Effects of full-length and truncated insulin-like growth factor-I on nitrogen balance and muscle protein metabolism in nitrogen-restricted rats

1991 ◽  
Vol 128 (1) ◽  
pp. 97-105 ◽  
Author(s):  
F. M. Tomas ◽  
S. E. Knowles ◽  
P. C. Owens ◽  
L. C. Read ◽  
C. S. Chandler ◽  
...  
Keyword(s):  
Body Weight ◽  
Growth Factor ◽  
Muscle Protein ◽  
Analysis Of Covariance ◽  
High Dose ◽  
Insulin Like Growth Factor ◽  
Body Protein ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

ABSTRACT The ability of insulin-like growth factor-I (IGF-I) to protect against losses of body protein during periods of dietary nitrogen restriction has been evaluated in young rats. Recombinant human IGF-I was administered by osmotic pumps at dose rates of 0, 1·2 or 2·9 mg/kg per day over a 7-day period beginning with the transfer of animals from an 18% to a 4% protein diet. A fourth group received the potent truncated IGF-I analogue, des(1–3)IGF-I, at a dose of 1·2 mg/kg per day over a comparable 7-day period. Plasma IGF-I levels were reduced by 60% following nitrogen restriction, a reduction that was partly prevented by IGF-I administration, especially at the higher dose, but not measurably by des(1–3)IGF-I. The major IGF-binding protein circulating in blood, IGFBP-3, demonstrated a similar pattern of change. A significant (P<0·05) protection of body weight was achieved in the low dose IGF-I and des(1–3)IGF-I groups, but only after differences in food intake had been eliminated by analysis of covariance. Nitrogen balances were not significantly different unless analysis of covariance was used to adjust for the nitrogen intakes, whereupon all treatment groups showed improved balance, especially the animals treated with the low IGF-I dose and des(1–3)IGF-I (both P<0·01). The rate of muscle protein breakdown calculated from the urinary excretion of 3-methylhistidine was not significantly altered by the treatments, but fell progressively throughout the 7 days. The fractional rate of muscle protein synthesis measured on the final day was increased by 31, 26 and 21% respectively by the low and high doses of IGF-I and by des(1–3)IGF-I. Organ weights (g/kg body weight) showed no effects of IGF-I treatment except for 16% increases in the weight of kidneys in the high dose IGF-I and the des(1–3)IGF-I groups. Carcass analyses demonstrated higher water and lower fat contents (all P< 0·01) in the same groups. These results suggest that exogenous IGF-I and especially des(1–3)IGF-I can partly protect body protein reserves during nitrogen restriction. Journal of Endocrinology (1991) 128, 97–105

Insulin-like growth factor I preserves host lean tissue mass in cancer cachexia

1992 ◽  
Vol 262 (3) ◽  
pp. R426-R431 ◽  
Author(s):  
E. H. Ng ◽  
C. S. Rock ◽  
D. D. Lazarus ◽  
L. Stiaino-Coico ◽  
L. L. Moldawer ◽  
...  
Keyword(s):  
Growth Factor ◽  
Muscle Protein ◽  
Insulin Like Growth Factor ◽  
Skeletal Muscle Protein ◽  
Lean Tissue ◽  
Tissue Mass ◽  
Fischer 344 ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Insulin-like growth factor I (IGF-I) has been implicated in the regulation and maintenance of skeletal muscle protein balance and thus may be of potential benefit in attenuating the cancer-cachectic process. To examine this hypothesis, 47 sham or tumor-implanted Fischer 344 rats were randomized to receive either continuous subcutaneous IGF-I (220 or 400 micrograms/day) or saline as control. In the tumor-bearing (TB) population, IGF-I-treated groups showed a dose-dependent increase in host weight gain (P less than 0.05), final carcass weight (P less than 0.05), and gastrocnemius muscle weights (P less than 0.05) and protein contents (0.50 +/- 0.02, 0.40 +/- 0.01, and 0.52 +/- 0.03 g/100 g host wt, for non-TB saline, TB saline, and TB 400 mg IGF-I groups, respectively; P less than 0.01, IGF-I vs. saline). Similar increases in muscle RNA and DNA contents (P less than 0.01) were induced by IGF-I treatment (P less than 0.05). IGF-I treatment in this rat sarcoma model significantly reduced the proportion of aneuploid cells in the tumor (aneuploid-to-diploid ratio: TB saline 1.1 +/- 0.2 vs. TB IGF-I 0.5 +/- 0.1; P less than 0.05). IGF-I treatment attenuated host muscle protein and lean tissue depletion without stimulation of tumor growth. The tumor aneuploid population was reduced in response to IGF-I treatment. Thus IGF-I may be a potential therapeutic agent in cancer-induced cachexia.

