SHLP-2 (Small Humanin-Like Peptide 2) is one of six mitochondrial-derived peptides (MDPs) discovered in the same mitochondrial genome region encoding humanin.
Discovery & Origin
In silico analysis of the 16S rRNA region revealed six SHLPs (1-6), ranging from 20-38 amino acids. SHLP-2 emerged as particularly significant for metabolic and neuroprotective properties.
Age-Related Decline
Like humanin, circulating SHLP-2 levels decrease with age, coinciding with reduced regenerative capacity and increased metabolic dysfunction.
Mechanism of Action
Insulin Sensitization
SHLP-2 increases glucose uptake and suppresses hepatic glucose production, functioning as an insulin sensitizer both peripherally and centrally.
CXCR7 Binding
SHLP-2 binds CXCR7 receptor, activating hypothalamic neurons regulating food intake, energy expenditure, and glucose homeostasis.
Mitochondrial Protection
- Increases oxygen consumption rate and ATP production
- Protects against mitochondria-mediated apoptosis
- Reduces reactive oxygen species
Chaperone Activity
Targets misfolded amyloid seeds to inhibit IAPP misfolding—key in T2D pathology.
Research Findings
- Both systemic and ICV administration protected mice from high-fat diet-induced obesity
- Protects islet cells from IAPP-related stress
- Lowers age-related metabolic disorder markers
Therapeutic Potential
Significant for T2D, obesity, neurodegeneration, and cardiovascular disease research.