Abstract

IMG-1 is a novel compound that has been shown to successfully treat type 2 diabetes in ZDF rats and decrease insulin resistance by suppressing HGP and increasing hepatic insulin action in DIO mice. To test the efficacy of IMG-1 to treat type I diabetes Streptozotocin (STZ)-induced diabetic models were employed. In the first study C57BL/6J mice were treated with STZ (50mg/kg) for 5 days to induce diabetes. The animals were either administered IMG-1 or PBS via oral gavage daily for 29 days. Blood glucose (BG) levels were evaluated three times weekly and insulin was measured twice weekly. After 17 days of treatment, IMG-1 treated animals displayed a significant decrease in BG levels (200-300 mg/dl) that persisted for the remainder of the study, while the control animals had continuously high BG levels (400-600 mg/dl). Insulin levels were low in these animals and unaffected by IMG-1. This finding was mimicked in a second experiment where a STZ rat model was used where Sprague-Dawley rats were given a single injection of STZ (60mg/kg) to induce diabetes. In the rat model, the IMG-1 treated animals had significantly lower BG levels by day 9 and remained low for the entire study (200-300 mg/dl). Total bilirubin, ALP, ALT, AST, BUN and creatinine levels were assessed following the 29-day study to determine liver and kidney toxicity. Bilirubin, BUN and creatinine levels were within the normal range, while the ALP, ALT and AST levels were elevated with the STZ treatment (common in this model). IMG-1 did not have any effect on the liver enzymes compared to control. IMG-1 can regulate BG levels in type I diabetic animal models and does not affect kidney or liver function. Disclosure J.B. Pollett: Employee; Self; Imagine Pharma. H. Noh: None. J.K. Kim: None. N. Thai: Board Member; Self; Imagine Pharma.

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