Type 1 (insulin-dependent) diabetes mellitus is an autoimmune disease characterized by the failure to synthesize or secrete insulin, and diabetics are likely to suffer complications that include kidney and heart disease, as well as loss of sight, angiopathy, tissue hypoxia, reduction in organ blood flow, impaired wound healing, respiratory infections, arteriosclerosis, etc., thus diabetes very closely resembles a state of chronic hypoxia. It is now well recognized that hypoxia is an important environmental stimulus capable of modulating the expression of many genes involved in energy metabolism. The diabetic metabolic stress resulting from impaired energy metabolism, which produce altered production of inflammatory mediators, may increase the risk of oxidative injury. The aim was to investigate whether production of MIP-2 and MCP-1 are implicated in the pathogenesis of diabetes, and if the regulatory effects of these chemokines are affected by hypoxia. Two groups of rats, diabetic and non-diabetic, were kept in normoxic room air conditions or subjected to chronic hypoxia. Expression and production of chemokines were measured by RT-PCR and ELISA assay. In diabetic rats, we found a marked increase of MCP-1 when compared with non-diabetic rats (783.5+/- 49 versus 461.9 +/- 27), while no significant differences were detected for MIP-2 levels. Hypoxia selectively modulated chemokines production, since MCP-1 expression and production was up-regulated in the diabetic groups (783.5+/- 49 versus 461.9+/- 27), but down-regulated MIP-2 expression and production (87.8+/- 23 versus 522.1+/- 72). Our data point to MCP-1 and MIP-2 as important components in the pathophysiology of diabetes, and hypoxia is an important and potent environmental stimulus capable of modulating the expression and production of these chemokines.
(Mol Cell Biochem 276: 105-111, 2005).