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

Abstract

Summary 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 Alc, 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. Normoglycaemia was maintained lifelong in all rats that achieved early normoglycaemia after transplantation of 3000 islets, irrespective of the site of islet transplantation. The fasting glucose, haemoglobin Alc levels, K value and glomerular basement membrane thickness of the recipients of 3000 islets to either the intraportal and subcapsular site were not significantly different from each other and the normal controls up to 18 months. We conclude that, in streptozotocin diabetic DA rats, normoglycaemia following transplantation of an adequate mass of pancreatic islet tissue (3000 islets) to the liver or beneath the renal capsule is lifelong and the development of glomerular basement membrane thickening is prevented. [Diabetologia (1995[Diabetologia ( ) 38: 1014[Diabetologia ( -1024