title: Aqueous fraction of Beta vulgaris ameliorates hyperglycemia in diabetic mice due to enhanced glucose stimulated insulin secretion, mediated by acetylcholine and GLP-1, and elevated glucose uptake via increased membrane bound GLUT4 transporters.
abstract: BACKGROUND
  The study was designed to investigate the probable mechanisms of anti-hyperglycemic activity of B. Vulgaris.
  
  
  RESULTS
  Aqueous fraction of B. Vulgaris extract was the only active fraction (50mg/kg). Plasma insulin level was found to be the highest at 30 mins after B. Vulgaris administration at a dose of 200mg/kg. B. Vulgaris treated mice were also assayed for plasma Acetylcholine, Glucagon Like Peptide-1 (GLP-1), Gastric Inhibitory Peptide (GIP), Vasoactive Intestinal Peptide, Pituitary Adenylate Cyclase-Activating Peptide (PACAP), Insulin Like Growth Factor-1 (IGF-1), Pancreatic Polypeptides (PP), and Somatostatin, along with the corresponding insulin levels. Plasma Acetylcholine and GLP-1 significantly increased in B. Vulgaris treated animals and were further studied. Pharmacological enhancers, inhibitors, and antagonists of Acetylcholine and GLP-1 were also administered to the test animals, and corresponding insulin levels were measured. These studies confirmed the role of acetylcholine and GLP-1 in enhanced insulin secretion (p<0.05). Principal signaling molecules were quantified in isolated mice islets for the respective pathways to elucidate their activities. Elevated concentrations of Acetylcholine and GLP-1 in B. Vulgaris treated mice were found to be sufficient to activate the respective pathways for insulin secretion (p<0.05). The amount of membrane bound GLUT1 and GLUT4 transporters were quantified and the subsequent glucose uptake and glycogen synthesis were assayed. We showed that levels of membrane bound GLUT4 transporters, glucose-6-phosphate in skeletal myocytes, activity of glycogen synthase, and level of glycogen deposited in the skeletal muscles all increased (p<0.05).
  
  
  CONCLUSIONS
  Findings of the present study clearly prove the role of Acetylcholine and GLP-1 in the Insulin secreting activity of B. Vulgaris. Increased glucose uptake in the skeletal muscles and subsequent glycogen synthesis may also play a part in the anti-hyperglycemic activity of B. Vulgaris.
authors: Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh.
authors: Ashraf
authors: A
authors: Ul Kabir
authors: Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh.
authors: Mehdi Bin
authors: MB
authors: Samad
authors: Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh.
authors: Arif
authors: A
authors: Ahmed
authors: Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh.
authors: Mohammad Rajib
authors: MR
authors: Jahan
authors: Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh.
authors: Farjana
authors: F
authors: Akhter
authors: Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh.
authors: Jinat
authors: J
authors: Tasnim
authors: Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh.
authors: S M Nageeb
authors: SM
authors: Hasan
authors: Pharmacy Discipline, Life Science School, Khulna University, Khulna, Bangladesh.
authors: Sania Sarker
authors: SS
authors: Sayfe
authors: Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh.
