| Autor: |
Anand Kumar Sharma, Radhika Khandelwal, M. Jerald Mahesh Kumar, N. Sai Ram, Amrutha H. Chidananda, T. Avinash Raj, Yogendra Sharma |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
iScience, Vol 21, Iss , Pp 736-753 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2019.10.066 |
| Popis: |
Summary: Secretagogin (SCGN) is a β-cell enriched, secretory/cytosolic Ca2+-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. : Molecular Interaction; Endocrinology; Diabetology; Specialized Functions of Cells Subject Areas: Molecular Interaction, Endocrinology, Diabetology, Specialized Functions of Cells |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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