Impaired insulin-like growth factor I-mediated stimulation of glucose incorporation into glycogen in vivo in the ob/ob mouse.
The ability of insulin to modulate glucose metabolism is impaired in insulin resistant ob/ob mice. It has been shown that insulin-like growth factor I stimulates the uptake and metabolism of glucose in muscle through the insulin-like growth factor receptor not the insulin receptor. Thus, we have compared the abilities of insulin-like growth factor I and insulin to stimulate the in vivo incorporation of [14C]-glucose into glycogen in the diaphragm of ob/ob mice and their lean littermates. The animals used in these studies were 12-14 weeks old and the serum insulin levels of the ob/ob mice were 16-fold higher than in their lean littermates. There were no differences in the serum levels of glucose or insulin-like growth factor I. Both insulin and insulin-like growth factor I stimulate the incorporation of [14C]-glucose into glycogen in lean mice. Significant stimulation occurs at doses as low as 1 micrograms/kg of either peptide. The effective doses of insulin and insulin-like growth factor I are quite similar, which indicates that the effect of insulin-like growth factor I is mediated by the insulin-like growth factor receptor and not the insulin receptor. In contrast, greater than 100 micrograms/kg of insulin-like growth factor I is required to stimulate [14C]-glucose incorporation into glycogen in the diaphragm of ob/ob mice. Thus, ob/ob mice are resistant to the action of both insulin and insulin-like growth factor I.(ABSTRACT TRUNCATED AT 250 WORDS)
Cascieri
M A
MA
Department of Biochemical Endocrinology, Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey.
Slater
E E
EE
Vicario
P P
PP
Green
B G
BG
Bayne
M L
ML
Saperstein
R
R
D000818:Animals; D002250:Carbon Radioisotopes; D002462:Cell Membrane / Q000378:metabolism; D003964:Diaphragm / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008820:Mice, Obese / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011972:Receptor, Insulin; D011956:Receptors, Cell Surface / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D006003:Glycogen; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D005947:Glucose