In a new study that challenges how diabetes is controlled, researchers found boosting the activity of proteins activated by inflammation might be beneficial, contradicting current views. Inflammation brought about by obesity is blamed as a major contributor to type 2 diabetes.…
In the discovery, researchers describe what they call a “paradigm shift” in our understanding of the mechanism of how type 2 diabetes develops and could be managed.
In the study, researchers from Children’s Hospital Boston report that two proteins activated by inflammation normalized blood sugars in diabetic mice.
Umut Ozcan, MD, in the Division of Endocrinology at Children’s Hospital who led the research, stated that, this completely contradicts the notion that inflammation is detrimental for controlling diabetes. Rather, the finding suggests obesity and insulin resistance may destroy the body’s ability to respond to inflammation. Finding ways to boost the inflammatory response could be a new treatment approach.
The research team previously showed that obesity causes endoplasmic reticulum (ER) stress. The endoplasmic reticulum is important for normal cell functioning. ER stress impairs the body’s response to insulin. The scientists also showed a protein called XBP1s, cannot function in obese mice.
Artificially activating the protein in the liver of mice with type 2 diabetes, and also in lean, insulin-deficient type 1 diabetic mice, caused blood sugar levels to return to normal in the mouse studies.
A second protein, called p38 MAPK, which is triggered by inflammation, makes XBP1s more active. Without p38MAPK, XBP1s can’t function to keep blood sugar levels in check.
In the context of the study results, the scientists say using p38 MAPK inhibitors to treat inflammatory diseases such as Crohn’s disease, psoriasis and asthma might be destroying the body’s ability to cope with inflammatory conditions. Studies have been ongoing to find therapeutic applications for drugs that block the protein.
Ozcan says, “It may be that inflammatory pathways are not working optimally and there could be a resistance to cytokines which mediates the inflammation.” “This could be a paradigm shift for the field.”
The research suggests a new approach for understanding the role of inflammation in diabetes that may be beneficial instead of detrimental.
Increasing the inflammatory signaling activity of p38 MAPK or increasing XBP-1 activity could provide a new approach for treating diabetes that contradicts current views of diabetes control.
Nature Medicine (2011) doi:10.1038/nm.2449: “P38 MAPK–Mediated Regulation of Xbp1s is Crucial for Glucose Homeostasis” Jaemin Lee et al.; September 4, 2011