Intraperitoneal insulin is more potent than subcutaneous insulin at restoring hepatic insulin-like growth factor-I mRNA levels in the diabetic rat: a functional role for the portal vascular link.
There is evidence that the hormonal control of hepatic IGF-I production is mediated by GH and insulin. To elucidate the role of these hormones further we administered s.c. or i.p. insulin (at 2.5 and 5.0 IU/day) and/or GH (0.8 IU/day) to rats made diabetic with streptozotocin 16 days previously. Hepatic IGF-I production was then assessed by quantifying hepatic IGF-I mRNA levels by autoradiography of Northern blots. Diabetes resulted in a fivefold reduction in hepatic IGF-I mRNA levels (optical density (OD) of the 0.7-1.1 kb band: controls, 1.3 +/- 0.09; diabetics, 0.28 +/- 0.08; P < 0.01), which was not significantly changed by treatment with s.c. insulin (OD: low dose, 0.55 +/- 0.05; high dose, 0.58 +/- 0.05) or low dose i.p. insulin (OD: 0.40 +/- 0.03). High dose i.p. insulin enhanced hepatic IGF-I mRNA levels (OD: 0.93 +/- 0.23) compared with diabetic rats (P < 0.01) and those given high dose s.c. insulin (P < 0.04), despite the blood glucose values being similar in the treated groups (i.p., 4.72 +/- 0.29 mmol/l; s.c., 3.32 +/- 0.03 mmol/l). Administration of GH alone partially restored the hepatic IGF-I mRNA level (OD: GH-treated, 1.00 +/- 0.05; diabetic, 0.28 +/- 0.08; P < 0.01), whilst having no effect on blood glucose values (diabetic, 36.35 +/- 0.45 mmol/l; GH-treated, 38.65 +/- 2.39 mmol/l). Additional administration of s.c. insulin completely restored IGF-I mRNA levels to those of controls (OD: low dose, 1.35 +/- 0.14; high dose, 1.27 +/- 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)
Russell-Jones
D L
DL
Department of Endocrinology and Chemical Pathology, United Medical and Dental School of Guys Hospital, London, U.K.
Rattray
M
M
Wilson
V J
VJ
Jones
R H
RH
Sönksen
P H
PH
Thomas
C R
CR
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D013006:Growth Hormone / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone