The role of the growth hormone-insulin-like growth factor axis in glucose homeostasis.
Homeostatic mechanisms normally maintain the plasma glucose concentration within narrow limits despite major fluctuations in supply and demand. There is increasing evidence that the growth hormone (GH)-insulin-like growth factor (IGF) axis may play an important role in glucose metabolism. GH has potent effects on intermediary metabolism, some of which antagonize the actions of insulin. In contrast, IGF-I has insulin-like actions, which are, in the case of glucose metabolism, opposite to those of GH. There is often deranged glucose metabolism in situations where GH is deficient or in excess. The clinical administration of GH or IGF-I results in altered glucose metabolism and changes in insulin resistance. Despite these observations, the precise role of GH and IGF-I and their interactions with insulin in controlling normal glucose homeostasis are unknown. In diabetes, GH secretion is abnormally increased as a result of reduced portal insulin resulting in impaired hepatic IGF-I generation. Evidence suggests that this may contribute to the development of diabetic microvascular complications. IGF-I 'replacement' in diabetes is under investigation and new methods of delivering IGF-I as a complex with IGFBP-3 offer exciting new prospects.
Holt
R I G
RI
Endocrinology Sub-Division, Fetal Origins of Adult Disease Division, University of Southampton, Southampton General Hospital, Southampton, UK. righ@soton.ac.uk
Simpson
H L
HL
Sönksen
P H
PH
D000818:Animals; D030801:Animals, Genetically Modified; D001786:Blood Glucose / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000209:etiology; D013006:Growth Hormone / Q000172:deficiency / Q000378:metabolism* / Q000627:therapeutic use; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000627:therapeutic use
D001786:Blood Glucose; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone