THE EFFECT OF A HEPARIN ANALOG, ITF-5005, ON DIABETES INCIDENCE AND INSULITIS IN THE NONOBESE DIABETIC MOUSE

It has been suggested that heparin and its analogues may have a suppre ssive effect on the immune response by interfering with T-lymphocyte h eparinase activity, thus altering the ability of T-lymphocytes to pene trate the extracellular matrix and migrate to target tissues. We have investigated whether a heparin analogue (ITF-5005) can alter lymphocyt ic infiltration of the endocrine pancreas (insulitis) and/or diabetes incidence in the non-obese diabetic (NOD) mouse. Sixty-four NOD mice w ere divided at weaning and injected subcutaneously five times per week with either 18, 36 or 72 mug/kg body weight of ITF-5005 or saline as a control. At 12 weeks of age, the animals were culled and their pancr eata sectioned, stained and assessed 'blind' for insulitis and insulin containing cells. Insulitis was similar in all groups as was the prop ortion of insulin-containing cells. To determine the effect on diabete s incidence, two groups of mice were injected with either saline or 14 0 mug/kg body weight of ITF-5005 from weaning until 30 weeks of age. N o difference was found in overall diabetes incidence; however, disease onset was significantly accelerated in the treated group. We conclude that ITF-5005, at the doses employed, has no effect on insulitis or t he proportion of insulin-containing cells found in the pancreas, but t hat it can accelerate the course of diabetes in the NOD mouse.