| First Author | Sharma AK | Year | 2019 |
| Journal | iScience | Volume | 21 |
| Pages | 736-753 | PubMed ID | 31734536 |
| Mgi Jnum | J:311519 | Mgi Id | MGI:6717514 |
| Doi | 10.1016/j.isci.2019.10.066 | Citation | Sharma AK, et al. (2019) Secretagogin Regulates Insulin Signaling by Direct Insulin Binding. iScience 21:736-753 |
| abstractText | Secretagogin (SCGN) is a beta-cell enriched, secretory/cytosolic Ca(2+)-binding protein with unknown secretory regulation and functions. Recent findings suggest that SCGN deficiency correlates with compromised insulin response and diabetes. However, the (patho)physiological SCGN-insulin nexus remains unexplored. We here report that SCGN is an insulin-interacting protein. The protein-protein interaction between SCGN and insulin regulates insulin stability and increases insulin potency in vitro and in vivo. Mutagenesis studies suggest an indispensable role for N-terminal domain of SCGN in modulating insulin stability and function. SCGN supplementation in diabetogenic-diet-fed mice preserves physiological insulin responsiveness while relieving obesity and cardiovascular risk. SCGN-insulin interaction mediated alleviation of hyperinsulinemia by increased insulin internalization, which translates to reduced body fat and hepatic lipid accumulation, emerges as a plausible mechanism for the preservation of insulin responsiveness. These findings establish SCGN as a functional insulin-binding protein (InsBP) with therapeutic potential against diabetes. |
