Branching-out: the role of branched-chain amino acid catabolism in insulin resistance and type 2 diabetes

The increasing number of people diagnosed with diabetes (type 2) is a global issue. Reduced sensitivity to insulin is the most significant risk factor for developing diabetes, and it always precedes the onset of the disease. There is evidence that a disruption in the metabolism of branched-chain amino acids, also known as BCAAs, plays an increasingly important role in the development of diabetes. It has been shown that BCAA levels are elevated in the blood of individuals with insulin resistance and diabetes, possibly due to a lower BCAA breakdown. This thesis focuses on the role of BCAA breakdown as a cause of diabetes and promoting BCAA breakdown as a new treatment for diabetes. The studies outlined in this thesis demonstrate that the increased BCAA levels in the blood are associated with the degree of insulin sensitivity and other metabolic disruptions. The results indicate that diabetic patients have impaired BCAA breakdown, which could potentially explain the elevated BCAA levels in these patients. This thesis also demonstrates that stimulating BCAA breakdown improves blood glucose regulation and could, therefore, be a new treatment strategy.