authors: J M A
authors: JM
authors: Hannan
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D027461:Beta vulgaris / Q000737:chemistry*; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice; D032342:Muscle Cells / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D014867:Water / Q000737:chemistry
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D010936:Plant Extracts; D014867:Water; D019298:Glucose-6-Phosphate; D052216:Glucagon-Like Peptide 1; D006003:Glycogen; D006006:Glycogen Synthase; D006593:Hexokinase; D005947:Glucose; D000109:Acetylcholine
references: Diabetes. 2004 Jul;53(7):1714-20
references: 15220195
references: J Ethnopharmacol. 2000 Nov;73(1-2):251-9
references: 11025163
references: Arch Intern Med. 2003 Jun 9;163(11):1306-16
references: 12796066
references: FEBS Lett. 1987 Nov 16;224(1):224-30
references: 2960560
references: Arch Intern Med. 1994 Oct 10;154(19):2169-78
references: 7944837
references: Diabetes Care. 2008 Jan;31 Suppl 1:S61-78
references: 18165339
references: Med Clin North Am. 1998 Jul;82(4):909-29
references: 9706126
references: J Clin Endocrinol Metab. 2002 Mar;87(3):978-82
references: 11889147
references: Endocrinology. 1980 Oct;107(4):1065-8
references: 6105951
references: Diabetes Care. 1995 Feb;18(2):258-68
references: 7729308
references: Cell Metab. 2013 Aug 6;18(2):162-85
references: 23791483
references: Biochem J. 1993 Oct 1;295 ( Pt 1):287-93
references: 8216230
references: J Clin Endocrinol Metab. 1994 Apr;78(4):809A-809F
references: 8157701
references: Am J Hypertens. 1993 Jul;6(7 Pt 2):260S-270S
references: 8398010
references: J Biol Chem. 1961 Feb;236:253-61
references: 13772576
references: Diabetes Care. 1992 Mar;15(3):318-68
references: 1532777
references: Am J Physiol Endocrinol Metab. 2008 Dec;295(6):E1323-32
references: 18812462
references: J Biol Chem. 1965 Feb;240:588-93
references: 14275108
references: Lancet. 1998 Sep 12;352(9131):837-53
references: 9742976
references: Diabetologia. 1993 Aug;36(8):741-4
references: 8405741
references: J Am Diet Assoc. 1995 Sep;95(9):1009-17
references: 7657902
references: J Clin Invest. 1984 Oct;74(4):1515-25
references: 6148358
references: Diabetologia. 1973 Dec;9(6):439-46
references: 4589822
references: Physiol Res. 2001;50(6):537-46
references: 11829314
references: FASEB J. 1997 Jun;11(7):544-58
references: 9212078
references: J Clin Invest. 1987 Feb;79(2):616-9
references: 3543057
references: Diabetologia. 1991 Oct;34(10):763-5
references: 1959709
references: Diabetes. 2000 Nov;49(11):1751-60
references: 11078440
references: JAMA. 2006 Apr 12;295(14):1681-7
references: 16609090
references: J Med Food. 2002 Spring;5(1):37-42
references: 12511111
references: Diabetes Care. 2002 Mar;25(3):608-13
references: 11874956
references: Nat Med. 2000 Aug;6(8):924-8
references: 10932232
references: N Engl J Med. 2010 Mar 4;362(9):774-7
references: 20164475
references: Nat Protoc. 2009;4(11):1649-52
references: 19876025
references: Metabolism. 1979 Apr;28(4):373-86
references: 36543
references: Diabetes Care. 1997 Sep;20(9):1353-6
references: 9283777
references: Gastroenterology. 2007 May;132(6):2131-57
references: 17498508
references: Phytother Res. 2002 Dec;16(8):758-61
references: 12458482
references: Diabetes Care. 1990 Jun;13(6):655-66
references: 2192849
references: Am J Physiol. 1988 Dec;255(6 Pt 1):E769-74
references: 3059816
references: J Clin Invest. 1995 Dec;96(6):2792-801
references: 8675649
references: Diabetes Care. 2007 Jun;30(6):1608-10
references: 17372153
references: Arch Intern Med. 1998 May 11;158(9):998-1004
references: 9588433
references: Diabetologia. 2004 Mar;47(3):478-487
references: 14762654
references: J Clin Invest. 1967 Jan;46(1):86-94
references: 6018752
references: Physiologist. 1996 Aug;39(4):199, 208-11
references: 8854724
references: Ann Intern Med. 2007 Sep 18;147(6):386-99
references: 17638715
references: Physiol Rev. 1987 Oct;67(4):1185-248
references: 2825225
references: Br J Nutr. 2012 May;107(9):1316-23
references: 21899804
references: Am J Physiol. 1989 Sep;257(3 Pt 1):G397-401
references: 2551182