Mitochondrial Changes Cause Inflammation in Type 2 Diabetes

Cause of Inflammation in obesity and type 2 diabetes mellitus (T2DM) helps to develop treatments to prevent complications from the disease which is the third leading cause of death in the United States.

Mitochondrial changes cause chronic inflammation in diabetes when cells get exposed to certain types of fats, according to the new research done by the researchers of the University of Kentucky.

Chronic inflammation fuels many of the devastating complications of type 2 diabetes, including cardiovascular, kidney, and periodontal diseases, and is thus one of the key targets for therapy development. This new data may enlighten the conversation about tight glycemic control as the dominant treatment goal for people with diabetes.

‘Mitochondrial defects and accumulated fat derivatives were responsible for long-term inflammation in type 2 diabetes, which in turn cause various complications. New therapeutic approaches can be designed targeting mitochondrial changes.’
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The research was recently published in Cell Metabolism by a team led by Barbara Nikolajczyk (UK Barnstable Brown Diabetes Center, Department of Pharmacology and Nutritional Sciences) and Douglas Lauffenberger (MIT Department of Biological Engineering).

Nikolajczyk and Lauffenberger didn't set out to disprove the glucose-inflammation causation theory. Based on the importance of glycolysis--a 10-reaction sequence that produces energy--in other types of inflammation, the team hypothesized that immune cells from patients with type 2 diabetes would produce energy by burning glucose. "We were wrong," Nikolajczyk said.

"We exclusively used immune cells from human subjects for all of the work, " Nikolajczyk explained, noting that humans, but not animal models of type 2 diabetes, have the specific pro-inflammatory T cell profile her team had identified in earlier research.

The team was surprised to find that glycolysis wasn't driving chronic inflammation. Instead, a combination of defects in mitochondria and elevated fat derivatives were responsible.

Nikolajczyk said she sees applications for this research in both basic and clinical sciences. She hopes to precisely define pro-inflammatory lipid types and explore associations between circulating and/or tissue-associated lipids and insulin resistance, one key feature of Type 2 diabetes. She is also interested in contributing to the development of new analytical approaches, spearheaded by Dr. Lauffenburger's team, that leverage ongoing lipid-related findings into a new understanding of pathology in type 2 diabetes.

Diabetes Essentials: Types, Complications, Management & Treatment
Diabetes is a metabolic disease caused by insulin deficiency that leads to high blood sugar levels and several associated complications if left untreated.

"Aggressive blood glucose control to lower the risk of diabetic complications has been the goal for most people with Type 2 Diabetes for decades," Nikolajczyk said. "Our data provide an explanation for why people with tight glucose control can nonetheless have disease progression."

Source-Eurekalert