Inhibiting Ubc9 enzyme could treat type 2 diabetes, researchers suggest
American researchers have targeted the Ubc9 enzyme as a potential treatment target for people with type 2 diabetes.
Ubc9 was confirmed by the Baylor College of Medicine to suppress activity of the peroxisome proliferator-activated receptor y (PPARy). PPARy promotes insulin sensitivity and a positive balance between white and brown fat cells.
A team led by Sean Hartig, PhD, observed that Ubc9 inhibited white fat cells from acting more like fat-burning brown fat cells. As a result, less sugar and fat is burned, which can lead to insulin resistance.
In one experiment, Hartig’s team used a high-throughput microscopy screen to conclude that “[Ubc9] was the most potent suppressor of energy storage in our screen as measured by increased lipid accumulation upon silencing of Ubc9 expression.”
In human patients with diabetes and insulin resistance, Ubc9 was significantly elevated in subcutaneous adipose tissue, but researchers observed treatment with thiazolidinediones (TZDs), a class of PPARy agonist drugs for diabetes, reduced the interaction between Ubc9 and PPARy activity.
“We expect that Ubc9 inhibition in conjunction with TZD treatment would synergistically improve insulin sensitivity by stimulating the thermogenic gene program in subcutaneous adipose tissue,” the researchers wrote.
“Targeted disruption of Ubc9 activity therefore potentially represents a rational approach to increase the therapeutic benefits and potency of insulin-sensitising drugs.”
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