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 development. Four groups of host rats, including insulin-deficient and insulin-treated streptozotocin-induced diabetic rats, normal controls, and insulin-treated nondiabetic rats, were prepared. After 38 days, rats received ocular implants of E14 fetal rat kidneys. Nine days later the fetal kidney grafts were harvested for analysis of glomerular development and expression of fibronectin, laminin, laminin-beta 2, and alpha-smooth muscle actin and m170, two additional markers of mesangial maturation. The rate of glomerular maturation was delayed in grafts placed in hyperglycemic, insulin-deficient diabetic rats. These glomeruli contained few mesangial cells or matrix, and laminin-beta 2 expression was reduced as compared with controls. Mesangial expression of alpha-smooth muscle actin and m170 was not detected. In contrast, grafts placed in insulin-treated diabetic animals had increased numbers of mesangial cells and expanded mesangial matrix. The content of laminin-beta 2 and expression of m170 and alpha-smooth muscle actin were also increased in these grafts. These data show that hyperglycemia and insulin status influence laminin isoform expression and play important roles in mesangial development.
Abrass
C K
CK
Department of Medicine, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
Spicer
D
D
Berfield
A K
AK
St John
P L
PL
Abrahamson
D R
DR
D000199:Actins / Q000378:metabolism; D000818:Animals; D000867:Anterior Chamber / Q000601:surgery; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D005314:Embryonic and Fetal Development / Q000502:physiology*; D016332:Fetal Tissue Transplantation / Q000502:physiology; D019084:Fluorescent Antibody Technique, Indirect; D005920:Glomerular Mesangium / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D007003:Hypoglycemia / Q000503:physiopathology; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000502:physiology; D007797:Laminin / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D007328:Insulin; D007797:Laminin; C058783:laminin beta2