Researchers from the School of Medicine, Trinity College Dublin, say they have, for the first time, discovered a family of proteins that are associated with lower blood sugar levels among obese patients with type 2 diabetes. Their study (“Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction”), published in Nature Communications, showed that patients with type 2 diabetes who have high levels of the protein, IL-36 cytokines, were found to have lower blood sugar levels, implying that those proteins are associated with better control of the patient’s blood sugar levels and their disease.

“IL-36 cytokines are members of a larger family of the IL-1 proteins which have emerged as central players in the development of obesity-related disease. Scientists have linked the protective effects of these proteins with their ability to alter the make-up of the intestinal microbiome.

“Members of the interleukin-1 (IL-1) family are important mediators of obesity and metabolic disease and have been described to often play opposing roles. Here we report that the interleukin-36 (IL-36) subfamily can play a protective role against the development of disease. Elevated IL-36 cytokine expression is found in the serum of obese patients and negatively correlates with blood glucose levels among those presenting with type 2 diabetes,” the investigators wrote.

“Mice lacking IL-36Ra, an IL-36 family signaling antagonist, develop less diet-induced weight gain, hyperglycemia, and insulin resistance. These protective effects correlate with increased abundance of the metabolically protective bacteria Akkermansia muciniphila in the intestinal microbiome. IL-36 cytokines promote its outgrowth as well as increased colonic mucus secretion. These findings identify a protective role for IL-36 cytokines in obesity and metabolic disease, adding to the current understanding of the role the broader IL-1 family plays in regulating disease pathogenesis.”

Obesity causes an increased level of fatty acids and inflammation leading to insulin resistance. When the body is resistant to the insulin it produces it causes a high build-up of glucose or blood sugar, ultimately leading to type 2 diabetes.

Obesity is now recognized as a global pandemic and has been definitively linked to a wide range of diseases including metabolic disorders such as diabetes, stroke, and many types of cancer. The World Health Organization state that global levels of obesity have more than doubled since 1980. In Ireland, according to the Healthy Ireland survey, 854,165 adults over 40 in the Republic of Ireland are at increased risk of developing (or have) type 2 diabetes. The economic burden of diabetes on the Irish health care system is becoming a major challenge for the government.

Given the scale and global reach of the problem, current approaches aimed at reversing the tide of obesity driven disease are insufficient. The Trinity research team believe that there is an urgent need to achieve a greater understanding of the mechanisms associated with obesity-related diseases.

According to lead scientist Patrick Walsh, PhD, from the School of Medicine, Trinity College Dublin, “This study has added to a substantial body of work which has revealed the important function of the broader interleukin-1 family as mediators of metabolic health and disease. Our findings have opened the door to a deeper investigation of how IL-36 cytokines impact on the development of such diseases in humans and whether this can be exploited for the better treatment of patients.”

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