Effects of surface camouflaged islet transplantation on pathophysiological progression in a db/db type 2 diabetic mouse model

Biochem Biophys Res Commun. 2013 Apr 19;433(4):513-8. doi: 10.1016/j.bbrc.2013.03.015. Epub 2013 Mar 21.

Abstract

To investigate the inhibition effects of pancreatic islet transplantation on the progression of obese type 2 diabetes, we analyzed the effects of surface camouflaged islet transplantation on delaying the disease progression in a db/db diabetic mouse model. Surface camouflaged islets using 6-arm-PEG-catechol were transplanted in db/db diabetic mice. The fat accumulation and toxicity in the liver, the expansion of islets in the pancreas, and the size change of abdominal adipocyte were analyzed. In addition, the blood glucose control, insulin levels and immunohistochemical staining of recovered tissues were analyzed after transplantation. Then co-administration of anti-CD154 monoclonal antibody and Tacrolimus (IT group) deterred the pathophysiological progression of obese type 2 diabetes. At day 3 of transplantation, the serum insulin concentration of IT group was increased compared to the db/db diabetic mice group. The immunohistochemical studies demonstrated that the mass of 6-arm-PEG-catechol grafted islet was preserved in the transplantation site for 14 days. Surface modification using 6-arm-PEG-catechol effectively inhibited the immune cell infiltration and activation of host immune cells when immunosuppressive drug was given to the db/db type 2 diabetes mice. Therefore, 6-arm-PEG-catechol grafted islets effectively restored the insulin secretion in islet recipients and prevented the disease progression in type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology
  • Blood Glucose
  • CD40 Ligand / administration & dosage
  • CD40 Ligand / immunology
  • Catechols / chemical synthesis
  • Catechols / metabolism
  • Cell Shape
  • Cell Size
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetes Mellitus, Experimental / therapy
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetes Mellitus, Type 2 / therapy
  • Disease Progression
  • Immunohistochemistry
  • Insulin / metabolism*
  • Insulin Resistance
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans Transplantation / methods*
  • Liver / metabolism
  • Liver / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tacrolimus / administration & dosage
  • Tacrolimus / immunology
  • Time Factors
  • Transplantation, Heterologous

Substances

  • Antibodies, Monoclonal
  • Blood Glucose
  • Catechols
  • Insulin
  • CD40 Ligand
  • Polyethylene Glycols
  • catechol
  • Tacrolimus