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

 

Authors
Mu?oz Sandoval, Diana Carolina
Format
MasterThesis
Status
publishedVersion
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.

Publication Year
2015
Language
eng
Topic
BIOQU?MICA
BIOLOG?A MOLECULAR
TRANSPORTADORES DE GLUCOSE
SGLT2
DIABETES MELLITUS
GLUCOSA
Repository
Repositorio SENESCYT
Get full text
http://repositorio.educacionsuperior.gob.ec/handle/28000/2461
Rights
openAccess
License