Increased weight gain, nitrogen retention and muscle protein synthesis following treatment of diabetic rats with insulin-like growth factor (IGF)-I and des(1-3)IGF-I.
We have examined the effects of infusing recombinant human growth hormone (hGH), insulin-like growth factor-I (IGF-I), the truncated IGF-I analogue, des(1-3)IGF-I, and insulin over a 7-day period in streptozotocin-induced diabetic rats. IGF-I at a dose of 1.05 or 1.08 mg/kg per day in two experiments increased body weight and nitrogen retention above those of vehicle-infused controls to about 30% of the improvement achieved with 25 or 30 units of insulin/kg per day, but only in the second experiment were the differences statistically significant (P less than 0.05). A 2.5-fold higher IGF-I dose, or des(1-3)IGF-I at 1.08 mg/kg per day, gave effects that were approx. 70% of those obtained with insulin. hGH at 1.38 mg/kg per day was not effective. The IGF peptides, unlike insulin, did not ameliorate the diabetic glucosuria. The improvements in nitrogen balance could be accounted for in part by increases in muscle protein synthesis. Muscle protein breakdown, as assessed by 3-methylhistidine excretion, was inhibited by insulin, but not by the IGF peptides. Carcass fat increased substantially following insulin administration. This did not occur with the IGF peptides, suggesting that IGF predominantly stimulates the growth of lean tissue. IGF-I concentrations and IGF-I-binding proteins in plasma were increased by IGF-I, especially at the higher dose, whereas hGH produced only a transient increase in IGF-I. Des(1-3)IGF-I induced binding proteins, but had only a slight effect on measured IGF-I concentrations. We conclude that IGF peptides stimulate muscle protein synthesis and improve nitrogen balance in diabetes without obviously influencing the abnormal carbohydrate metabolism. Moreover, des(1-3)IGF-I is at least as potent as the full-length IGF-I.
Tomas
F M
FM
CSIRO Division of Human Nutrition, Adelaide, South Australia.
Knowles
S E
SE
Owens
P C
PC
Read
L C
LC
Chandler
C S
CS
Gargosky
S E
SE
Ballard
F J
FJ
D000818:Animals; D002352:Carrier Proteins / Q000097:blood / Q000302:isolation & purification; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects*
D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D009124:Muscle Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C058957:insulin-like growth factor 1, des-(1-3)-; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D009584:Nitrogen