Research
Hormonal
SIRT4 regulates amino acid-stimulated insulin secretion (AASIS) by ADP-ribosylating and inhibiting glutamate dehydrogenase (GDH), linking energy limitation to insulin release.
SIRT4 helps the body decide when to release insulin in response to protein intake. During calorie restriction, SIRT4 levels drop, allowing more insulin to be released in response to amino acids, shifting the source of insulin triggers from carbohydrates to proteins.
GoodSupportsHIGH confidence
SIRT4 plays an important role in regulating amino acid-stimulated insulin secretion (AASIS) in pancreatic beta-cells by ADP-ribosylating and inhibiting glutamate dehydrogenase (GDH)... Down-regulation of SIRT4 during CR appears to mediate this effect because GDH from islets of CR mice is less ADP-ribosylated and more active than GDH from control islets.
Why this rating
Supported by studies in SIRT4 knockout mice and CR mice.
Source
Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction
Marcia C. Haigis et al. · Genes & Development · 2006
DOI 10.1101/gad.1467506
narrative_reviewCited 1,296×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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