Effect of combined therapy of human Wharton's jelly-derived mesenchymal stem cells from umbilical cord with sitagliptin in type 2 diabetic rats

Endocrine. 2014 Mar;45(2):279-87. doi: 10.1007/s12020-013-9984-0. Epub 2013 May 18.

Abstract

Type 2 diabetes mellitus is the most common endocrine disease all over the world, while existing therapies can only ameliorate hyperglycemia or temporarily improve the response to insulin in target tissues, they cannot retard or improve the progressive β-cell dysfunction persistently. Combined therapy of stem cells and sitagliptin might resolve this problem, we verified this hypothesis in a diabetic rat model. Except ten Wistar rats in normal control group, diabetic rats were divided into diabetic control group, WJ-MSCs group, sitagliptin group and WJ-MSCs + sitagliptin group and received homologous therapy. Ten weeks after therapy, diabetic symptoms, FPG and GHbA1c in WJ-MSCs group, sitagliptin group and WJ-MSCs + sitagliptin group were significantly less than those in diabetic control group (P < 0.05), while fasting C-peptide and number of β cells in WJ-MSCs group and WJ-MSCs + sitagliptin group was significantly higher than those in diabetic control and sitagliptin group (P < 0.01). Glucagon and number of α cells in sitagliptin group and WJ-MSCs + sitagliptin group were significantly lower than those in WJ-MSCs group and diabetic control group (P < 0.01). No symptoms of rejection and toxic effect were observed. Combined therapy of WJ-MSCs and sitagliptin can effectively ameliorate hyperglycemia, promote regeneration of islet β cells and suppress generation of islet α cells in diabetic rats, presenting a new therapy for type 2 diabetes although the exact mechanisms are unclear.

MeSH terms

  • Animals
  • C-Peptide / metabolism
  • Cell Proliferation / drug effects
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / therapy*
  • Disease Models, Animal
  • Glucagon / metabolism
  • Glycated Hemoglobin / metabolism
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / metabolism
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use*
  • Rats
  • Rats, Wistar
  • Sitagliptin Phosphate
  • Streptozocin / adverse effects
  • Treatment Outcome
  • Triazoles / pharmacology
  • Triazoles / therapeutic use*
  • Umbilical Cord / cytology

Substances

  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Pyrazines
  • Triazoles
  • Streptozocin
  • Glucagon
  • Sitagliptin Phosphate