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Beta cell GABA secretion: route, physiological function, and potential for pharmacological modulation in diabetes therapy

Descripción del proyecto

¿Es el GABA un agente clave en el tratamiento de la diabetes?

El neurotransmisor ácido γ-aminobutírico (GABA) se produce y secreta en las células beta pancreáticas. Nuevas evidencias indican que el GABA puede retrasar o revertir la pérdida de células beta, lo que tiene importantes implicaciones para la diabetes. Los científicos del proyecto financiado con fondos europeos ISLET GABA se proponen comprender cómo se secreta el GABA en las células beta, así como descifrar su vía de transporte entre los islotes pancreáticos. La información sobre la señalización del GABA ayudará a identificar nuevas dianas terapéuticas para el tratamiento de la diabetes. Dado el incremento mundial de la prevalencia de la diabetes, los moduladores farmacológicos de la secreción de GABA podrían resultar ser revolucionarios para esta enfermedad y mejorar la calidad de vida de millones de personas.

Objetivo

According to the World Health Organisation, diabetes affects 422 million people worldwide, over 8% of the entire adult population. The progression of both type 1 and type 2 diabetes is characterised by a decrease in the number and function of beta-cells within pancreatic islets. It has recently been demonstrated that the neurotransmitter γ-aminobutyric acid (GABA), which is produced and secreted from beta cells, is able to slow and even reverse this loss of beta cell capacity. This finding has caused great excitement as treatments which directly address beta cell degeneration would revolutionise diabetes therapy. In order to realise this potential, it is essential that we understand the biogenesis, storage, and secretion of GABA in addition to its functional effects upon islet cells. I therefore propose to characterise a suggested route of GABA secretion from beta cells, assess its role in signalling between islet cells, and identify pharmacological modulators of GABA secretion. This study will be hosted by Patrik Rorsman (University of Gothenburg) with a secondment to AstraZeneca (Mölndal). This interdisciplinary study will combine my experience of applying cutting edge proteomics and genetic editing techniques to the study of protein trafficking with my host's world-leading expertise in islet cell physiology. Successful completion of the proposed work program will reveal fundamental details of islet GABA signalling and likely identify new therapeutic targets for the treatment of diabetes. Furthermore, during a cross-sectorial secondment to AstraZeneca I will carry out a high-throughput phenotypic screen to directly identify small molecule modulators of beta cell GABA secretion.

Coordinador

GOETEBORGS UNIVERSITET
Aportación neta de la UEn
€ 191 852,16
Dirección
VASAPARKEN
405 30 Goeteborg
Suecia

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Región
Södra Sverige Västsverige Västra Götalands län
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 191 852,16