title: Trigonelline and vildagliptin antidiabetic effect: improvement of insulin signalling pathway.
abstract: OBJECTIVE
  Trigonelline (TRG) is known to have an antidiabetic efficacy; however, its mechanism is not entirely elucidated.
  
  
  METHODS
  Hence, its effect on insulin signaling, besides its effectiveness in combination with vildagliptin (VLD) in a Type 2 diabetes model has been tested.
  
  
  RESULTS
  TRG (50 mg/kg; p.o) lowered serum glucose, fructosamine, insulin, and HOMA-IR index and increased insulin sensitivity in soleus muscle via augmenting insulin receptor autophosphorylation (IR-PH), pT308-Akt, and glucose transporter 4 (GLUT4). Additionally, it reduced muscle advanced glycation end products and lipid peroxides with increased glutathione. TRG showed an anti-lipidemic effect lowering serum and/or muscle total cholesterol, triglycerides, and FFAs to decrease body weight, and visceral/epididymal indices. Furthermore, VLD (3 and 10 mg/kg, p.o) increased IR-PH, pT308-Akt, and GLUT4 to improve insulin signaling. The combined effect of TRG with the low dose of VLD was mostly confined to the reduction of the aberrant lipid profile.
  
  
  CONCLUSIONS
  The beneficial effect of TRG on insulin sensitivity and glucose/ lipid homeostasis is mediated by the enhancement of the insulin signaling and antioxidant property. Moreover, the positive impact of VLD on pT308-Akt is an integral part in insulin signaling, and hence its antidiabetic effect.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Amat-Alrazaq A
authors.initials: AA
authors.lastname: Aldakinah
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Muhammad Y
authors.identifier: http://orcid.org/0000-0002-5104-6821
authors.initials: MY
authors.lastname: Al-Shorbagy
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Dalaal M
authors.initials: DM
authors.lastname: Abdallah
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Hanan S
authors.initials: HS
authors.lastname: El-Abhar
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077597:Vildagliptin
chemical_list: D000470:Alkaloids; D000975:Antioxidants; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D008055:Lipids; D009570:Nitriles; D011759:Pyrrolidines; C009560:trigonelline; D011972:Receptor, Insulin; D000077597:Vildagliptin; D000218:Adamantane
keywords: glucose transporter 4; insulin receptor autophosphorylation; lipid homoeostasis; pT308-Akt