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The heterogeneity of microvascular endothelial cells derived from different organs, suggests that these cells have specialised functions at different anatomical sites. The microvasculature is, in fact, a key interface between blood and tissues and participates in numerous pathophysiological processes. Pancreatic islet microcirculation exhibits distinctive features, in an interdependent physical and functional relationship with ┚ cells, from organogenesis to adult life. The islet microendothelium behaves as an active “gatekeeper” in the control of leukocyte recruitment into the islets during autoimmune insulitis in type 1 diabetes. Furthermore, microvascular endothelial cells, forming the key lining between the vascular space and organ parenchyma, have been shown to influence organ and tissue specific susceptibility to viral infection, and to modulate the pathological expression of virusinduced diseases, which potentially includes type 1 diabetes. Endothelial cells expressing appropriate receptors would fail to act as effective barrier to infections, allowing viral particles to pass through, and replicate in, the vascular endothelium. Human Enteroviruses (EV), especially those of the Coxsackievirus B (CVB) group, are associated with a wide variety of clinical syndromes and have long been considered possible culprits of inflammatory conditions and immune-mediated pathological processes, such as chronic dilated cardiomyopathy, chronic myositis and type 1 diabetes mellitus (Rose et al., 1993; Luppi et al., 1998; Hyoty & Taylor, 2002). Several mechanisms, including molecular mimicry, bystander activation of autoreactive T cells, superantigenic activity of viral proteins, not mutually exclusive, have been proposed to explain the relationship between EV infections and induction of autoimmune diseases (Varela-Calvino & Peakman, 2003; Horwitz et al., 1998; Wucherpfennig, 2001). Evidences of a link between viral infections and initiation or acceleration of pancreatic islet autoimmunity have been under investigation for almost 30 years, and EVs, especially those of the Coxsackievirus B (CVB) group, are historically the prime suspects as important aetiological determinants in type 1 diabetes (Hyoty & Taylor, 2002; Varela-Calvino & Peakman, 2003). Endothelial cells derived from different organs show distinct susceptibility to CVB infections, and the behaviour against a viral challenge of endothelial cells in large vessels and microvessels may differ (Friedman et al. 1981; Huber et al., 1990; Conaldi et al. 1997; Zanone et al., 2003; Saijets et al., 2003).

Type 1 diabetes is an autoimmune disease leading to the destruction of pancreatic cells. The reduction of cell mass results in insulin deficiency that leads to a failure of glucose homeostasis with increased levels of glucose in blood. Hyperglycemia which per se is detrimental for the organism and may be life-threatening, may in the long term associate with chronic complications involving blood vessels and nerves. The gold standard treatment for diabetes patients aimed to reach a tight control of glycemia, relies on intensive insulin therapy based on multiple daily injections or continuous subcutaneous infusion of insulin. A tight control of glycemia reached with such regimens was shown to significantly reduce the incidence of microvascular complications in respect to the conventional insulin therapy. Nevertheless, to reach an optimal control of blood levels may prove to be difficult when compared to the physiological condition where this is guaranteed by the pancreatic  cells (Suckale, 2008). Therefore, preservation of cell mass could be an important therapeutic target to reduce microvascular complications and to improve the glycemia control (Gonez & Knight, 2010). It is generally accepted that the endocrine pancreas has some regenerative capabilities, although it is still debated which cells are involved in cell turnover. In rodents the capability of adult pancreas to increase cell mass has been documented in physiological conditions and after injury. The understanding of mechanisms involved in  cell turnover may therefore be relevant to design new therapeutic strategies aimed to maintain a  cell mass or to favour regeneration of  cells. These strategies however, should take to account the problem of recurrent autoimmunity that in type 1 diabetes not only impairs the original cell mass, but may also limit the regenerative process. Indeed, autoimmune T lymphocytes may kill the cells newly formed in response to injury (Fan & Rudert, 2009).