Limits...
Certain Diet and Lifestyle May Contribute to Islet β-cells Protection in Type-2 Diabetes via the Modulation of Cellular PI3K/AKT Pathway.

Kitagishi Y, Nakanishi A, Minami A, Asai Y, Yasui M, Iwaizako A, Suzuki M, Ono Y, Ogura Y, Matsuda S - Open Biochem J (2014)

Bottom Line: Understanding the regulations of this pathway may provide a better efficacy of new therapeutic approaches.In this review, we summarize advances on the involvement of the PI3K/AKT pathway in hypothetical intra-cellular signaling of islet β-cells.The molecular mechanisms contributing to the disease are the subject of considerable investigation, as a better understanding of the pathogenesis will lead to novel therapies against a condition of the disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan.

ABSTRACT
PI3K/AKT pathway has been shown to play a pivotal role on islet β-cell protection, enhancing β-cell survival by stimulating cell proliferation and inhibiting cell apoptosis. Accordingly, this pathway appears to be crucial in type-2 diabetes. Understanding the regulations of this pathway may provide a better efficacy of new therapeutic approaches. In this review, we summarize advances on the involvement of the PI3K/AKT pathway in hypothetical intra-cellular signaling of islet β-cells. As recent findings may show the nutritional regulation of the survival pathway in the islet β-cells through activation of the PI3K/AKT pathway, we also review studies on the features of several diets, correlated lifestyle, and its signaling pathway involved in type-2 diabetes. The molecular mechanisms contributing to the disease are the subject of considerable investigation, as a better understanding of the pathogenesis will lead to novel therapies against a condition of the disease.

No MeSH data available.


Related in: MedlinePlus

Several modulators linked to the PI3K/AKT/PTEN pathway are demonstrated, whose potential molecular targets may be based on the predominant sites. Arrowhead means stimulation whereas hammerhead represents inhibition, suggesting implication of PI3K/AKT/ PTEN modulators for the therapy of diabetes via the pancreatic β-cells protection. Note that some critical events have been omitted for clarity.SSRI: Selective Serotonin Reuptake Inhibitors MAOi: Monoamine oxidase inhibitors 5-HT: 5-hydroxytryptamine, serotonin
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4231374&req=5

Figure 2: Several modulators linked to the PI3K/AKT/PTEN pathway are demonstrated, whose potential molecular targets may be based on the predominant sites. Arrowhead means stimulation whereas hammerhead represents inhibition, suggesting implication of PI3K/AKT/ PTEN modulators for the therapy of diabetes via the pancreatic β-cells protection. Note that some critical events have been omitted for clarity.SSRI: Selective Serotonin Reuptake Inhibitors MAOi: Monoamine oxidase inhibitors 5-HT: 5-hydroxytryptamine, serotonin

Mentions: Studies have indicated that serotonin exerts part of their actions by modulating the activity of PI3K/AKT pathway [69]. Through the G-protein coupled receptors, serotonin activates the PI3K/AKT/mTOR/p70S6K signaling (Fig. 2), and this activation is similar to that seen in VEGF signaling [70]. One of the major functions of the PI3K/AKT pathway is to promote growth factor-mediated cell survival and to block cell apoptosis. GSK3β has a role for the regulation of serotonin receptor in cell surface trafficking [71]. Antidepressants acting on serotonin neurotransmission activate AKT and inhibit GSK3β. Lithium also activates PI3K/AKT signaling. In addition, drugs like SSRIs and MAO inhibitors that elevate serotonin synaptic transmission have been shown to inhibit GSK3β [72]. The mood stabilizers such as valproate also inhibit GSK3β [73]. Defective central AKT function alters serotonin signaling as well as serotonin associated behaviors, demonstrating a novel role for PI3K/AKT pathway in maintaining serotonin receptor function [74]. It is plausible that PI3K/AKT/GSK3β pathway also functions downstream the serotonin receptor in pancreatic islet β-cells.


