Drugs that can reverse Type 2 diabetes

Mandi (Himachal Pradesh) : The Indian Institute of Technology Mandi (IIT Mandi) on Monday said its researchers have unravelled the mechanism by which insulin overload in the body causes insulin resistance which is associated with diabetes.

They have found that the drug used in treating opioid addiction can potentially reverse this phenomenon.

According to the study, published in the Journal of Biological Chemistry, type-2 diabetes results when cells lose their ability to use insulin due to a variety of reasons.

Insulin resistance is intricately linked to a condition called hyperinsulinemia, in which there is excess insulin traversing the bloodstream.

The relationship between insulin resistance and hyperinsulinemia is cyclic — each increases the occurrence of the other.

While it is obvious how insulin resistance leads to hyperinsulinemia — when cells cannot use the insulin, it just remains in the blood — the converse of how hyperinsulinemia increases insulin resistance has hitherto remained unclear.

“We wanted to find out if and how hyperinsulinemia invokes inflammation in the body, which would provide the link between the two conditions,” Dr Prosenjit Mondal, Associate Professor, School of Basic Sciences, IIT Mandi, said in a statement.

The researchers identified a critical protein molecule – SIRT1 which is repressed in hyperinsulinemia.

They discovered that a decrease in SIRT1 activates another protein called NFkB, which instigates inflammation, thus providing the link between hyperinsulinemia and systemic inflammation.

The researchers found that low-dose naltrexone (LDN), a drug commonly administered for opiate addiction, can activate SIRT1, thereby reducing inflammation and increasing insulin sensitivity of cells.

“Naltrexone at low doses could potentially restore some of the diabetes-associated events in cellular and animal models”, said Mondal, who is confident that this is a viable path to follow for Type-2 diabetes management.

Naltrexone is already an FDA-approved drug that is used for the treatment of opioid addiction and can easily be repurposed for inflammation reduction and diabetes control.

The research team intends to study this thread further, to understand the mechanistic aspects of LDN’s effects on hyperinsulinemia-induced inflammation and resulting insulin resistance.