Islet cell function in long-term surviving primates after segmental pancreatic allotransplantation

Area of Science:

• Transplantation immunology
• Endocrinology
• Surgical research

Background:

• Assessing islet cell function in pancreatectomized primates with pancreatic allografts is crucial for understanding graft viability.
• Immunosuppression protocols involving total lymphoid irradiation (TL1) and cyclosporine (CSA) are standard in pancreatic transplantation.

Purpose of the Study:

• To evaluate islet cell function in pancreatectomized primates with functioning segmental pancreatic allografts.
• To determine the impact of graft survival and immunosuppression withdrawal on endocrine function.

Main Methods:

• Segmental pancreatic allografts were transplanted into pancreatectomized primates.
• Immunosuppression with TL1 and CSA was administered, followed by termination after 100 days.
• Intravenous glucose tolerance tests (IVGTT), arginine, and tolbutamide stimulation were used to assess glucose, insulin, glucagon, and C-peptide response.

Main Results:

• Normoglycemic primates with mean graft survival of 145 days exhibited moderate glucose intolerance, hypoinsulinemia, and low C-peptide values after immunosuppression withdrawal.
• Severe graft atrophy was observed postmortem in the absence of significant rejection.
• Graft function was significantly impaired compared to normal animals.

Conclusions:

• Segmental pancreatic transplantation in primates leads to significant graft atrophy and impaired islet function, even with effective immunosuppression.
• Whole pancreas transplantation may be a prerequisite for achieving normal or near-normal endocrine function post-transplant.