Table 2.

Milk-derived amino acid signals that activate mTORC1-dependent translation.

Milk Amino Acid	Function	References
Leucine (Leu)	Leu stimulates intestinal production of GIP by K-cells augmenting insulin production. Insulin stimulates mTORC1 of peripheral cells of the body.	[72,75,76]
	Leu stimulates intestinal production of GLP-1 by L-cells promoting the production of insulin activating mTORC1. GLP-1 stimulates islet cell DNA replication via activation of mTORC1 involving IGF-1 signaling.	[73,75,77]
	Leu stimulates insulin production of pancreatic β-cells. Insulin stimulates mTORC1 of peripheral cells.	[57,58,62,63]
	Leu allosterically activates GDH, the rate-limiting enzyme of glutaminolysis, which activates mTORC1. GDH contributes to Leu sensing in the regulation of autophagy.	[55,56]
Glutamine (Gln)	Gln promotes cellular uptake of Leu that is the primary amino acid for mTORC1 activation. mTORC1 activation stimulates the uptake of Gln by positive regulation of glutaminase.	[52,53,91]
	Gln is the precursor of the glutaminolysis pathway that activates mTORC1 and mTORC1-dependent insulin synthesis.	[44,54,57]
	Gln controls the activity of the β-cell IGF-2/IGF1R autocrine loop by increasing biosynthesis and secretion of IGF-2.	[90]
Tryptophan (Trp)	Trp induces hepatic IGF1 gene and IGF-1 protein expression. Insulin co-stimulates hepatic IGF-1 secretion.	[81,82]
	Trp via conversion to 5-HT enhances glucose-stimulated insulin secretion, thereby promotes mTORC1 activation.	[78,79,80]
Arginine (Arg)	The amino acid transporter SLC38A9 is a key component of a lysosomal membrane complex that signals Arg sufficiency to mTORC1.	[60]