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melior melior melior discovery melior pharmaceuticals preclinical services pre-clinical services in vivo pharmacology in vivo efficacy efficacy models pharmacokinetics indications discovery specialized animal models bioanalytical services theratrace exton pennsylvania cro contract research drug discovery drug development metabolic disease alzheimer’s alzheimers diabetes reprofiling

Melior Discovery metabolic

Insulin Tolerance Test (ITT)
The Insulin Tolerance Test (ITT) is designed to determine the sensitivity of insulin receptors in tissue by measuring blood glucose levels before and after insulin administration. This is a standard test to determine the diabetic status in humans and experimental animals.  This test is used to assess the efficacy of insulin-like compounds and pharmacological agents that can modify insulin responsiveness. 

                    

The graph above illustrates the difference in response to an insulin challenge (ITT) in insulin-depleted (streptozotocin-treated) mice administered insulin, insulin+MLR-1023 or MLR-1023 alone.  This study shows that MLR-1023 significantly extended the duration and magnitude of the insulin response.  Data are mean ± SEM, *p<0.05, ***p<0.001 compared to vehicle.

 

MLR-1023 is a potential "next-generation" insulin sensitizer that works independently of a PPAR mechanism.  This compound improves glycemic control by directly and selectively activating the enzyme Lyn kinase.  Lyn kinase has been previously shown to modulate the insulin-signaling pathway.  MLR-1023 is the first described specific and direct activator of Lyn kinase that elicits glycemic control activity through potentiation of insulin activity.  For more information on MLR-1023, please visit our sister site, Melior Pharmaceuticals

 

In addition to MLR-1023 studies, Melior routinely performs ITT studies in mice fed a "Western diet" that is designed to approximate the "typical" human diet of North America and Europe.  The "Western diet" contains greater than five times more fat than the normal diet.  In this study, mice were fasted four hours prior to study commencement.

 

 

                      

Insulin tolerance test.  A baseline glucose measurement was evaluated one hour prior to dosing.  At time 0 minutes, mice received either insulin or vehicle (no insulin).  Blood glucose measurements were evaluated at 20, 40, 60, and 120 minutes after insulin administration. Administration of insulin induced a signficant decrease in blood glucose levels, beginning 20 minutes post does.  After administration with insulin, there was a significant reduction in blood glucose levels at the 20, 40 and 60-minute time points that return to normal levels 120 minutes after insulin challenge.  Vehicle treated animals showed a consistent measure of blood glucose levels throughout the duration of the study. These data demonstrate that the elevation in blood glucose levels can be significantly reduced using insulin. Data are mean ± SEM, ***p<0.001 compared to vehicle.

 

For more information on the Insulin Tolerance Test (ITT), please contact models@meliordiscovery.com to start the conversation.