Insulin Suppresses Receptors that Cause Cascade of Inflammation, Study Shows

Insulin appears to suppress a particular group of inflammatory mediators known as toll-like receptors, or TLRs, which are critical to the inflammatory process.

TLRs are a variety of pattern-recognition receptors that identify bacterial and viral products and other pathogens.

UB researchers have found that insulin interferes with the expression of several types of TLRs, likely by suppressing a specific transcription factor known as PU.1, which is known to regulate TLR expression.

"We reported earlier that an infusion of low-dose insulin exerts a quick, powerful anti-inflammatory effect in diabetic patients," said Paresh Dandona, M.D., Ph.D., UB Distinguished Professor of Medicine, chief of the Division of Endocrinology in UB's Department of Medicine, School of Medicine and Biomedical Sciences, and senior researcher on the project.

Dandona also is chief of Kaleida Health's Division of Endocrinology and director of Kaleida's Diabetes-Endocrine Center of Western New York, where he conducted his research.

"Knowing that toll-like receptors are major determinants of the body's inflammatory response to viral and bacterial pathogens, we set out to see if these receptors were susceptible to insulin's effect," said Dandona.

"We've now shown for the first time that an infusion of low dose insulin suppresses expression of five TLR subtypes and the DNA binding of PU.1."

Husam Ghanim, Ph.D., research assistant professor in UB's Division of Endocrinology, Diabetes and Metabolism, is first author on the study, which was published online June 12 in Diabetes Care ahead of print.

TLRs have been shown to play a role in many inflammation conditions, including atherosclerosis, endotoxin shock, insulin resistance and diabetes, lupus, the destruction of insulin producing cells and insulin resistance in type 2 diabetes.

The current study was conducted in 24 patients with Type 2 diabetes. Researchers infused 10 obese Type 2 diabetics with a low dose of insulin plus a sugar solution to maintain correct glucose levels, while a similar group of 14 received either a sugar or saline solution to serve as controls. Both groups were infused for four hours.

Expression of TLRs was measured in white blood cells prepared from blood samples collected before the start of the infusion, and at 2, 4 and 6 hours after the infusion began.

Results showed that the levels of TLRs dropped significantly within 2 hours in the insulin group and reached the maximum reduction at 4 hours. Specifically, at 4 hours insulin suppressed levels of TLR 1, 2, 4, 6, and 9 by approximately 24 percent, 21 percent, 30 percent, 28 percent and 27 percent, respectively. At the same time, the DNA binding of PU.1 was suppressed by 24 percent.

Meanwhile, neither TLR expression nor PU.1 DNA binding were affected in those who received dextrose or saline.

"These data further support the concept that insulin is anti-inflammatory and that it may have potential use in treating various infective inflammatory conditions as well as acute coronary syndromes," Dandona said. "This includes acute myocardial infarction and cardiac surgery, where inflammation plays an important role."

Priya Mohanty, M.D., Rupali Deopurkar, M.D., Ph.D., Ching Ling Sia, Kelly Korzeniewski, Sanaa Abuaysheh, and Ajay Chaudhuri, M.D., all from Dandona's research group, also contributed to the study.

Provided by University at Buffalo

Not all fat is created equal
A Temple University study finds fat in obese patients is "sick" when compared to fat in lean patients.
Researchers turn one form of adult mouse cell directly into another
(PhysOrg.com) -- In a feat of biological prestidigitation likely to turn the field of regenerative medicine on its head, Harvard Stem Cell Institute (HSCI) co-director Doug Melton and post doctoral fellow Qiao "Joe" Zhou report having achieved what has long been a dream and ultimate goal of developmental biologists – directly turning one type of fully formed adult cell into another type of adult cell.
Young type-2 diabetic men suffer low testosterone levels, study shows
Young men with type 2 diabetes have significantly low levels of testosterone, endocrinologists at the University at Buffalo have found -- a condition that could have a critical effect on their quality of life and on their ability to father children.
Caesarean babies more likely to develop diabetes
Babies delivered by Caesarean section have a 20 per cent higher risk than normal deliveries of developing the most common type of diabetes in childhood, according to a study led by Queen's University Belfast.
Potential diabetes treatment selectively kills autoimmune cells from human patients
In experiments using blood cells from human patients with diabetes and other autoimmune disorders, Massachusetts General Hospital (MGH) researchers have confirmed the mechanism behind a potential new therapy for type 1 diabetes. A team led by Denise Faustman, MD, PhD, director of the MGH Immunobiology Laboratory, showed that blocking a metabolic pathway regulating the immune system specifically eliminated immune cells that react against a patient's own tissues.
Scientists discover leptin can also aid type 1 diabetics
Terminally ill rodents with type 1 diabetes have been restored to full health with a single injection of a substance other than insulin by scientists at UT Southwestern Medical Center.
Joslin study identifies protein that produces 'good' fat
A study by researchers at the Joslin Diabetes Center has shown that a protein known for its role in inducing bone growth can also help promote the development of brown fat, a "good" fat that helps in the expenditure of energy and plays a role in fighting obesity.
Researcher develops novel method to grow human embryonic stem cells
(PhysOrg.com) -- The majority of researchers working with human embryonic stem cells (hESCs) – cells which produce any type of specialized adult cells in the human body – use animal-based materials for culturing the cells. But because these materials are animal-based, they could transmit viruses and other pathogens to the hESCs, making the cells unsuitable for medical use.

Insulin Suppresses Receptors that Cause Cascade of Inflammation, Study Shows

Related stories:

News discussion: