title: Pyridoxal 5' phosphate protects islets against streptozotocin-induced beta-cell dysfunction--in vitro and in vivo.
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.
authors.affiliation: Department of Biochemistry/Stem Cell Research, National Institute of Nutrition (ICMR, Department of Health Research), Hyderabad 500007, India.
authors.forename: Sashi G
authors.initials: SG
authors.lastname: Kiran
authors.forename: Raj K
authors.initials: RK
authors.lastname: Dorisetty
authors.forename: Malathi R
authors.initials: MR
authors.lastname: Umrani
authors.forename: Sesikeran
authors.initials: S
authors.lastname: Boindala
authors.forename: Ramesh R
authors.initials: RR
authors.lastname: Bhonde
authors.forename: Maniprabha
authors.initials: M
authors.lastname: Chalsani
authors.forename: Himadri
authors.initials: H
authors.lastname: Singh
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Venkatesan
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin
chemical_list: D017931:DNA Primers; D007328:Insulin; D011732:Pyridoxal Phosphate; D013311:Streptozocin