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Modulation of glucose transporter protein by dietary flavonoids in type 2 diabetes mellitus.

Hajiaghaalipour F, Khalilpourfarshbafi M, Arya A - Int. J. Biol. Sci. (2015)

Bottom Line: Diabetes mellitus (DM) is a metabolic diseases characterized by hyperglycemia due to insufficient or inefficient insulin secretory response.This chronic disease is a global problem and there is a need for greater emphasis on therapeutic strategies in the health system.The antidiabetic potential of flavonoids are mainly through their modulatory effects on glucose transporter by enhancing GLUT-2 expression in pancreatic β cells and increasing expression and promoting translocation of GLUT-4 via PI3K/AKT, CAP/Cb1/TC10 and AMPK pathways.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;

ABSTRACT
Diabetes mellitus (DM) is a metabolic diseases characterized by hyperglycemia due to insufficient or inefficient insulin secretory response. This chronic disease is a global problem and there is a need for greater emphasis on therapeutic strategies in the health system. Phytochemicals such as flavonoids have recently attracted attention as source materials for the development of new antidiabetic drugs or alternative therapy for the management of diabetes and its related complications. The antidiabetic potential of flavonoids are mainly through their modulatory effects on glucose transporter by enhancing GLUT-2 expression in pancreatic β cells and increasing expression and promoting translocation of GLUT-4 via PI3K/AKT, CAP/Cb1/TC10 and AMPK pathways. This review highlights the recent findings on beneficial effects of flavonoids in the management of diabetes with particular emphasis on the investigations that explore the role of these compounds in modulating glucose transporter proteins at cellular and molecular level.

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Related in: MedlinePlus

GLUT-4 translocation takes place by IR-mediated phosphorylation of CAP, and formation of the CAP:Cbl:CrkII complex.
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Figure 4: GLUT-4 translocation takes place by IR-mediated phosphorylation of CAP, and formation of the CAP:Cbl:CrkII complex.

Mentions: Insulin-induced translocation of GLUT-4 in fat and muscle cells, takes place by two parallel signaling pathways namely, PI3K/AKT and CAP/Cb1/TC10 pathways as shown in figure 3 and figure 4, respectively. Activation of insulin receptor (IR), leads to phosphorylation of insulin receptor substrate (IRS), which in turn triggers the activation of phosphoinositide 3-kinase (PI3K). PI3k then phosphorylates the lipid phosphatidylinositol 4, 5-bisphosphate (PIP2) to yield phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 then activates phosphoinositide-dependent protein kinase 1 (PDK). PDK1-mediated phosphorylation of protein kinase B (Akt), in turn allows phosphorylation of the Rab GTPase-activating protein AS160 and leads to translocation of GLUT-4 from intracellular storage vesicles to plasma membrane and enhances the glucose uptake (Figure 3).


Modulation of glucose transporter protein by dietary flavonoids in type 2 diabetes mellitus.

Hajiaghaalipour F, Khalilpourfarshbafi M, Arya A - Int. J. Biol. Sci. (2015)

GLUT-4 translocation takes place by IR-mediated phosphorylation of CAP, and formation of the CAP:Cbl:CrkII complex.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4400383&req=5

Figure 4: GLUT-4 translocation takes place by IR-mediated phosphorylation of CAP, and formation of the CAP:Cbl:CrkII complex.
Mentions: Insulin-induced translocation of GLUT-4 in fat and muscle cells, takes place by two parallel signaling pathways namely, PI3K/AKT and CAP/Cb1/TC10 pathways as shown in figure 3 and figure 4, respectively. Activation of insulin receptor (IR), leads to phosphorylation of insulin receptor substrate (IRS), which in turn triggers the activation of phosphoinositide 3-kinase (PI3K). PI3k then phosphorylates the lipid phosphatidylinositol 4, 5-bisphosphate (PIP2) to yield phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 then activates phosphoinositide-dependent protein kinase 1 (PDK). PDK1-mediated phosphorylation of protein kinase B (Akt), in turn allows phosphorylation of the Rab GTPase-activating protein AS160 and leads to translocation of GLUT-4 from intracellular storage vesicles to plasma membrane and enhances the glucose uptake (Figure 3).

Bottom Line: Diabetes mellitus (DM) is a metabolic diseases characterized by hyperglycemia due to insufficient or inefficient insulin secretory response.This chronic disease is a global problem and there is a need for greater emphasis on therapeutic strategies in the health system.The antidiabetic potential of flavonoids are mainly through their modulatory effects on glucose transporter by enhancing GLUT-2 expression in pancreatic β cells and increasing expression and promoting translocation of GLUT-4 via PI3K/AKT, CAP/Cb1/TC10 and AMPK pathways.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;

ABSTRACT
Diabetes mellitus (DM) is a metabolic diseases characterized by hyperglycemia due to insufficient or inefficient insulin secretory response. This chronic disease is a global problem and there is a need for greater emphasis on therapeutic strategies in the health system. Phytochemicals such as flavonoids have recently attracted attention as source materials for the development of new antidiabetic drugs or alternative therapy for the management of diabetes and its related complications. The antidiabetic potential of flavonoids are mainly through their modulatory effects on glucose transporter by enhancing GLUT-2 expression in pancreatic β cells and increasing expression and promoting translocation of GLUT-4 via PI3K/AKT, CAP/Cb1/TC10 and AMPK pathways. This review highlights the recent findings on beneficial effects of flavonoids in the management of diabetes with particular emphasis on the investigations that explore the role of these compounds in modulating glucose transporter proteins at cellular and molecular level.

Show MeSH
Related in: MedlinePlus