The long-term metabolic function of intraportal and renal subcapsular islet isografts and the effect on glomerular basement membrane thickness in rats

Diabetologia
C K LeowP J Morris

Abstract

Previous studies of intraportal islet autotransplantation in large animals have reported graft failure after months or years. In the rat it has been reported that intraportal islet isografts eventually failed whilst islets transplanted to the renal subcapsule functioned up to a year. We made Dark Agouti (DA) rats severely diabetic with streptozotocin, then 1000 or 3000 DA islets were transplanted beneath the renal capsule or into the liver. One set of transplanted rats and untreated diabetic and normal non-diabetic littermates were monitored lifelong by measurement of plasma glucose, others were killed at 6, 12 and 18 months for measurement of haemoglobin A1c, intravenous glucose tolerance test, pancreas insulin content and histology of the kidney. Renal glomerular basement membrane thickness was measured by the orthogonal intercept method. The results showed that intraportal isografts reversed hyperglycaemia significantly faster than renal subcapsular isografts. In the renal subcapsular site, consistent reversal of diabetes was achieved with 3000 islets but not with 1000 islets. Furthermore, intraportal islet grafts with 3000 islets led to lower, normal random glucose level than renal subcapsular grafts for the first 13 months...Continue Reading

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Citations

Jan 15, 1997·Transplantation·C K Leow
Oct 10, 2013·Clinical & Developmental Immunology·Andrew R PepperA M James Shapiro
Nov 11, 2008·The British Journal of Surgery·S MeraniA M J Shapiro
Jul 21, 2010·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Q GaoD P Yin
Jun 13, 2015·Tissue Engineering. Part C, Methods·Masataka HirabaruSusumu Eguchi
Feb 16, 2016·Cell Transplantation·Hajime MatsushimaSusumu Eguchi

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