VAMP8 Deletion Delays the Onset of Streptozotocin-Induced Hyperglycemia

Abstract

ObjectiveWe recently reported that vesicle-associated membrane protein (VAMP) isoform 8 deletion increased islet β-cell mass. We now sought to determine if VAMP8 deletion-induced increase in islet β-cell mass would provide protection against streptozotocin (STZ)-induced β-cell destruction, and subsequently alleviate STZ-induced diabetes. MethodsVAMP8 null mice (KO) and age-matched littermate controls (WT) were treated with single daily intraperitoneal injections of STZ (40 mg/kg body weight) for 5 consecutive days. Intraperitoneal glucose (2 g/kg body weight) tolerance tests were carried out to determine blood glucose and insulin levels. Pancreas samples were obtained for histological assessment of β-cell mass (β-cell area per pancreatic area), proliferative (Ki67) and apoptotic (TUNEL) activities. ResultsSTZ-treated VAMP8 KO mice compared to WT mice displayed delayed onset in hyperglycemia, superior glucose tolerance and higher plasma insulin levels. However, the number of TUNEL-positive cells was similar between WT and VAMP8 KO islets. The number of Ki67-positive cells and the ratio of β-cell area per pancreatic area showed a higher but insignificant trend in VAMP8 KO mice islets vs. WT mice islets. ConclusionsVAMP8 deletion did not appear to protect against β-cell destruction by STZ; nonetheless, the residual increase in basal β-cell mass attributed to enhanced glucose tolerance and delayed onset of hyperglycemia.