Tissue-specific regulation of insulin receptor mRNA levels in rats with STZ-induced diabetes mellitus.
In rats with STZ-induced diabetes mellitus, a reduction in insulin secretion is associated with increased insulin binding in the liver, muscle, fat, and kidney, but not in the brain. To test the hypothesis that tissue-specific modulation of insulin receptors (IRs) in STZ-induced diabetes occurs at the level of mRNA, IR mRNA levels were measured in the liver, kidney, and brain of Sprague-Dawley rats 15 days after intravenous administration of STZ (60 mg/kg body weight) and compared with those of control rats. Diabetic rats were either left untreated or given differing insulin regimens that were designed to achieve varying degrees of metabolic control. IR mRNA levels were measured by slot blot hybridization with a 32P-labeled rIR probe and standardized by 28S ribosomal RNA determination. Hepatic IR mRNA levels were increased significantly in both untreated diabetic rats and in those that received low-dose (2 U/day) insulin therapy. In contrast, hepatic IR mRNA levels did not differ significantly from controls in those that received moderate doses of insulin (3-8 U/day) and were significantly less than controls in those that received the highest doses (6-10 U/day). Renal IR mRNA levels also were increased significantly in the untreated diabetic rats but not in those that received low- or moderate-dose insulin therapy, and were significantly less than controls in those that received the highest doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Sechi
L A
LA
Division of Endocrinology, San Francisco General Hospital, CA 94110.
Griffin
C A
CA
Grady
E F
EF
Grunfeld
C
C
Kalinyak
J E
JE
Schambelan
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D001923:Brain Chemistry; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D007668:Kidney / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D013311:Streptozocin
D007328:Insulin; D012333:RNA, Messenger; D013311:Streptozocin; D011972:Receptor, Insulin