PT  - JOURNAL ARTICLE
AU  - Anand Kumar Sharma
AU  - Radhika Khandelwal
AU  - Swathi Chadalawada
AU  - N Sai Ram
AU  - T Avinash Raj
AU  - M Jerald Mahesh Kumar
AU  - Yogendra Sharma
TI  - SCGN Administration prevents Insulin Resistance and Diabetic Complications in High-Fat Diet Fed Animals
AID  - 10.1101/189324
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 189324
4099  - http://biorxiv.org/content/early/2017/09/15/189324.short
4100  - http://biorxiv.org/content/early/2017/09/15/189324.full
AB  - Secretagogin (SCGN) is poorly-studied secretory/cytosolic CaBP enriched in pancreatic β-cells. Recent studies implicated SCGN in diabetes; however, its function and therapeutic prospect remain uncharted. Based on the apparent synchrony of SCGN and insulin secretion (and its disruption in HFD-fed animals) and considering SCGN downregulation in Type 2 diabetes, we hypothesized that SCGN is a key regulator of insulin response. To test this, we administered rSCGN to HFD-fed animals. We here report that a novel SCGN-insulin interaction stabilizes insulin and potentiates insulin action. Moreover, a chronic rSCGN administration improves insulin response and alleviates obesity associated risk factors such as weight gain, liver steatosis and cholesterol imbalance in DIO animals. Beside the anti-diabetic effects, prolonged rSCGN treatment also induces β-cell regeneration. These effects seem to originate from SCGN mediated regulation of insulin concentration & function as validated in insulin-deficient STZ animals. Our results demonstrate the prospects of the therapeutic potential of SCGN against diabetes.