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bioRxiv · 10.1101/2021.01.22.427879

Antidiabetic action of Mcy protein through the regulation of number and affinity of insulin receptors

Marella, S.·Kotha, P.·Shaik, A. N.·GIRISH, B.·Badri, K. R.·Chippada, A. R.
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Abstract

Evidence based immunological cross-reactivity studies and anti-diabetic investigations have suggested the presence of insulin-like peptides in plants. Mcy protein, isolated from the fruits of Momordicacymbalaria, was shown to have antihyperglycemic, antihyperlipidemic activities along with renal as well as hepatoprotective activities in Streptozotocin induced diabetic rats.Mcy protein was shown to have insulin like and/or insulin secretagoguestructure and/or functions. Hence, the present study was conducted to elucidate molecular mechanism wherebyMcy protein elicits its therapeutic role and also to know whether the Mcyprotein has any structural and functional similarity with insulin. Results of our experiments revealed that the Mcyprotein is insulin like protein. Further, we assessed the effect of treatment of Mcy protein on the levels of glucose transport (glucose transporter (GLUT-2) and on the levels of key regulators of glucose and lipid metabolisms like hepatic glucokinase (GK) and sterol regulated element binding protein-1c (SREBP-1c). Our findings demonstrated that Mcy protein decreased the elevated expressions of GK, SREBP-1c and GLUT-2 that were observed in diabetic animals. Insulin-receptor binding studies using rat erythrocytes demonstrated that mean specific binding of insulin with insulin receptors was significantly increased in Mcy treated diabetic rats when compared to diabetic control rats. Scatchard analyses of insulin-binding studies yielded curvilinear plots, and the number of receptor sites per cell was found to be 180{+/-}21.1 in Mcy treated diabetic animals calculated to be significantly superior to that of diabetic control animals. Kinetic analyses also revealed an increase in the average receptor affinity of erythrocytes from Mcy treated rats compared to diabetic control rats suggesting acute alteration in the number and affinity of insulin receptors on the membranes of erythrocytes.

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Marella, S., Kotha, P., Shaik, A. N., GIRISH, B., Badri, K. R., Chippada, A. R.. 2021-01-24. Antidiabetic action of Mcy protein through the regulation of number and affinity of insulin receptors. https://doi.org/10.1101/2021.01.22.427879

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