Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice.
Growth hormone, acting through its receptor (GHR), plays an important role in carbohydrate metabolism and in promoting postnatal growth. GHR gene-deficient (GHR(-/-)) mice exhibit severe growth retardation and proportionate dwarfism. To assess the physiological relevance of growth hormone actions, GHR(-/-) mice were used to investigate their phenotype in glucose metabolism and pancreatic islet function. Adult GHR(-/-) mice exhibited significant reductions in the levels of blood glucose and insulin, as well as insulin mRNA accumulation. Immunohistochemical analysis of pancreatic sections revealed normal distribution of the islets despite a significantly smaller size. The average size of the islets found in GHR(-/-) mice was only one-third of that in wild-type littermates. Total beta-cell mass was reduced 4.5-fold in GHR(-/-) mice, significantly more than their body size reduction. This reduction in pancreatic islet mass appears to be related to decreases in proliferation and cell growth. GHR(-/-) mice were different from the human Laron syndrome in serum insulin level, insulin responsiveness, and obesity. We conclude that growth hormone signaling is essential for maintaining pancreatic islet size, stimulating islet hormone production, and maintaining normal insulin sensitivity and glucose homeostasis.
Liu
Jun-Li
JL
Fraser Laboratories, Department of Medicine, McGill University, Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada. jun-li.liu@mcgill.ca
Coschigano
Karen T
KT
Robertson
Katie
K
Lipsett
Mark
M
Guo
Yubin
Y
Kopchick
John J
JJ
Kumar
Ujendra
U
Liu
Ye Lauren
YL
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002455:Cell Division; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000502:physiology*; D006706:Homeostasis; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007515:Islets of Langerhans / Q000033:anatomy & histology* / Q000254:growth & development; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009765:Obesity / Q000235:genetics; D011986:Receptors, Somatotropin / Q000235:genetics / Q000502:physiology*
D001786:Blood Glucose; D007328:Insulin; D011986:Receptors, Somatotropin; D013006:Growth Hormone; D005934:Glucagon; D005947:Glucose