Imagen de Portada

Phytochemical inhibition of intestinal and kidney glucose transporters expressed in the Xenopus laevis oocyte system

Diabetes mellitus type 2 involves several pathological complications due to hyperglycaemia, which is the increase of glucose levels in blood. This can lead to severe outcomes as blindness and nephropathy. Glucose transporters represent an important target for the treatment of Diabetes mellitus type...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autor Principal: Mu?oz Sandoval, Diana Carolina
Otros Autores: Corpe, Christopher
Formato: Tesis de Maestría
Lenguaje:eng
Publicado: Londres / King's College London 2016
Materias:
BIOQU?MICA
BIOLOG?A MOLECULAR
TRANSPORTADORES DE GLUCOSE
SGLT2
DIABETES MELLITUS
GLUCOSA
Acceso en línea:http://repositorio.educacionsuperior.gob.ec/handle/28000/2461
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:localhost:28000-2461
recordtype dspace
spelling oai:localhost:28000-24612017-02-20T17:38:25Z Phytochemical inhibition of intestinal and kidney glucose transporters expressed in the Xenopus laevis oocyte system Mu?oz Sandoval, Diana Carolina Corpe, Christopher Sturzenbaum, Stephen BIOQU?MICA BIOLOG?A MOLECULAR TRANSPORTADORES DE GLUCOSE SGLT2 DIABETES MELLITUS GLUCOSA Diabetes mellitus type 2 involves several pathological complications due to hyperglycaemia, which is the increase of glucose levels in blood. This can lead to severe outcomes as blindness and nephropathy. Glucose transporters represent an important target for the treatment of Diabetes mellitus type 2 and its prevention through the control of post-prandial glucose levels. Drugs to delay the absorption of glucose in the gut (?-glucosidases) and more recently, drugs that inhibit glucose reabsorption in the kidney mediated by SGLT2 (flozins) are available in the market. However, inhibition studies targeting SGLT2, which is responsible for 97% of the glucose reabsorption, do not reach a complete reabsorption inhibition in the kidney. A splice variant of human SGLT2 was identified and its expression in the kidney was confirmed in this study. A characterization of this human SGLT2 splice variant in Xenopus oocyte system was carried out as a possible reabsorption mechanism insensitive to this inhibition, which could clarify this reabsorption paradox. However, preliminary results obtained were not conclusive, hence further analysis of this variant cleaved the UTR sequence could be a plausible approach to follow. SGLT1 as the main glucose transporter in the gut was studied as target for phytochemical inhibition. Studies carried out in the Xenopus oocyte system showed that extracts from OptiBerry?, blackcurrant and apple significantly inhibit SGLT1 transport. Dose response assays carried out with blackcurrant extract obtained an IC 50 of 0.129 mg of total phenolic compounds/mL. Apple extract dose response assays should be further studied with a change of concentration range or fractioning of the extract. This study showed that phytochemical inhibition of sugar transporters can be achieved by different fruit extracts and more research should be conducted in this field to identify compounds that can be used in treatments to regulate hyperglycaemia. 2016-10-12T16:25:26Z 2016-10-12T16:25:26Z 2015-12 masterThesis Mu?oz Sandoval, Diana Carolina. (2015). Phytochemical inhibition of intestinal and kidney glucose transporters expressed in the Xenopus laevis oocyte system. (Trabajo de titulaci?n de M?ster en Investigaci?n de Ciencias Biom?dicas y Moleculares). King's College London. Londres. 95 p. http://repositorio.educacionsuperior.gob.ec/handle/28000/2461 eng 95 p. Londres / King's College London
institution SENESCYT
collection Repositorio SENESCYT
biblioteca Biblioteca Senescyt
language eng
format Tesis de Maestría
topic BIOQU?MICA
BIOLOG?A MOLECULAR
TRANSPORTADORES DE GLUCOSE
SGLT2
DIABETES MELLITUS
GLUCOSA
spellingShingle BIOQU?MICA
BIOLOG?A MOLECULAR
TRANSPORTADORES DE GLUCOSE
SGLT2
DIABETES MELLITUS
GLUCOSA
Mu?oz Sandoval, Diana Carolina
Phytochemical inhibition of intestinal and kidney glucose transporters expressed in the Xenopus laevis oocyte system
description Diabetes mellitus type 2 involves several pathological complications due to hyperglycaemia, which is the increase of glucose levels in blood. This can lead to severe outcomes as blindness and nephropathy. Glucose transporters represent an important target for the treatment of Diabetes mellitus type 2 and its prevention through the control of post-prandial glucose levels. Drugs to delay the absorption of glucose in the gut (?-glucosidases) and more recently, drugs that inhibit glucose reabsorption in the kidney mediated by SGLT2 (flozins) are available in the market. However, inhibition studies targeting SGLT2, which is responsible for 97% of the glucose reabsorption, do not reach a complete reabsorption inhibition in the kidney. A splice variant of human SGLT2 was identified and its expression in the kidney was confirmed in this study. A characterization of this human SGLT2 splice variant in Xenopus oocyte system was carried out as a possible reabsorption mechanism insensitive to this inhibition, which could clarify this reabsorption paradox. However, preliminary results obtained were not conclusive, hence further analysis of this variant cleaved the UTR sequence could be a plausible approach to follow. SGLT1 as the main glucose transporter in the gut was studied as target for phytochemical inhibition. Studies carried out in the Xenopus oocyte system showed that extracts from OptiBerry?, blackcurrant and apple significantly inhibit SGLT1 transport. Dose response assays carried out with blackcurrant extract obtained an IC 50 of 0.129 mg of total phenolic compounds/mL. Apple extract dose response assays should be further studied with a change of concentration range or fractioning of the extract. This study showed that phytochemical inhibition of sugar transporters can be achieved by different fruit extracts and more research should be conducted in this field to identify compounds that can be used in treatments to regulate hyperglycaemia.
author2 Corpe, Christopher
author_facet Corpe, Christopher
Mu?oz Sandoval, Diana Carolina
author Mu?oz Sandoval, Diana Carolina
author_sort Mu?oz Sandoval, Diana Carolina
title Phytochemical inhibition of intestinal and kidney glucose transporters expressed in the Xenopus laevis oocyte system
title_short Phytochemical inhibition of intestinal and kidney glucose transporters expressed in the Xenopus laevis oocyte system
title_full Phytochemical inhibition of intestinal and kidney glucose transporters expressed in the Xenopus laevis oocyte system
title_fullStr Phytochemical inhibition of intestinal and kidney glucose transporters expressed in the Xenopus laevis oocyte system
title_full_unstemmed Phytochemical inhibition of intestinal and kidney glucose transporters expressed in the Xenopus laevis oocyte system
title_sort phytochemical inhibition of intestinal and kidney glucose transporters expressed in the xenopus laevis oocyte system
publisher Londres / King's College London
publishDate 2016
url http://repositorio.educacionsuperior.gob.ec/handle/28000/2461
_version_ 1634995145700016128
score 11,871979

Ejemplares similares