INSULITIS AND ISLET MICROVASCULATURE IN TYPE-1 DIABETES

Type 1 diabetes is characterized by a mononuclear infiltration, common ly called <<insulitis>>. The cells that constitute the insulitis are m ainly monocytes that are recruited from extraislet areas and arrive at the islet site via the vascular system. Infiltrating cells must then pass across the endothelia to gain access to the islet parenchyma. The anatomy and physiology of the islet microvasculature shows that islet B cells are firstly perfused and influence both endocrine non-B islet cells and peri-insular exocrine cells. The low dose streptozocin (LDS ) treatment is able to induce, other than a monocyte/macrophage recrui tment and activation, islet vascular alterations, mainly at the level of post-capillary venules encircling the islets of Langerhans and a co ncomitant fall in Superoxide-dismutase (SOD) (the first cellular defen ce against free radicals) activity. These findings, together with the increase in vascular permeability and the morphological evidence of ar eas of oedema formation within the islets, have raised the interest in the <<microvascular>> approach to this disease. Actually the reductio n in B-cell perfusion and the concomitant attack by phagocytes with a fall in SOD activity should be considered as events that are linked to each other. On the other hand both macrophages and endothelia are abl e to produce free radicals and, in particular, nitric oxide. This conf irms that the islet vascular system seems to be involved in early insu litis and B-cell lysis.