Effect of oligonucleotide (ODN) IMT504 in a type I diabetes model in mice.

CALVO V,; MONTANER A,; LIBERTUN C, ; CHASSEING NA,; LUX V,; BIANCHI MS.

Bs As, Argentina.

Jornada; XII Jornadas de la SAB, Diciembre de 2010; 2010

SAB.

We have previously shown that the oligonucleotide IMT504 induces a marked recovery of streptozotocin (STZ)-induced diabetes in male rats that correlates with early production of progenitor cell markers (Diabetologia 2010, 53: 1184). Here we studied the effect of IMT504 on a type I diabetes model induced by multiple low doses of STZ. 6-8 week-old male BalbC mice were injected with STZ (ip, 40mg/ kg) daily for 5 consecutive days or with saline (control, C). Normal glycemia (Glyc) is 149±13 mg/dl. Animals with Glyc greater than or equal to 250 mg/dl were considered diabetics and injected with daily IMT doses (20 mg/ kg/ day, sc) for 10 days (STZ-IMT) or saline as control (STZ) (day 1). C mice were injected with the same IMT doses (C-IMT) too. Animals were submitted to another 5 doses of IMT starting on 21 and 36 days. Body weight and glycemia were recorded. At the end of the experiment, glucose tolerance tests (GTT) were performed (2g/ kg BW glucose was injected ip, day 59). IMT treatment induced a marked Glyc decrease, day 66= C: 130±9 vs STZ-IMT: 278±46, p value less to 0.01, STZ-IMT vs STZ: 557±20, p value less to 0.01. GTT showed a partial recovery in the STZ-IMT responsiveness; 0 min= C: 117±11 vs STZ-IMT: 164±9, ns, C vs STZ: 309±53, p value less to 0.05; 30 min= C: 292±51 vs STZ-IMT: 342±33, ns, C vs STZ: 488±36, p value less to 0.05; 120 min C: 133±15 vs STZ-IMT: 352±28, p value less to 0.05, C vs STZ: 472±52, p value less to 0.05. IMT promoted a transient body weight decrease in diabetic animals. IMT504 could improve the diabetic condition in this model of type I diabetes.