Certain Diet and Lifestyle May Contribute to Islet β-cells Protection in Type-2 Diabetes via the Modulation of Cellular PI3K/AKT Pathway.

Kitagishi Y, Nakanishi A, Minami A, Asai Y, Yasui M, Iwaizako A, Suzuki M, Ono Y, Ogura Y, Matsuda S - Open Biochem J (2014)

Several modulators linked to the PI3K/AKT/PTEN pathway are demonstrated, whose potential molecular targets may be based on the predominant sites. Arrowhead means stimulation whereas hammerhead represents inhibition, suggesting implication of PI3K/AKT/ PTEN modulators for the therapy of diabetes via the pancreatic β-cells protection. Note that some critical events have been omitted for clarity.SSRI: Selective Serotonin Reuptake Inhibitors MAOi: Monoamine oxidase inhibitors 5-HT: 5-hydroxytryptamine, serotonin
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231374&req=5

Figure 2: Several modulators linked to the PI3K/AKT/PTEN pathway are demonstrated, whose potential molecular targets may be based on the predominant sites. Arrowhead means stimulation whereas hammerhead represents inhibition, suggesting implication of PI3K/AKT/ PTEN modulators for the therapy of diabetes via the pancreatic β-cells protection. Note that some critical events have been omitted for clarity.SSRI: Selective Serotonin Reuptake Inhibitors MAOi: Monoamine oxidase inhibitors 5-HT: 5-hydroxytryptamine, serotonin
Mentions: Studies have indicated that serotonin exerts part of their actions by modulating the activity of PI3K/AKT pathway [69]. Through the G-protein coupled receptors, serotonin activates the PI3K/AKT/mTOR/p70S6K signaling (Fig. 2), and this activation is similar to that seen in VEGF signaling [70]. One of the major functions of the PI3K/AKT pathway is to promote growth factor-mediated cell survival and to block cell apoptosis. GSK3β has a role for the regulation of serotonin receptor in cell surface trafficking [71]. Antidepressants acting on serotonin neurotransmission activate AKT and inhibit GSK3β. Lithium also activates PI3K/AKT signaling. In addition, drugs like SSRIs and MAO inhibitors that elevate serotonin synaptic transmission have been shown to inhibit GSK3β [72]. The mood stabilizers such as valproate also inhibit GSK3β [73]. Defective central AKT function alters serotonin signaling as well as serotonin associated behaviors, demonstrating a novel role for PI3K/AKT pathway in maintaining serotonin receptor function [74]. It is plausible that PI3K/AKT/GSK3β pathway also functions downstream the serotonin receptor in pancreatic islet β-cells.

Bottom Line: Understanding the regulations of this pathway may provide a better efficacy of new therapeutic approaches.In this review, we summarize advances on the involvement of the PI3K/AKT pathway in hypothetical intra-cellular signaling of islet β-cells.The molecular mechanisms contributing to the disease are the subject of considerable investigation, as a better understanding of the pathogenesis will lead to novel therapies against a condition of the disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan.

ABSTRACT
PI3K/AKT pathway has been shown to play a pivotal role on islet β-cell protection, enhancing β-cell survival by stimulating cell proliferation and inhibiting cell apoptosis. Accordingly, this pathway appears to be crucial in type-2 diabetes. Understanding the regulations of this pathway may provide a better efficacy of new therapeutic approaches. In this review, we summarize advances on the involvement of the PI3K/AKT pathway in hypothetical intra-cellular signaling of islet β-cells. As recent findings may show the nutritional regulation of the survival pathway in the islet β-cells through activation of the PI3K/AKT pathway, we also review studies on the features of several diets, correlated lifestyle, and its signaling pathway involved in type-2 diabetes. The molecular mechanisms contributing to the disease are the subject of considerable investigation, as a better understanding of the pathogenesis will lead to novel therapies against a condition of the disease.

No MeSH data available.


Related in: MedlinePlus