New York, NY (November 21 , 2013 – A single overactive enzyme worsens the two core defects of diabetes impaired insulin sensitivity and overproduction of glucose suggesting that a drug targeting the enzyme could help correct both at once, according to mouse studies done by researchers at Columbia University Medical Center.
Although antidiabetic agents have been developed to target one or more of the core defects of type 2 diabetes mellitus (T2DM), many patients do not achieve glycemic goals.
In summary, the results of the current study demonstrate that Mexican American subjects with HbA1c >6% manifest both core defects of type 2 diabetes in severe form (44 and 74% decrease in insulin sensitivity and β-cell function, respectively).
The core defects of T2DM include quantitative and qualitative β-cell dysfunction, peripheral (skeletal muscle) insulin resistance, and elevated glucose production in the liver, as well as increased lipolysis when obesity is present.
Experimental NEFA elevation to reproduce levels in type 2 diabetes causes severe muscle/liver insulin resistance [ 133– 135] and inhibits insulin secretion [ 136], reproducing the three basic core defects of type 2 diabetes.
The harmful metabolic effects of chronic hyperglycemia associated with the two core defects of T2DM, insulin resistance and partial β-cell failure, can be described as "glucose toxicity", which contributes in turn to further progression of β-cell dysfunction in a vicious cycle of glucose toxicity-induced pathogenesis [ 11, 12].
Pioglitazone is unique in that it both exerts β-cell protective effects (81) and is a powerful insulin sensitizer in muscle and liver (56– 65, 65, 74– 76) Thus, it is the only antidiabetes agent that corrects the core defects of insulin resistance and β-cell failure in T2DM.
This function allows the changes to be visualized as a 2D image of belt core defects on all belt sections and splices.
It is annotated as phosphomannomutase gene and, because of the severe core defect, we proposed before the name of manBcore [11].
Insulin resistance is a core defect in the pathogenesis of type 2 diabetes, and the condition is associated with increased risk for diabetes already in early adulthood (1– 4).
