ABSTRACT
<p><b>OBJECTIVE</b>To study the effect of Astragalus polysaccharide (APS) on pancreatic beta cell mass in type 1 diabetic mice.</p><p><b>METHOD</b>Diabetic mice induced by multiple low dose streptozotocin (MLD-STZ) were administered either APS (100, 200, 400 mg x kg(-1) body weight) or saline intraperitoneally daily, and sacrificed after 15 or 30 days of treatment. Streptavidin-peroxidase immunohistochemical method with counterstain was performed to determine the effect of APS on insulitis. Indirect double immunofluorescence for Insulin/Ki67 (counterstained by Hoechst33258) and Insulin/Cleaved caspase-3 was used to evaluate pancreatic cell (besides beta cell) proliferation, beta cell neogenesis, beta cell apoptosis and beta cell mass. Semi-quantitative RT-PCR was utilized to characterize pancreatic regenerating protein 1 mRNA levels, and ELISA method was performed to measure the levels of cytokine IFN-gamma and IL-4 secreted by splenocytes.</p><p><b>RESULT</b>Attenuated insulitis, upregulated beta cell mass, increased number of neogenetic pancreas islets, decreased number of apoptosis beta cells and downregulation of Th1/Th2 cytokine ratio were significantly time-and dose-dependent on APS treatment, when compared to saline controls. However, no significant differences of the number of pancreatic proliferative cells or replicative cells and pancreatic regenerating protein 1 mRNA levels were demonstrated between APS (APS100, APS200 and APS400) and saline vehicle group on day 15 and 30 with APS treatment.</p><p><b>CONCLUSION</b>APS can upregulate pancreatic beta cell mass in type 1 diabetic mice, strongly associated with improved autoimmunity.</p>