title: Improved outcome of islet transplantation in partially pancreatectomized diabetic mice by inhibition of dipeptidyl peptidase-4 with sitagliptin.
abstract: OBJECTIVE
  Glucagon-like peptide-1 (GLP-1) is known to promote beta cell proliferation, and dipeptidyl peptidase-4 (DPP-4) inhibitor increases GLP-1 levels by preventing its degradation. This study was designed to evaluate the effects of sitagliptin (sita), a DPP-4 inhibitor, on the outcome of islet transplantation (ITx) in diabetic mice after partial pancreatectomy (Px).
  
  
  METHODS
  A diabetic mouse model was prepared by performing 70% Px in C57BL/6 mice. The diabetic mice were treated with sita, subjected to ITx, or both treated with sita and subjected to ITx. After 12 days of sita treatment, the pancreatic remnants and transplanted islets were histologically examined.
  
  
  RESULTS
  Dipeptidyl peptidase-4 inhibitor increased the concentration of plasma active GLP-1 regardless of ITx and improved glycemic control in the ITx group. The beta cell mass of the pancreatic remnants increased in the ITx group, and mice that received combined treatment with ITx and sita showed a greater increase in the beta cell mass. Dipeptidyl peptidase-4 inhibitor seems to induce proliferation and inhibit apoptosis of beta cells in pancreatic remnants.
  
  
  CONCLUSIONS
  The DPP-4 inhibitor favorably affects ITx in partially pancreatectomized diabetic mice by increasing the beta cell mass through cell proliferation and inhibition of beta cell apoptosis.
authors: Department of Molecular Medicine, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Young-Seok
authors: YS
authors: Kim
authors: Seung-Hoon
authors: SH
authors: Oh
authors: Ki-Soo
authors: KS
authors: Park
authors: Heesung
authors: H
authors: No
authors: Bae-Jun
authors: BJ
authors: Oh
authors: Soo Kyoung
authors: SK
authors: Kim
authors: Hye Seung
authors: HS
authors: Jung
authors: Jae-Hyeon
authors: JH
authors: Kim
authors: Myung-Shik
authors: MS
authors: Lee
authors: Moon-Kyu
authors: MK
authors: Lee
authors: Kwang-Won
authors: KW
authors: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000628:therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D050417:Insulin-Secreting Cells / Q000473:pathology / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000379:methods* / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010180:Pancreatectomy; D011719:Pyrazines / Q000494:pharmacology*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011719:Pyrazines; D014230:Triazoles; D052216:Glucagon-Like Peptide 1; D000068900:Sitagliptin Phosphate