Gene expression for endothelins and their receptors in glomeruli of diabetic rats.
The present study was designed to assess levels of messenger RNA encoding for endothelin-1, endothelin-3, and endothelin receptors A and B in glomeruli of rats with streptozotocin-induced diabetes at 4, 12, and 24 weeks of age. In addition, streptozotocin-induced rats with diabetes were either treated with 8 to 14 units neutral protamine Hagedorn insulin daily to maintain moderate hyperglycemia (approximately 200 mg/dl) or left untreated to produce severe hyperglycemia (more than 400 mg/dl) during the 4-week study period. The messenger RNA levels for endothelin-1 in glomeruli of diabetic rats increased with the progression of diabetic nephropathy (4 weeks, 2.5 times control level, p < 0.01; 12 weeks, 3.8 times, p < 0.01; and 24 weeks, 5.3 times, p < 0.001. In contrast, messenger RNA levels for endothelin receptors A and B were not altered in glomeruli from diabetic and control rats throughout the experimental period. Messenger RNA for endothelin-3 in glomeruli from diabetic and control rats was not detected until 24 weeks of age. Insulin treatment partially ameliorated the increase in messenger RNA for endothelin-1 in the glomeruli of diabetic rats (0.3 times compared with diabetic rats without insulin treatment, p < 0.01), whereas insulin treatment did not affect messenger RNA for endothelin receptors A and B in diabetic glomeruli. These findings indicate that increased endothelin-1 messenger RNA in glomeruli may be a manifestation of diabetic nephropathy, and hyperglycemia or insulin-deficiency may play a role in abnormal endothelin-1 gene regulation.
Fukui
M
M
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Nakamura
T
T
Ebihara
I
I
Osada
S
S
Tomino
Y
Y
Masaki
T
T
Goto
K
K
Furuichi
Y
Y
Koide
H
H
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism; D016232:Endothelins / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000096:biosynthesis*
D016232:Endothelins; D007328:Insulin; D012333:RNA, Messenger; D017466:Receptors, Endothelin