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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

The insulin action can be inhibited by inflammatory signaling pathways. Inflammation and stressful stimuli activates c-jun amino terminal kinase (JNK), IκB kinase (IKK), and protein kinase Cθ (PKC-θ) which result in inhibition of insulin signaling. The activation of sterol regulatory element binding protein-1c (SREBP-1C), upstream stimulatory factor 1 (USF1), and liver X receptor (LXR)induces fatty acid synthesis.
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Figure 1: The insulin action can be inhibited by inflammatory signaling pathways. Inflammation and stressful stimuli activates c-jun amino terminal kinase (JNK), IκB kinase (IKK), and protein kinase Cθ (PKC-θ) which result in inhibition of insulin signaling. The activation of sterol regulatory element binding protein-1c (SREBP-1C), upstream stimulatory factor 1 (USF1), and liver X receptor (LXR)induces fatty acid synthesis.

Mentions: Inflammation and stressful stimuli activates protein kinase Cθ (PKC-θ) and IκB kinase (IKK) which results in inhibition of insulin signaling 21. These serine/threonine kinase, particularly IKK and c-jun amino terminal kinase (JNK), are also activated in obesity which highlights the overlap of metabolic and immune pathways 16-18. As shown in figure 1, IKK and JNK pathways are activated in response to stimuli during metabolic dysregulation including ligands for TNF-α, interleukin-1 (IL-1), Toll, or advanced glycation end products receptors (RAGE), intracellular stresses including reactive oxygen species (ROS) and ER stress, ceramide, and various PKC isoforms 22, 23. Upon activation of both JNK and IKK, IRS-1 phosphorylation takes place on Ser307 and Ser302 which results in impairment of insulin action 15, 16, 24-26. JNK and IKK pathways lead to the production of additional inflammatory mediators via transcriptional regulation of inflammatory genes by phosphorylating activator protein-1 (AP-1) and nuclear factor -kappa B (NF-κB), respectively 27. IKKβ activates NF-κB by phosphorylation of NF-κB inhibitor and consequently stimulates production of multiple inflammatory mediators, including TNF-α and IL-6 28.


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

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

The insulin action can be inhibited by inflammatory signaling pathways. Inflammation and stressful stimuli activates c-jun amino terminal kinase (JNK), IκB kinase (IKK), and protein kinase Cθ (PKC-θ) which result in inhibition of insulin signaling. The activation of sterol regulatory element binding protein-1c (SREBP-1C), upstream stimulatory factor 1 (USF1), and liver X receptor (LXR)induces fatty acid synthesis.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: The insulin action can be inhibited by inflammatory signaling pathways. Inflammation and stressful stimuli activates c-jun amino terminal kinase (JNK), IκB kinase (IKK), and protein kinase Cθ (PKC-θ) which result in inhibition of insulin signaling. The activation of sterol regulatory element binding protein-1c (SREBP-1C), upstream stimulatory factor 1 (USF1), and liver X receptor (LXR)induces fatty acid synthesis.
Mentions: Inflammation and stressful stimuli activates protein kinase Cθ (PKC-θ) and IκB kinase (IKK) which results in inhibition of insulin signaling 21. These serine/threonine kinase, particularly IKK and c-jun amino terminal kinase (JNK), are also activated in obesity which highlights the overlap of metabolic and immune pathways 16-18. As shown in figure 1, IKK and JNK pathways are activated in response to stimuli during metabolic dysregulation including ligands for TNF-α, interleukin-1 (IL-1), Toll, or advanced glycation end products receptors (RAGE), intracellular stresses including reactive oxygen species (ROS) and ER stress, ceramide, and various PKC isoforms 22, 23. Upon activation of both JNK and IKK, IRS-1 phosphorylation takes place on Ser307 and Ser302 which results in impairment of insulin action 15, 16, 24-26. JNK and IKK pathways lead to the production of additional inflammatory mediators via transcriptional regulation of inflammatory genes by phosphorylating activator protein-1 (AP-1) and nuclear factor -kappa B (NF-κB), respectively 27. IKKβ activates NF-κB by phosphorylation of NF-κB inhibitor and consequently stimulates production of multiple inflammatory mediators, including TNF-α and IL-6 28.

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