Jahnavi Sarma
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Written By: Jahnavi Sarma | Updated : July 31, 2020 10:16 AM IST
The potential drug could be beneficial in both Type 1 and Type 2 diabetes, including both lean and obese individuals. @Shutterstock
Diabetes is a disease affecting two hormones -- insulin and glucagon. In healthy individuals, insulin helps cells take up glucose from the blood when glucose levels are high, and glucagon helps the liver release glucose into the bloodstream when glucose levels are low. In diabetes, insulin release is diminished, cell sensitivity to insulin can decrease, and glucagon release is excessive. This can cause a vicious cycle of escalating blood glucose levels.
Now researchers from the University of Alabama at Birmingham and Southern Research have discovered a new drug candidate that offers a major advance in the treatment for diabetes. The drug candidate SRI-37330 is a non-toxic small molecule that effectively rescued mice from streptozotocin- and obesity-induced diabetes and improved glucose homeostasis. It was discovered through two decades of research, followed by screening of 300,000 compounds and extensive medicinal chemistry optimization at Southern Research, headquartered in Birmingham. The journal Cell Metabolism published this study.
Researchers tested this experimental drug on isolated human and mouse pancreatic islets, mouse and rat cell cultures and animal models of both Type 1 and Type 2 diabetes. Thy saw that it significantly improved four adverse characteristics of diabetes: Hyperglycemia, known as high blood sugar; hyperglucagonemia, elevation in the hormone glucagon that counteracts the effects of insulin, promotes glucose production and increases blood glucose; excessive production of glucose by the liver; and fatty liver, known as hepatic steatosis.
According to researchers, this drug has strong anti-diabetic properties. Compared to currently available diabetes therapies, the compound may provide a distinct, effective and highly beneficial approach to treat diabetes. They also say that while the safety and efficacy of SRI-37330 in humans still remains to be determined, it is highly effective in human islets, is orally bioavailable and is well tolerated in mice. SRI-37330 appears to act beneficially on pancreatic islets that produce the two hormones, and also at the liver.
The potential drug could be beneficial in both Type 1 and Type 2 diabetes, including both lean and obese individuals. Also, diabetes appears to be a significant co-morbidity in the current COVID-19 pandemic. The 80 million people in the United States who have prediabetes might also benefit from the potential drug. Furthermore, the effectiveness of SRI-37330 in reducing fatty liver in mice suggested it might have potential to treat non-alcoholic fatty liver disease, which affects about 100 million people in the United States and 1 billion worldwide.
Surprisingly, SRI-37330 decreased blood glucose levels primarily via lowering of serum glucagon levels and inhibition of basal glucose production from the liver. This mode of action is very different from that of currently used anti-diabetic drugs. Despite SRI-37330's reduction of glucagon release from pancreatic islets and reduction of glucose production by the liver, the inhibitor did not cause any low blood glucose events or create a hypoglycemic liability in mice, even in the context of insulin-induced hypoglycemia.
(With inputs from Agencies)
