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Bidirectional modulation of insulin action by amino acids
M E Patti1, E Brambilla, L Luzi
1Research Division, Joslin Diabetes Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
The Journal of Clinical Investigation
|April 29, 1998
Summary
Amino acids signal protein synthesis and inhibit insulin
Area of Science:
- Biochemistry
- Cellular Biology
- Metabolic Signaling
Background:
- Amino acids influence protein synthesis and glucose metabolism.
- Their role as signaling molecules in insulin target tissues is not fully understood.
Purpose of the Study:
- To investigate the signaling role of amino acids in insulin target tissues.
- To elucidate the mechanisms by which amino acids modulate insulin action.
Main Methods:
- Utilized cultured hepatoma and myotube cells.
- Assessed the impact of amino acids on protein synthesis intermediates (p70 S6 kinase, PHAS-I).
- Examined effects on insulin signaling pathways, including tyrosine phosphorylation of IRS-1/IRS-2 and phosphatidylinositol 3-kinase activity.
Main Results:
- Amino acids, particularly leucine, synergistically activate protein synthesis with insulin.
- Amino acids inhibit key insulin signaling steps, including IRS-1/IRS-2 phosphorylation and phosphatidylinositol 3-kinase activation.
- Branched-chain amino acids and ketoisocaproic acid replicate these effects.
Conclusions:
- Amino acids act as dual signals: promoting protein synthesis and inhibiting insulin's effects on glucose metabolism.
- Demonstrates crosstalk between hormonal (insulin) and nutritional (amino acid) signals.
- Provides a novel mechanism for how nutritional factors contribute to insulin resistance.
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