells show altered regulation of glucose homeostasis [Elektronische Daten] [J. C. Devedjian, A. Pujol, C. Cayla, M. George, A. Casellas, H. Paris, F. Bosch] Aims/hypothesis. To study the role of the human α2A-adrenoceptor in the regulation of insulin secretion and the maintenance of glucose homeostasis in transgenic mice overexpressing this receptor in pancreatic beta cells.¶Methods. A human insulin promoter/human α2C10-adrenoceptor chimeric gene was microinjected into mouse embryos and transgenic mice were obtained.¶Results. Analysis by RT-PCR showed that the expression of the transgene was restricted to pancreatic islets. Study of the binding of the α2-antagonist [3H]RX821 002 to membrane preparations showed that islets from transgenic mice had ninefold higher α2-adrenoceptor density than those from controls. Immunohistological analysis showed, however, no change in the number or size of islets between control and transgenic mice. Transgenic animals had normal glycaemia and insulinaemia in basal conditions but greater hyperglycaemic and hypoinsulinaemic responses after injection of the α2-agonist, UK14 304. The lower blood insulin concentration detected in transgenic mice was a reflection of a stronger inhibitory effect of the α2-agonist on glucose-stimulated insulin secretion in transgenic islets than in controls. Furthermore, transgenic mice did not have lower glycaemia to basal values after an intraperitoneal glucose tolerance test. This defect was abolished by treatment with the α2-adrenoceptor antagonist, RX821 002.¶Conclusion/interpretation. These results provide evidence in vivo that overexpression of α2-adrenoceptors in beta cells can lead to impaired insulin secretion and glucose intolerance. [Diabetologia (2000) 43: 899-906] Springer-Verlag Berlin Heidelberg, 2000 Keywords Diabetes, insulin, catecholamines, α2-agonist, adrenoceptor, islets, transgenic mice nationallicence Devedjian J. C. Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Bellaterra, Spain, ES aut Pujol A. Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Bellaterra, Spain, ES aut Cayla C. INSERM U388, Louis Bugnard Institute, Toulouse, France, FR aut George M. Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Bellaterra, Spain, ES aut Casellas A. Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Bellaterra, Spain, ES aut Paris H. INSERM U388, Louis Bugnard Institute, Toulouse, France, FR aut Bosch F. Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Bellaterra, Spain, ES aut https://doi.org/10.1007/s001250051467 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051467 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Devedjian J. C. Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Bellaterra, Spain, ES aut NATIONALLICENCE 700 1- Pujol A. Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Bellaterra, Spain, ES aut NATIONALLICENCE 700 1- Cayla C. INSERM U388, Louis Bugnard Institute, Toulouse, France, FR aut NATIONALLICENCE 700 1- George M. Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Bellaterra, Spain, ES aut NATIONALLICENCE 700 1- Casellas A. Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Bellaterra, Spain, ES aut NATIONALLICENCE 700 1- Paris H. INSERM U388, Louis Bugnard Institute, Toulouse, France, FR aut NATIONALLICENCE 700 1- Bosch F. Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Bellaterra, Spain, ES aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer