Effects of insulin--like growth factor-I treatment on the endocrine pancreas of hypophysectomized rats: comparison with growth hormone replacement.
BACKGROUND
In GH-deficient humans, GH and IGF-I treatment cause opposite effects on serum insulin concentrations and insulin sensitivity. This finding contrasts with the somatomedin hypothesis that IGF-I mediates GH action, as postulated for skeletal growth, and raises the question whether GH-induced IGF-I acts on the endocrine pancreas in the same way as administered IGF-I.


OBJECTIVE
To compare the effects of the two hormones on the endocrine pancreas of hypophysectomized rats.


METHODS
Animals were infused for 2 days, via miniosmotic pumps, with IGF-I (300 microg/day), GH (200 mU/day) or vehicle. We measured (i) glucose, IGF-I, insulin, C-peptide and glucagon in serum and (ii) IGF-I, insulin and glucagon mRNAs and peptides in the pancreas by radioimmunoassay, immunohistochemistry and northern analysis.


RESULTS
Both GH and IGF-I treatment increased serum and pancreatic IGF-I but, unlike GH, IGF-I treatment strongly reduced serum insulin and C-peptide (and, to a lesser extent, serum glucagon). Nevertheless, the animals did not become hyperglycaemic. GH, but not IGF-I, increased pancreatic insulin and glucagon content, as also indicated by immunohistochemistry, and increased IGF-I mRNA. Neither GH nor IGF-I caused significant changes in insulin and glucagon mRNA.


CONCLUSIONS
The decrease in serum insulin and C-peptide by IGF-I treatment without significant changes in insulin gene expression and pancreatic insulin content suggests inhibition of insulin secretion. Within this setting, the absence of hyperglycaemia points to enhanced insulin sensitivity, although an insulin-like action of infused IGF-I may have partially compensated for the decreased insulin concentrations. GH-induced circulating or pancreatic IGF-I, or both, does not mimic the pancreatic effects of infused IGF-I in the absence of GH, suggesting that GH may counteract the action of GH-induced IGF-I on the endocrine pancreas.
Division of Neuroendocrinology, Institute of Anatomy, University of Zurich, Winterthurerstr. 190, CH-8057 Zurich, Switzerland.
T
T
Jevdjovic
C
C
Maake
E
E
Eppler
E
E
Zoidis
M
M
Reinecke
J
J
Zapf
D000818:Animals; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D005455:Fluorescent Antibody Technique; D005934:Glucagon / Q000097:blood / Q000235:genetics; D013006:Growth Hormone / Q000097:blood / Q000494:pharmacology*; D007016:Hypophysectomy; D007328:Insulin / Q000097:blood / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010900:Pituitary Diseases / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005934:Glucagon