Effects of islet isografts on hemodynamic and vascular filtration changes in diabetic rats.
To assess the reversibility of diabetes-induced increases in regional vascular albumin permeation and blood flow and changes in kidney filtration function, islet isografts were given via the portal vein after 2 mo of streptozocin-induced diabetes in male Lewis rats. One month later, vascular function was assessed in control rats, islet-transplanted diabetic rats, and untreated diabetic rats (6-9 rats/group). Untreated diabetic rats were markedly hyperglycemic, hyperphagic, and polyuric. Transplanted rats were euglycemic within 6 days; 24-h urine volumes were virtually normalized by 2 wk and food consumption was normalized 4 wk after transplantation. Vascular albumin permeation in diabetic rats was significantly increased 1.4- to 1.7-fold in anterior uvea, choroid, retina, sciatic nerve, new granulation tissue, and kidney and was increased 1.1- to 1.3-fold in diaphragm, cecum, and optic nerve. Albumin permeation was not increased in aorta, brain, heart, or forelimb skeletal muscle. Islet transplants significantly reduced but did not completely normalize vascular albumin permeation in most tissues in which it was increased by diabetes but had no effect on albumin permeation in optic nerve, sciatic nerve, and diaphragm. Urinary excretion of endogenous albumin and IgG in diabetic rats was significantly increased 19- and 14-fold, respectively, and was virtually normalized 4 days after islet transplantation. Marked (1.8-fold) increases in glomerular filtration rate (GFR) in diabetic rats were also substantially reduced by islet transplants but remained elevated 1.4-fold control values. Likewise, diabetes-induced increases in regional blood flow were reduced in general but not normalized by islet transplants. These observations indicate that 1) diabetes-induced hemodynamic changes and alterations in vascular filtration function are not rapidly reversed by euglycemia after islet transplantation, 2) diabetes-induced increases in urinary albumin and IgG excretion are more readily normalized by euglycemia than increases in GFR and renal 125I-labeled bovine serum albumin (125I-BSA) filtration, and 3) significant increases in GFR and renal 125I-BSA filtration may not be manifested by albuminuria.
Pugliese
G
G
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Tilton
R G
RG
Chang
K
K
Speedy
A
A
Province
M
M
Eades
D M
DM
Lacy
P E
PE
Kilo
C
C
Williamson
J R
JR
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery; D005919:Glomerular Filtration Rate / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D007294:Inositol / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D008297:Male; D016035:Pancreas Transplantation / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D012039:Regional Blood Flow / Q000502:physiology; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism; D014185:Transplantation, Isogeneic
D007457:Iodine Radioisotopes; D012710:Serum Albumin, Bovine; D007294:Inositol; D013012:Sorbitol