ABSTRACT
Pancreatic digestive insufficiency is a common problem in both Type 1 and Type 2 diabetes and remains a serious consequence of diabetes in developing countries. The problem is not corrected by supportive therapies including exogenous insulin injections. It is our hypothesis that digestive insufficiency may be corrected or diminished by the transplantation of islets to the pancreas, thereby supplying islet hormones directly to acinar tissue analogous to the normal pancreas. Diabetic rats received 1000 syngeneic islets and dogs received 7600 autologous islets per kilogram as a transplant to the pancreas. Blood glucose and amylase concentrations were normalized in islet recipients in contrast with controls receiving no islets or islets transplanted to the renal capsule. These results suggest that diabetic digestive insufficiency may be corrected by intrapancreatic islet transplantation.
Subject(s)
Diabetes Complications/complications , Exocrine Pancreatic Insufficiency/etiology , Exocrine Pancreatic Insufficiency/surgery , Islets of Langerhans Transplantation , Amylases/metabolism , Animals , Blood Glucose/metabolism , Diabetes Complications/blood , Diabetes Complications/enzymology , Disease Models, Animal , Dogs , Exocrine Pancreatic Insufficiency/metabolism , Female , Insulin/blood , Male , Rats , Rats, Inbred LewABSTRACT
INTRODUCTION: Transplanted islets, being avascular and denervated, receive blood vessels and nerves from the recipient. Reinnervation may account in part for the normalization of islet function in islet transplants. Whether reinnervation is possible to augment is not known. AIMS AND METHODOLOGY: To explore whether reinnervation of transplanted islets is augmented by local addition of growth factors to the graft, syngeneic islets were transplanted to the pancreas of streptozotocin-diabetic Lewis rats with or without pellets locally releasing nerve growth factor (NGF) and vascular endothelial growth factor (VEGF), alone or in combination. The pellets released growth factors for 14 days at a rate of 20 ng/day. After 7 weeks, pancreatic tissue was processed for immunofluorescence of insulin and the neural markers neuropeptide Y (NPY) and tyrosine hydroxylase (TH). RESULTS: Islets were larger and more numerous after treatment with NGF (p = 0.024) and with NGF in combination with VEGF (p = 0.044). Similarly, immunostaining for TH and the C-terminal flanking peptide of NPY (C-PON) was more pronounced after treatment with NGF in combination with VEGF than in controls (both p < 0.05). CONCLUSION: Local growth factor treatment has a beneficial effect on autonomic reinnervation as well as islet integrity and survival of the graft after islet transplantation in rats.
