Vildagliptin/pioglitazone combination improved the overall glycemic control in type I diabetic rats

Can J Physiol Pharmacol. 2018 Aug;96(8):710-718. doi: 10.1139/cjpp-2017-0680. Epub 2018 Mar 6.

Abstract

Type I diabetes (TID) is generally assumed to be caused by an immune associated, if not directly immune-mediated, destruction of pancreatic β-cells. In patients with long-term diabetes, the pancreas lacks insulin-producing cells and the residual β-cells are unable to regenerate. Patients with TID are subjected to a lifelong insulin therapy which shows risks of hypoglycemia, suboptimal control and ketosis. In this study, we investigated the potential role of vildagliptin (Vilda) alone or in combination with pioglitazone (Pio), as treatment regimens for TID using streptozotocin (STZ)-induced TID model in rats. Daily oral administration of Vilda (5 mg/kg) alone or in combination with Pio (20 mg/kg) for 7 weeks significantly reduced blood glucose levels and HbA1c. It increased serum insulin levels and decreased serum glucagon. It also showed a strong antioxidant activity. Immunohistochemical analysis showed a marked improvement in β-cells in treated groups when compared with the diabetic group, which appeared in the normal cellular and architecture restoration of β-cells in the islets of Langerhans. Vilda alone or in combination with Pio has the ability to improve the overall glycemic control in type I diabetic rats and may be considered a hopeful and effective remedy for TID.

Keywords: cellule β; diabète sucré de type 1; pioglitazone; regeneration; régénérescence; type I DM; vildagliptin; vildagliptine; β-cell.

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / pathology
  • Drug Therapy, Combination
  • Glucagon / blood
  • Glutathione / metabolism
  • Glycated Hemoglobin / metabolism
  • Insulin / blood
  • Male
  • Malondialdehyde / metabolism
  • Nitric Oxide / metabolism
  • Nitriles / therapeutic use*
  • Pancreas / enzymology
  • Pancreas / pathology
  • Pioglitazone
  • Pyrrolidines / therapeutic use*
  • Rats, Sprague-Dawley
  • Streptozocin
  • Superoxide Dismutase / metabolism
  • Thiazolidinediones / therapeutic use*
  • Vildagliptin

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Nitriles
  • Pyrrolidines
  • Thiazolidinediones
  • Nitric Oxide
  • Malondialdehyde
  • Streptozocin
  • Glucagon
  • Superoxide Dismutase
  • Glutathione
  • Vildagliptin
  • Adamantane
  • Pioglitazone