A researcher from the Indian Institute of Technology Mandi has unraveled the mechanism by which insulin overload in the body causes insulin resistance that is associated with diabetes.

The researcher noted that the drug that is used in treating opioid addiction can potentially reverse the insulin overload phenomenon.

The results of the research work, funded by the Science & Engineering Research Board (SERB) grant, have recently been published in the Journal of Biological Chemistry.

Insulin, a hormone produced by the pancreas, is used by cells to absorb glucose from the blood. Type-2 Diabetes results when cells lose their ability to use insulin due to a variety of reasons.

The researchers noted in their study that 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.

Mondal said in an official statement: “We’ve known that one of the causes of insulin resistance is inflammation. We wanted to find out if and how hyperinsulinemia invokes inflammation in the body, which would provide the link between the two conditions.”

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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 team has also discovered a solution to this problem. 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.

Mondal added: “Naltrexone at low doses could potentially restore some of the diabetes-associated events in cellular and animal models.” He believes 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.

“India is the diabetes capital of the world”, says Mondal of IIT Mandi, adding that one of every six diabetics in the world is Indian.

“It is important to understand the various causative factors for diabetes to find cures and management strategies”, said the lead researcher.

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