Rheb1 as a novel β-cell regulator connecting mTORC1, AMPK, and NOTCH1 pathways for efficient diabetes therapy

Table 1 Comparative analysis between Yang et al’s study[3] and the prior studies in the field of Ras homolog enriched in brain 1 binds

Aspect	Yang et al’s study[3]	Prior studies	Implications	Ref.
Rheb1 & β-cell proliferation	Dual regulation via mTORC1 and AMPK (Figure 4 in the study of Yang et al[3])	mTORC1 alone drives β-cell growth	Reveals AMPK as a critical co-regulator	[16]
β-cell identity	NOTCH1 activation prevents dedifferentiation (Figure 5 in the study of Yang et al[3])	mTORC1 maintains identity	Suggests NOTCH1 as a new therapeutic axis	[5]
HNF4α interaction	Rheb1 binds and upregulates HNF4α (Figure 6 in the study of Yang et al[3])	HNF4α mutations cause MODY1	Links Rheb1 to genetic diabetes mechanisms	[13]
Age-dependent Rheb1	Higher in young human islets (Figure 1A in the study of Yang et al[3])	β-cell replication declines with age	Supports rejuvenation strategies targeting Rheb1	[8]

Rheb1: Ras homolog enriched in brain 1; mTORC1: Mammalian target of rapamycin complex 1; AMPK: AMP-activated protein kinase; NOTCH1: Neurogenic locus notch homolog protein 1; HNF4α: Hepatocyte nuclear factor 4 alpha; MODY1: Maturity-onset diabetes of the young 1.