Cover Story Current Issue

In 1975, Arion and colleagues discovered that hepatocytes release glucose into the bloodstream in response to hypoglycaemia using the glucose-6-phosphatase (G6Pase) system. This system is in the endoplasmic reticulum (ER) and is composed of two functionally linked proteins, a G6P transporter subunit (G6PT) and a catalytic subunit called G6P phosphatase (G6Pase). The G6PT subunit promotes the storage of G6P inside the ER, while G6Pase, which has its catalytic domain in the reticular lumen, hydrolyses G6P to yield free glucose + phosphate. The free glucose stored in the reticular lumen can be transported to the cytosol and from there to the extracellular space in hypoglycaemic conditions by a direct mechanism that has not yet been established, but eventually by glucose transporters (GLUTs).

 

Full text

 

Current Issue

Raptor levels are critical for β-cell adaptation to a high-fat diet in male mice

Manuel Blandino-Rosano, Ruy Andrade Louzada, Joao Pedro Werneck-De-Castro, Camila Lubaczeuski, ... Ernesto Bernal-Mizrachi

Raptor levels are critical for β-cell adaptation to a high-fat diet in male mice

Objective

The essential role of raptor/mTORC1 signaling in β-cell survival and insulin processing has been recently demonstrated using raptor knock-out models. Our aim was to evaluate the role of mTORC1 function in adaptation of β-cells to insulin resistant state.

Method

Here, we use mice with heterozygous deletion of raptor in β-cells (βraHet) to assess whether reduced mTORC1 function is critical for β-cell function in normal conditions or during β-cell adaptation to high-fat diet (HFD).

Results

Deletion of a raptor allele in β-cells showed no differences at the metabolic level, islets morphology, or β-cell function in mice fed regular chow. Surprisingly, deletion of only one allele of raptor increases apoptosis without altering proliferation rate and is sufficient to impair insulin secretion when fed a HFD. This is accompanied by reduced levels of critical β-cell genes like Ins1, MafAUcn3Glut2Glp1r, and specially PDX1 suggesting an improper β-cell adaptation to HFD.

Conclusion

This study identifies that raptor levels play a key role in maintaining PDX1 levels and β-cell function during the adaptation of β-cell to HFD. Finally, we identified that Raptor levels regulate PDX1 levels and β-cell function during β-cell adaptation to HFD by reduction of the mTORC1-mediated negative feedback and activation of the AKT/FOXA2/PDX1 axis. We suggest that Raptor levels are critical to maintaining PDX1 levels and β-cell function in conditions of insulin resistance in male mice.

Articles in Press

Raptor levels are critical for β-cell adaptation to a high-fat diet in male mice

Manuel Blandino-Rosano, Ruy Andrade Louzada, Joao Pedro Werneck-De-Castro, Camila Lubaczeuski, ... Ernesto Bernal-Mizrachi

Raptor levels are critical for β-cell adaptation to a high-fat diet in male mice

Objective

The essential role of raptor/mTORC1 signaling in β-cell survival and insulin processing has been recently demonstrated using raptor knock-out models. Our aim was to evaluate the role of mTORC1 function in adaptation of β-cells to insulin resistant state.

Method

Here, we use mice with heterozygous deletion of raptor in β-cells (βraHet) to assess whether reduced mTORC1 function is critical for β-cell function in normal conditions or during β-cell adaptation to high-fat diet (HFD).

Results

Deletion of a raptor allele in β-cells showed no differences at the metabolic level, islets morphology, or β-cell function in mice fed regular chow. Surprisingly, deletion of only one allele of raptor increases apoptosis without altering proliferation rate and is sufficient to impair insulin secretion when fed a HFD. This is accompanied by reduced levels of critical β-cell genes like Ins1, MafAUcn3Glut2Glp1r, and specially PDX1 suggesting an improper β-cell adaptation to HFD.

Conclusion

This study identifies that raptor levels play a key role in maintaining PDX1 levels and β-cell function during the adaptation of β-cell to HFD. Finally, we identified that Raptor levels regulate PDX1 levels and β-cell function during β-cell adaptation to HFD by reduction of the mTORC1-mediated negative feedback and activation of the AKT/FOXA2/PDX1 axis. We suggest that Raptor levels are critical to maintaining PDX1 levels and β-cell function in conditions of insulin resistance in male mice.

2021 impact factor: 8.568

You are what you eat

Here is a video of Vimeo. When the iframes is activated, a connection to Vimeo is established and, if necessary, cookies from Vimeo are also used. For further information on cookies policy click here.

Auf Werbeinhalte, die vor, während oder nach Videos von WEBSITE-URL eingeblendet werden, hat WEBSITE-URL keinen Einfluss. Wir übernehmen keine Gewähr für diese Inhalte. Weitere Informationen finden Sie hier.