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bioRxiv · 10.1101/189324

SCGN Administration prevents Insulin Resistance and Diabetic Complications in High-Fat Diet Fed Animals

Sharma, A. K.·Khandelwal, R.·Chadalawada, S.·Ram, N. S.·Raj, A.·Mahesh Kumar, J.·Sharma, Y.
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Abstract

Secretagogin (SCGN) is poorly-studied secretory/cytosolic CaBP enriched in pancreatic {beta}-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 {beta}-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.

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Sharma, A. K., Khandelwal, R., Chadalawada, S., Ram, N. S., Raj, A., Mahesh Kumar, J., Sharma, Y.. 2017-09-15. SCGN Administration prevents Insulin Resistance and Diabetic Complications in High-Fat Diet Fed Animals. https://doi.org/10.1101/189324

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