Category

Oral - Applied

Description

Type-two diabetes (T2D) results from insulin resistance causing persistent high blood glucose levels, despite a normal production of insulin. While studying the impact of various coffee polyphenol derivatives, we discovered that enterolactone (ENL) induces glucose uptake in differentiated adipocytes. Insulin-dependent glucose uptake occurs in various cell types, but primarily in adipose and muscle cells. This study focuses on adipose cells, specifically characterizing the mechanism of ENL induced glucose uptake. The goal of our study is to characterize the molecular mechanism of ENL to promote glucose uptake in 3T3-L1 differentiated adipocytes. 3T3-L1 differentiated adipocytes were treated with Enterolactone in a concentration-dependent manner to determine its effect on glucose uptake. To ascertain the cellular route of glucose uptake, specific known glucose transporter 4 (GLUT4) inhibitors were used (BAY-876 and Ritonovir). GLUT4 is a plasma membrane protein responsible for transporting glucose into the cell. To assess a portion of the intracellular mechanism of ENL Akt phosphorylation was tested. Akt phosphorylation serves as an intracellular mediator for bringing GLUT4 to the plasma membrane. The differentiated adipocytes, when treated with ENL, showed a significant increase in glucose uptake compared to the negative control. Treatment of adipocytes with ENL and BAY-876 (290nM) and with ENL and Ritonavir showed a significant decrease in glucose uptake. ENL treatments also showed a significant increase in Akt-phosphorylation. The results support that ENL induces glucose uptake in adipocytes and does so in a GLUT4 and Akt-phosphorylation dependent manner. This study provides data to support the hypothesis that ENL may be a useful treatment to provide an alternative method for maintaining proper blood glucose levels in individuals with T2D. Future research will seek to elucidate more of the intracellular mechanism of ENL to determine if it is a viable compound to be tested in an in-vivo model of T2D.

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Doctorate - 1st Place Award Winner

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Apr 16th, 10:00 AM

Enterolactone as a Potential Therapeutic Agent for Treatment of Type-two Diabetes

Oral - Applied

Type-two diabetes (T2D) results from insulin resistance causing persistent high blood glucose levels, despite a normal production of insulin. While studying the impact of various coffee polyphenol derivatives, we discovered that enterolactone (ENL) induces glucose uptake in differentiated adipocytes. Insulin-dependent glucose uptake occurs in various cell types, but primarily in adipose and muscle cells. This study focuses on adipose cells, specifically characterizing the mechanism of ENL induced glucose uptake. The goal of our study is to characterize the molecular mechanism of ENL to promote glucose uptake in 3T3-L1 differentiated adipocytes. 3T3-L1 differentiated adipocytes were treated with Enterolactone in a concentration-dependent manner to determine its effect on glucose uptake. To ascertain the cellular route of glucose uptake, specific known glucose transporter 4 (GLUT4) inhibitors were used (BAY-876 and Ritonovir). GLUT4 is a plasma membrane protein responsible for transporting glucose into the cell. To assess a portion of the intracellular mechanism of ENL Akt phosphorylation was tested. Akt phosphorylation serves as an intracellular mediator for bringing GLUT4 to the plasma membrane. The differentiated adipocytes, when treated with ENL, showed a significant increase in glucose uptake compared to the negative control. Treatment of adipocytes with ENL and BAY-876 (290nM) and with ENL and Ritonavir showed a significant decrease in glucose uptake. ENL treatments also showed a significant increase in Akt-phosphorylation. The results support that ENL induces glucose uptake in adipocytes and does so in a GLUT4 and Akt-phosphorylation dependent manner. This study provides data to support the hypothesis that ENL may be a useful treatment to provide an alternative method for maintaining proper blood glucose levels in individuals with T2D. Future research will seek to elucidate more of the intracellular mechanism of ENL to determine if it is a viable compound to be tested in an in-vivo model of T2D.

 

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