Islet neogenesis-associated protein-related pentadecapeptide improves the function of allograft after islets transplantation

J Pediatr Endocrinol Metab. 2014 Nov;27(11-12):1167-73. doi: 10.1515/jpem-2014-0127.

Abstract

Objective: To investigate the protective effects of a pentadecapeptide of islet neogenesis-associated protein (INGAP-PP) on transplanted islets function.

Methods: Islets were cultured in RPMI 1640 with or without INGAP-PP (10 μg/mL). After 24 h, the viability of the islets and glucose-stimulated insulin secretion (GSIS) were measured. The expression of genes B cell lymphoma/lewkmia2 (Bcl2) and protein kinase B (Akt) were detected by RT-PCR assay. Healthy rats transplanted with islets under the renal capsule were injected with INGAP-PP or saline in in the abdominal cavity. One week later, the expression of insulin nestin pancreatic (nestin) and duodenal homeobox 1 (Pdx1) and proliferating cell nuclear antigen (PCNA) in the transplanted islets were observed by immunohistochemistry. After that they were transplanted to the renal capsule of diabetic rats.

Results: 1. The amount of insulin released was increased in co-cultured group in concentration of 16.7 mmol/L glucose, which was (185.00±20.01 μU/mL) vs. (58.67±17.03 μU/mL). Gene expression of Bcl2 (0.61±0.22 vs. 0.50±0.21) and Akt (1.12±0.19 vs. 0.94±0.16) in the co-cultured group were increased compared with that of the control group. Islets viability in the co-cultured group (683.9±7.08) was higher than that of control group (547.9±8.02). The stimulating index (SI) of the co-cultured group was also higher than that of the control group. 2. The group of islets under the renal capsule which were co-cultured and injected with INGAP-PP had the more nestin expression in the islets.

Conclusions: The function of islet can be protected by the INGAP-PP, which will promote the viability, differentiation and regeneration of islet before transplantation. And it will be beneficial for the function of allograft after islets transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts
  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cytokines / pharmacology*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / prevention & control*
  • Glucose / pharmacology
  • Graft Survival / physiology*
  • Immunoenzyme Techniques
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans Transplantation*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Pancreatitis-Associated Proteins
  • Peptide Fragments / pharmacology*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cytokines
  • INGAP peptide
  • Insulin
  • Lectins, C-Type
  • Pancreatitis-Associated Proteins
  • Peptide Fragments
  • REG3A protein, human
  • RNA, Messenger
  • Reg3b protein, rat
  • Glucose