the researchers Indian Institute of Technology (IIT) Mandi Claims to have identified a molecule that can be used to treat diabetes. Researchers claim that this molecule, called PK2, can trigger the release of insulin by the pancreas and could potentially be used as an orally administered drug for diabetes.
Explaining the rationale, Dr Prosenjit Mandal, Associate Professor, School of Basic Sciences at IIT Mandi, said, “Existing drugs such as exenatide and liraglutide used for diabetes are administered as injections, and they After administration are expensive and unstable. We want to find simple drugs that are stable, affordable and effective against both type 1 and type 2 diabetes.”
To find alternatives to these drugs, the multi-institutional team first used computer simulation methods to screen various small molecules that might bind to the GLP1R. While PK2, PK3, and PK4 had good binding abilities with GLP1R, they chose PK2 because of the latter’s better solubility in solvents. The researchers then synthesized PK2 in the laboratory for further testing.
Elaborating on the initial research, Dr Khyati Girdhar said, “We first tested the binding of PK2 on GLP1R protein in human cells and found that it is able to bind well to GLP1R protein. This showed that PK2 could potentially trigger insulin release by beta cells.” The researchers found that PK2 was rapidly absorbed by the gastrointestinal tract, meaning it could be used as an oral drug rather than as an injection. Furthermore, after two hours of administration, PK2 was found to be distributed in the liver, kidney and pancreas of mice, but there was no trace of it in the heart, lung and spleen. Small amounts were present in the brain, suggesting that the molecule may be able to cross the blood–brain barrier. It was taken out of circulation in about 10 hours.
Dr. Prosenjit Mondal also points to another important finding in his work, “Beyond increasing insulin release, PK2 was able to prevent and even reverse beta cell loss, insulin production.” cells, making it effective for both type 1 and type 2. diabetes.”
To test the biological effects of PK2, the researchers administered it orally to experimental mice that developed diabetes and measured glucose levels and insulin secretion. There was a six-fold increase in serum insulin levels in PK2-treated mice over the control group. These findings offer hope for affordable oral drugs for diabetics. The research findings have been published in the Journal of Biological Chemistry.
This paper is authored by Dr. Prosenjit Mandal, Associate Professor, School of Basic Sciences, and co-authored with Professor Subrata Ghosh, School of Basic Sciences, IIT Mandi, Dr. Sunil Kumar, ICAR-IASRI, Pusa, New. Delhi, Dr. Budheshwar Dehuri, ICMR RMRC, Bhubaneswar, Dr. Khyati Girdhar, Shilpa Thakur, Dr. Abhinav Choubey, Dr. Pankaj Gaur, Surbhi Dogra, Ms. Bidisha Biswas from IIT Mandi, and Dr. Durgesh Kumar Dwivedi (Regional Ayurvedic Research Institute (Regional Ayurvedic Research Institute) Institute) Rari) Gwalior).
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