Isthmin-1 (human) ELISA Kit

Isthmin-1 (ISM1) was first identified as a gene expressed in the Xenopus midbrain-hindbrain organizer called the isthmus, with a proposed role during early brain development. Isthmin-1 encodes a predicted ~50kDa protein containing a signal peptide, a thrombospondin domain and an adhesion-associated domain. Isthmin-1 is important for embryonic and postnatal development. Growing evidence has shown that aberrant expression of Isthmin-1 can also affect the biological behavior of cancer. The Ism1 gene is conserved in mice and humans. A recent study showed that Isthmin-1 is an adipokine that induces glucose uptake in human and mouse adipocytes. Mature adipocytes secrete isthmin-1 and trigger a signaling cascade similar to that of insulin, regulating glucose uptake while suppressing lipid accumulation.

Recombinant Isthmin-1 or overexpression of Isthmin-1 causes a robust increase in GLUT4-dependent glucose uptake in cultured primary murine and immortalized human adipocytes as well as in primary human muscle cells and prevents insulin resistance and hepatic steatosis in a diet-induced obesity mouse model. Ablation of Isthmin-1 causes glucose intolerance and impaired insulin-stimulated adipocyte glucose uptake. Isthmin-1 suppresses de novo lipogenesis and increases protein synthesis in hepatocytes whereas Isthmin-1 knockdown in adipocytes reduces glucose uptake and insulin-dependent phosphorylation of protein kinase AKT at serine residue 473 (p-AKT^Ser473). Isthmin-1 signaling is dependent on PI3K and shares downstream phosphorylation targets with insulin signaling, such as p-AKT^Ser473, p-AKT^Thr308, p-ERK1/2^{Thr202/Tyr204} and p-S6^Ser235/236. Isthmin-1 does not seem to act through the insulin receptor or the insulin-like growth factor 1 receptor; it is most likely to signal through another, yet-to-be-identified, receptor tyrosine kinase.

Isthmin-1 levels positively correlate with obesity in human plasma and are also associated with T cell depletion markers (PD-1, LAG-3, TIM-3 or CTLA-4), suggesting its use as a biomarker during immunotherapy.