title: Combination of Sitagliptin and Insulin against Type 2 Diabetes Mellitus with Neuropathy in Rats: Neuroprotection and Role of Oxidative and Inflammation Stress.
abstract: OBJECTIVE
  The present study evaluated the effects of sitagliptin-insulin against type 2 diabetes mellitus with neuropathy in rats and possible neuroprotective mechanisms.
  
  
  METHODS
  Diabetes was induced in 32 adult male albino rats by 6-week high-fat high-sugar diet followed by streptozotocin 30 mg/kg intraperitoneal injection. For 4 weeks thereafter, diabetic rats were divided into 4 groups, each group receiving one of the following daily: vehicle (untreated diabetic), insulin 10 IU/kg SC, sitagliptin 30 mg/kg PO or sitagliptin-insulin. We assessed systolic blood pressure (SBP), blood glucose, serum insulin and advanced glycation end-products (AGEs), thermal hyperalgesia and sciatic nerve tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) and sciatic histopathology.
  
  
  RESULTS
  Compared to untreated and insulin-treated groups, sitagliptin decreased SBP, serum AGEs and sciatic MDA and TNF-α, and increased serum insulin and sciatic SOD, but insulin decreased blood glucose more. Sitagliptin-insulin (greater than sitagliptin or insulin alone) superiorly decreased and increased the above respective parameters, and ameliorated hyperalgesia and sciatic histopathological changes, but was similar to insulin in decreasing blood glucose, and similar to sitagliptin in rising serum insulin.
  
  
  CONCLUSIONS
  Sitagliptin-insulin combination produced hypoglycemic and neuroprotective effect and ameliorated hyperalgesia, oxidative stress and inflammation more than either drug alone. This combination might have clinical efficacy in uncontrolled type 2 diabetes with neuropathy.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia.
authors.forename: Mohamed Elsayed
authors.initials: ME
authors.lastname: Kelany
authors.forename: Tahir M
authors.initials: TM
authors.lastname: Hakami
authors.forename: Adel H
authors.initials: AH
authors.lastname: Omar
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Abdallah
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D003929:Diabetic Neuropathies / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004359:Drug Therapy, Combination; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D000066829:Neuroprotection / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D000068900:Sitagliptin Phosphate