DIABETES INDUCES CHANGES IN GLOMERULAR DEVELOPMENT AND LAMININ-BETA-2(S-LAMININ) EXPRESSION

Offspring of diabetic mothers have developmental renal abnormalities; thus, we investigated the effects of the diabetic milieu on kidney dev elopment. Four groups of host rats, including insulin-deficient and in sulin-treated streptozotocin-induced diabetic rats, normal controls, a nd insulin-treated nondiabetic rats, were prepared. After 38 days, rat s received ocular implants of E14 fetal rat kidneys. Nine days later t he fetal kidney grafts were harvested for analysis of glomerular devel opment and expression of fibronectin, laminin, laminin-beta 2, and alp ha-smooth muscle actin and m170, two additional markers of mesangial m aturation. The rate of glomerular maturation was delayed in grafts pla ced in hyperglycemic, insulin-deficient diabetic rats. These glomeruli contained few mesangial cells or matrix, and laminin-beta 2 expressio n was reduced as compared with controls. Mesangial expression of alpha -smooth muscle actin and m170 was not detected. In contrast, grafts pl aced in insulin-treated diabetic animals had increased numbers of mesa ngial cells and expanded mesangial matrix. The content of laminin-beta 2 and expression of m170 and alpha-smooth muscle actin were also incr eased in these grafts. These data show that hyperglycemia and insulin status influence laminin isoform expression and play important roles i n mesangial development.