When you’re hurt or sick with infection, your immune system kicks in to fix the problem. It sends soldiers to fight the bacteria or viruses, medics to repair the damaged cells, and relief workers to clean up the mess. All of these steps are involved in a condition known as inflammation.
“Inflammation is a series of reactions that respond to harmful stimuli including viral or bacterial infections, damaged cells and other allergens,” says Jongsoon Lee, Ph.D., Investigator in the Section on Pathophysiology & Molecular Pharmacology, who studies inflammation and diabetes at Joslin Diabetes Center. The immune system controls (or regulates) cells that either increase or decrease inflammation in response to bodily damage, a process that is usually beneficial.
Inflammation is necessary to healing, but if the typically helpful process starts to run rampant it can lead to a number of health problems.
“One extreme example is sepsis,” says Dr. Lee. “With infection, immune cells in the host try to remove the virus or bacteria and the infected cells by producing inflammatory mediators (typically pro-inflammatory mediators). However, in some cases (sepsis), they produce too many of these inflammatory mediators, which causes death of both the infected cells as well as the non-infected normal cells eventually leading to death of the [ill person].”
Inflammation also plays a major role in autoimmune diseases such as type 1 diabetes. The inflammatory cells from the immune system fight off proteins that are supposed to be part of the body instead of focusing on bacteria and viruses.
And recent research suggests that obesity can trigger an inflammatory reaction that leads to insulin resistance. Several studies following individuals’ medical histories show that the higher the patient’s body mass index, the higher the level of circulating inflammatory mediators in the blood, leading to a higher risk for developing type 2 diabetes down the line.
Dr. Lee studies the development of obesity-induced inflammation and its relationship to type 2 diabetes. He thinks inflammation as related to obesity develops differently than the inflammation that leads to arthritis or type 1 diabetes.
“Therefore we are investigating the obesity-specific cellular and molecular pathway(s) that promote the development of obesity-induced inflammation and insulin resistance,” he says.
To do this, his lab is looking at how the inflammation process changes when the genes or cells responsible for obesity-induced inflammation are modified or manipulated. They are comparing normally-developed obesity-induced inflammation with the modified process to watch for differences in immune function and metabolism.
Previous studies have shown in animal models that decreasing inflammation improves insulin sensitivity. “The idea that obesity-induced inflammation causes the development of insulin resistance, at least in animal models, is gaining support,” he says. Dr. Lee’s current studies are probing deeper into the problem to understand the why that seems to be the case.
But he also notes that just because something is true in animal models, it doesn’t necessarily translate into humans. “A few of these [animal] studies have been translated into clinical trials but occasionally have had mixed results,” he said.
One of the examples for those translational studies is a Joslin study in 2013 led by Allison Goldfine, M.D., co-head of the Clinical Research Center at Joslin Diabetes Center, and Steve Shoelson, M.D., Ph.D., Head of the Section of Pathophysiology and Molecular Pharmacology at Joslin Diabetes Center. This study showed that an aspirin-like medication known as salicylate that decreases inflammation improved glycemic control in people with type 2 diabetes. More follow-up studies should allow researchers to pinpoint the reasons why this generic drug worked, and create other similar medications.
Dr. Lee’s lab is working in animal models now, but the goal is to identify which pathways in the inflammatory process are responsible for the development of obesity-induced insulin resistance and could be altered by medication to improve insulin sensitivity. They would then test those newfound pathways in human studies.