No abstract

Administration of pyridoxal 5' phosphate (PLP) has demonstrated beneficial effects in the management of diabetes, albeit the mechanism(s) are not clearly understood. The present study addressed the islet-cell function(s) in streptozotocin (STZ)-induced diabetic mice both in vitro and in vivo. Primary islet cells primed with or without PLP (5 mmol/L) were treated with STZ (2 mmol/L) and were measured for cell viability, insulin secretion, free radicals and mRNA of Insulin and Pdx1. The specificity of PLP's response on insulin secretion was assessed with amino oxy acetic acid (AOAA)-PLP inhibitor. In vivo, the STZ (200 mg/kg b.w)-treated diabetic mice received 10 mmol/L PLP intraperitoneally a day before (PLP + STZ) or after (STZ + PLP) with three more doses once every 48 h. On 7, 14 and 21 d of STZ treatment, physiological parameters, islet morphology, insulin:glucagon, insulin:HSP104, and mRNA of Insulin, Glut2, Pdx1 and Reg1 were determined. In vitro, PLP protected islets against STZ-induced changes in viability, insulin secretion, prevented increase in free radical levels and normalized mRNA of Insulin and Pdx1. Further, AOAA inhibited PLP-induced insulin secretion in islets. In vivo, PLP treatment normalized STZ-induced changes in physiological parameters, circulating levels of PLP and insulin. Also, islet morphology, insulin:glucagon, insulin:HSP104 and mRNA levels of Insulin, Pdx1 and Glut2 were restored by 21 d. Although PLP treatment (pre- and post-STZ) prevented development of frank diabetes, STZ + PLP mice showed transient hyperglycemia, and increased mRNA for Reg1. The data suggest the cytoprotective vis-à-vis insulinotrophic effects of PLP against STZ-induced beta-cell dysfunction and underline its prophylactic use in the management of diabetes.

We report for the first time the immunolocalization of NPC in the pancreas of mice of different ages (3 d to 8 wk) with reference to insulin and glucagon positive cells. The heterogeneous localization of the NPC observed may be of functional and developmental significance and suggest(s) that mice pancreatic tissue can be a potential source of progenitor cells. NPC from the pancreas can be isolated, proliferated and programmed to differentiate into insulin secreting cells under the appropriate microenvironment.