EXPRESSION OF VMP1 PRECEDES PANCREATIC BETA CELL DEATH IN EXPERIMENTAL DIABETES.

VACCARO MI; GRASSO D; ROPOLO A; PARDO R; GONZALEZ CD; IOVANNA JL

Chicago, IL, USA.

Congreso; 34th Annual Meeting of the American Pancreatic Association; 2003

American Pancreatic Association

Type I diabetes is an autoimmune disease that results in destructive depletion of the insulin-producing beta cells in the islets of Langerhans in pancreas. Recently, we described the cloning of the VMP1 (Vacuole Membrane Protein 1). This new gene codes for a transmembrane protein located to the Golgi apparatus and the endoplasmic reticulum area. In vitro expression of VMP1 gene promotes formation of intracellular vacuoles followed by cell death. In order to test if VMP1 expression is implicated in pancreatic B cell destruction during experimental diabetes, male wistar rats were given a single intravenous injection of 60 mg. kg (-1) body weight streptozotocin, and were sacrificed at different time intervals up to 48 h following the treatment. Their pancreas were excised and randomly processed for in situ hybridization, immunohistochemistry and electron microscopic examination. Hyperglycemia and glucosuria were detected 12 h after treatment, became remarkably high at 24 h and persisted thereafter. In situ hybridization of the islets of Langerhans from treated rats showed high expression of VMP1 in the central B cells during the first 24 h of treatment. Light microscopic examination of thin plastic sections revealed an early chromatin aggregation and cytoplasm vacuolization after the same time of streptozotocin treatment. Lysis of B cells occurred 48 h after treatment with marked infiltration and VMP1 was still expressed by the remaining B cells. No expression of VMP1 was observed in A and D cells at the margin of the islets and their morphology looked perfectly unaltered. Our results indicated that VMP1 expression precedes pancreatic beta cell death and may be implicated in the cytoplasm vacuolization early after streptozotocin treatment, suggesting that VMP1 expression is involved in the destruction process of pancreatic beta cells during type I diabetes.