The effect of a heparin analogue, ITF-5005, on diabetes incidence and insulitis in the non-obese diabetic mouse.
It has been suggested that heparin and its analogues may have a suppressive effect on the immune response by interfering with T-lymphocyte heparinase activity, thus altering the ability of T-lymphocytes to penetrate the extracellular matrix and migrate to target tissues. We have investigated whether a heparin analogue (ITF-5005) can alter lymphocytic infiltration of the endocrine pancreas (insulitis) and/or diabetes incidence in the non-obese diabetic (NOD) mouse. Sixty-four NOD mice were divided at weaning and injected subcutaneously five times per week with either 18, 36 or 72 micrograms/kg body weight of ITF-5005 or saline as a control. At 12 weeks of age, the animals were culled and their pancreata sectioned, stained and assessed 'blind' for insulitis and insulin containing cells. Insulitis was similar in all groups as was the proportion of insulin-containing cells. To determine the effect on diabetes incidence, two groups of mice were injected with either saline or 140 micrograms/kg body weight of ITF-5005 from weaning until 30 weeks of age. No 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 the proportion of treated group. We conclude that ITF-5005, at the doses employed, has no effect on insulitis or the proportion of insulin-containing cells found in the pancreas, but that it can accelerate the course of diabetes in the NOD mouse.
Beales
P E
PE
Department of Diabetes and Metabolism, St. Bartholomew's Hospital, West Smithfield, London, UK.
Williams
A J
AJ
Signore
A
A
Procaccini
E
E
Xu
S
S
Pozzilli
P
P
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology; D007279:Injections, Subcutaneous; D007515:Islets of Langerhans / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD / Q000502:physiology*; D010182:Pancreatic Diseases / Q000473:pathology*
C084655:ITF 5005; D006493:Heparin