The effect of islet transplantation on complications in experimental diabetes of the rat.

Abstract

AbstractExperimental diabetes in the rat induces secondary complications of kidney, eye, and nervous system similar to the changes observed in humans. Transplantation of a sufficient number of isolated islets from isogeneic donors inhibits or reverses those lesions. Detailed studies have been made in order to examine renal glomerular and tubular lesions in diabetic rats prior to and following transplantation. Streptozotocin‐treated rats after 2 to 3 months begin to develop renal lesions with severe morphological changes, such as enlargement of the mesangial space, thickening of the capillary wall, deposition of IgG and C3, vacuolization of the tubular epithelial cells, and protein casts. Functional disturbances including increased glomular filtration rate, proteinuria, accumulation of basement membrane products (glucosyltransferase in the kidney, laminin P2, 7‐S collagen in serum), and increased excretion of brush border enzymes in the urine also developed. Intraportal islet transplantation leading to normalization of fasting blood glucose and insulin and of body weight either prevented these lesions or reversed early changes. Advanced renal changes are not reversible; however, further progression is halted. The experimental data support the view that rigid control in human diabetics may help to prolong the phase without secondary complications and that islet transplantation in the future may be a useful therapy.