When obese diabetic animals (Zucker diabetic fatty rats) were fed large amounts of glucose, the amount of glucose in their blood increased to a higher level, and was maintained longer than the corresponding glucose levels of non-diabetic animals.
The data in the experiments shows that treatment with arimoclomol significantly improved the ability of diabetic animals to remove glucose from the bloodstream after consuming large amounts of glucose.
“The data suggests that arimoclomol may have significant therapeutic benefits for patients with type 2 diabetes,” said Dr Louis Ignarro, CytRx’s chief scientific spokesman.
“This improved glucose tolerance is also seen with certain commonly prescribed diabetic drugs called thiazolidinediones, however these drugs have the unfortunate side effect of significantly increasing overall body weight. The animals treated with arimoclomol alone maintained normal weight.”
In another experiment, rats were given diabetes by feeding them a high fat diet. It is believed that the accumulation of fat in internal organs (visceral fat), rather than overall body fat, may lead to type 2 diabetes. The tissues become less responsive to insulin signaling, causing insulin resistance, one of the earliest signs of diabetes.
CytRx’ new data shows that arimoclomol lowered the amount of fat in the serum of the rats that were fed a high fat diet and also inhibited the accumulation of fat in the liver and muscle tissue of these animals. Arimoclomol did not prevent overall weight gain during the high fat diet, but lowered the amount of visceral fat that accumulated, specifically in liver and muscle tissue.
“If these results can be achieved in humans, it may help prevent the progression of type 2 diabetes in obese patients by preventing insulin resistance,” said Dr Ignarro.
CytRx has also made public data from another past experiment in which arimoclomol was tested for its ability to control the production of glucose in the liver of diabetic animals.
The experiment was performed both in non-obese rats that were genetically predisposed to type 2 diabetes (Goto-Kakizaki diabetic rats) and in genetically normal rats made diabetic by inhibiting their ability to produce insulin with a toxin called streptozoticin. In both experimental models, arimoclomol significantly inhibited the production of glucose in the liver.
Arimoclomol is believed to function by a mechanism that stimulates a normal cellular protein repair pathway through the activation of molecular chaperones. Since damaged proteins called aggregates are thought to play a role in many diseases, CytRx believes that activation of molecular chaperones with arimoclomol could show therapeutic efficacy over a broad range of diseases.