title: Cycloart-23-ene-3β, 25-diol stimulates GLP-1 (7-36) amide secretion in streptozotocin-nicotinamide induced diabetic Sprague Dawley rats: a mechanistic approach.
abstract: In previous study, we have reported cycloart-23-ene-3β, 25-diol is an active antidiabetic constituent isolated from stem bark of Pongamia pinnata (Linn.) Pierre. The objective of the present investigation was to evaluate cycloart-23-ene-3β, 25-diol stimulates glucagon like peptide-1 (GLP-1) (7-36) amide secretion in streptozotocin-nicotinamide induced diabetic Sprague Dawley rats. Molecular docking studies were performed to elucidate the molecular basis for GLP-1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100mg/kg, i.p.) followed by administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into following groups; I- non-diabetic, II- diabetic control, III- sitagliptin (5mg/kg, p.o.), IV- cycloart-23-ene-3β, 25-diol (1mg/kg, p.o.). The cycloart-23-ene-3β, 25-diol and sitagliptin treatment was 8 week. Plasma glucose was estimated every week (week 0 to week 8). Body weight, food and water intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, mRNA expression of proglucagnon GLP-1, plasma and pancreatic insulin, histology of pancreata as well as biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8th week treatment. In acute study, active GLP-1 (7-36) amide release, plasma glucose and insulin were measured during oral glucose tolerance test. The docking data clearly indicated cycloart-23-ene-3β, 25-diol bind to the GLP-1 receptor. It decreased plasma glucose level, increased plasma and pancreatic insulin level as well as increased plasma and colonic active GLP-1 (7-36) amide secretion in streptozotocin-nicotinamide induced diabetic Sprague Dawley rats.
authors.affiliation: Department of Pharmacology, PES's Modern College of Pharmacy, Sector 21, Yamuna Nagar, Nigadi, Pune 411044, India. sachinbadole@rediffmail.com
authors.forename: Sachin L
authors.initials: SL
authors.lastname: Badole
authors.forename: Sagar P
authors.initials: SP
authors.lastname: Mahamuni
authors.forename: Pranita P
authors.initials: PP
authors.lastname: Bagul
authors.forename: Rekha D
authors.initials: RD
authors.lastname: Khose
authors.forename: Anuja C
authors.initials: AC
authors.lastname: Joshi
authors.forename: Arvindkumar E
authors.initials: AE
authors.lastname: Ghule
authors.forename: Subhash L
authors.initials: SL
authors.lastname: Bodhankar
authors.forename: Chandrashekhar G
authors.initials: CG
authors.lastname: Raut
authors.forename: Vijay M
authors.initials: VM
authors.lastname: Khedkar
authors.forename: Evans C
authors.initials: EC
authors.lastname: Coutinho
authors.forename: Nilesh K
authors.initials: NK
authors.lastname: Wagh
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004326:Drinking / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008297:Male; D062105:Molecular Docking Simulation; D009536:Niacinamide / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011719:Pyrazines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068900:Sitagliptin Phosphate; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D014315:Triterpenes / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C102764:9,19-cycloart-23-ene-3,25-diol; D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D011719:Pyrazines; D014230:Triazoles; D014315:Triterpenes; C055453:glucagon-like peptide 1 (7-36)amide; D009536:Niacinamide; D052216:Glucagon-Like Peptide 1; D000068900:Sitagliptin Phosphate