PMID:23092880

Citation	Le Bacquer, O, Queniat, G, Gmyr, V, Kerr-Conte, J, Lefebvre, B and Pattou, F' (2012) mTORC1 and mTORC2 regulate insulin secretion through Akt in INS-1 cells. J. Endocrinol. '
Abstract	Raptor (Regulated associated Protein of mTOR) and rictor (rapamycin-insensitive companion of mTOR) are two proteins that delineate two different mTOR complexes, mTORC1 and mTORC2 respectively. Recent studies demonstrated the role of rictor in the development and function of b-cells. mTORC1 has long been known to impact b-cell function and development. However, most of the studies evaluating its role used either drug treatment (i.e. rapamycin) or modification of expression of proteins known to modulate its activity, and the direct role of raptor on insulin secretion is unknown. In this study, using siRNA, we investigated the role of raptor and rictor on insulin secretion and production in INS-1 cells and the possible crosstalk between their respective complex, mTORC1 and mTORC2. Reduced expression of raptor is associated with increased glucose-stimulated insulin secretion and intracellular insulin content. Downregulation of rictor expression leads to impaired insulin secretion without affecting insulin content, and is able to correct the increased insulin secretion mediated by raptor siRNA. Using dominant-negative or constitutively active forms of Akt, we demonstrate that both the effect of raptor and rictor are mediated through alteration of Akt signalling. Our finding shed new light on the mechanism of control of insulin secretion and production by the mammalian target of rapamycin, and they demonstrate that raptor and rictor have antagonistic effects on insulin secretion in response to glucose by modulating the activity of Akt, whereas only raptor is able to control insulin biosynthesis.
Links	PubMed Online version:10.1530/JOE-12-0351
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:RPTOR		GO:0046676: negative regulation of insulin secretion	ECO:0000315:		P		Fig.1D, insulinn secretion at 20mmol/l glucose was increased in the Raptor treated cells.	complete CACAO 5584
MOUSE:RPTOR		GO:0004674: protein serine/threonine kinase activity	ECO:0000314:		F		Fig 3 shows the effect of mutations of the akt activity	complete CACAO 5923
MOUSE:RPTOR		GO:0001932: regulation of protein phosphorylation	ECO:0000315:		P		Figure 3 shows regulation of akt phosphorylation	complete CACAO 6192
MOUSE:RPTOR		GO:0061179: negative regulation of insulin secretion involved in cellular response to glucose stimulus	ECO:0000315:		P		Figure 1 shows Inhibition of raptor expression stimulates insulin secretion in INS-1 cells.	complete CACAO 7023
MOUSE:RPTOR	involved_in	GO:0001932: regulation of protein phosphorylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:RPTOR	involved_in	GO:0046676: negative regulation of insulin secretion	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:RICTR		GO:0004674: protein serine/threonine kinase activity	ECO:0000314:		F		figure 3 shows the effect of mutations of the akt activity	complete CACAO 5919
MOUSE:RICTR		GO:0001932: regulation of protein phosphorylation	ECO:0000315:		P		Figure 3A shows regulation of akt phosphorylation.	complete CACAO 6199
MOUSE:RICTR	involved_in	GO:0001932: regulation of protein phosphorylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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