Insulin-like growth factor I exerts growth hormone- and insulin-like actions on human muscle protein metabolism

1994 ◽  
Vol 267 (2) ◽  
pp. E331-E336 ◽  
Author(s):  
D. A. Fryburg
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Muscle Protein ◽  
Muscle Metabolism ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Muscle Protein Metabolism ◽  
Growth Factor I ◽  
Forearm Muscle

The effect of a 6-h intra-arterial infusion of recombinant human (rh) insulin-like growth factor I (IGF-I) on forearm muscle metabolism was studied in 19 postabsorptive subjects. Forearm glucose, lactate, and phenylalanine (Phe) balances, as well as estimates of protein degradation (Phe Ra) and synthesis (Phe Rd) were measured before and at 3 and 6 h into an infusion of rhIGF-I at a dose of 1.8 (n = 6), 6.0 (n = 8), or 10.0 (n = 5) micrograms.kg-1.h-1. In response to intra-arterial IGF-I, deep venous IGF-I rose by 55, 141, and 315%, respectively (all P < 0.01), and forearm blood flow accelerated by 75 (1.8 microgram), 213 (6.0 micrograms), and 159% (10.0 micrograms; all P < 0.02). No change in forearm glucose uptake was observed at the lowest dose, whereas four- to sixfold increases were observed at both the 6 and 10 micrograms.kg-1.h-1 doses (both P < 0.02). Forearm Phe balance shifted positively at all three doses by 27 +/- 6, 48 +/- 7, and 51 +/- 9 nmol.min-1 x 100 ml-1, respectively (all P < 0.01). At all three doses, Phe Rd increased comparably by 49-74% (all P < 0.05). At the 6.0 and 10.0 but not the 1.8 microgram.kg-1.h-1 dose, Phe Ra decreased by approximately 45% (P < 0.02). Forearm muscle metabolism was also studied in the contralateral non-IGF-infused arm at these three doses. Despite increases in deep venous IGF-I up to 517 ng/ml due to recirculating IGF-I (10.0 micrograms.kg-1.h-1 dose), contralateral forearm muscle glucose, lactate, or Phe handling did not change. In conclusion, intra-arterial IGF-I exhibits growth hormone-like effects at all doses tested, whereas the insulin-like effects are observed at higher doses; these effects appear dependent on the route of administration.

Developmental patterns of plasma insulin-like growth factor-I (IGF-I) and body growth in mice from lines divergently selected on the basis of plasma IGF-I

1990 ◽  
Vol 124 (1) ◽  
pp. 151-158 ◽  
Author(s):  
R. A. Siddiqui ◽  
H. T. Blair ◽  
S. N. McCutcheon ◽  
D. D. S. Mackenzie ◽  
P. D. Gluckman ◽  
...  
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Growth Factor ◽  
Plasma Concentrations ◽  
Body Growth ◽  
Insulin Like Growth Factor ◽  
Developmental Patterns ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

ABSTRACT A study was conducted to investigate developmental patterns of plasma concentrations of insulin-like growth factor-I (IGF-I), body growth and body composition in mice from lines selected for seven generations on the basis of low (L) or high (H) plasma IGF-I, and in a random-bred control (C) line. Litter size was standardized to eight individuals with equal sex ratios (as far as possible) within 48 h of birth. Pups were weaned at an average of 21 days and separated on the basis of sex. Blood samples were collected from one male and one female of each litter on days, 21, 42, 63 and 105 for analysis of plasma concentrations of IGF-I. The animals were then killed and analysed for water, fat and crude protein content. The plasma concentration of IGF-I was influenced by line (P<0·05) but not by sex. Significant (P< 0·001) differences in liveweight between mice from L and H lines were first evident at 21 days of age. From 28 until 105 days of age the H line was significantly (P< 0·001) heavier than both L and C lines, but differences between C and L lines were inconsistent and mostly non-significant. The growth velocity of the H line was significantly greater than that of C or L lines between 14 and 42 days of age, but differences in growth velocities of C compared with L lines were generally non-significant. Nose–anus length was significantly (P<0·01) affected by sex and line from 42 to 105 days of age, but anus–tail length was not affected by sex or line at any age. Effects of sex and line on empty (digesta-free) body weight and wet weights of carcass and skin plus viscera fractions followed a pattern similar to those of liveweights. The effects of sex and line on protein, water and fat content also paralleled their effects on body size. Differences between males and females, and between the lines, in amount of protein, water and fat could be entirely accounted for by the corresponding differences in body weight. It is concluded from these results that divergent selection on the basis of plasma IGF-I at 42 days of age resulted in lines of animals differing in plasma IGF-I from 21 days of age until maturity. These divergent concentrations of IGF-I are associated with differences between the lines in body growth, particularly during the period of accelerated growth at puberty, but not with changes in body composition. Journal of Endocrinology (1990) 124, 151–158

Inhibition of neonatal rat growth and circulating concentrations of insulin-like growth factor-I using an antiserum to rat growth hormone

1989 ◽  
Vol 122 (1) ◽  
pp. 79-86 ◽  
Author(s):  
D. J. Flint ◽  
M. J. Gardner
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Growth Factor ◽  
Body Weight Gain ◽  
Neonatal Rat ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Rat Growth ◽  
Growth Factor I

ABSTRACT Treatment of rats for 24 h on day 2, 10 or 20 of age with a specific antiserum to rGH (anti-(rGH)), GH, bromocriptine (CB-154) or prolactin failed to influence body weight gain or serum concentrations of insulin-like growth factor-I (IGF-I). On day 28 of age, however, anti-(rGH) completely inhibited body weight gain and markedly reduced circulating IGF-I concentrations, effects which were completely prevented by exogenous ovine GH (oGH). When administered to control rats on day 28 oGH caused supranormal weight gain and serum IGF-I concentrations. These results suggested that GH does not play a significant role in growth or regulation of serum IGF-I until after day 20 of age. By contrast, when anti-(rGH) was given for 4 consecutive days beginning on day 2 of life, body weight gain was reduced within 48 h and remained so until at least 28 days of age. Tail length was also significantly reduced. The effect was due to inhibition of GH effects since serum GH concentrations were low and exogenous GH prevented the effect. Inhibition of growth during the first 14 days of life occurred in the absence of any effect on serum IGF-I although by 21 days of age serum IGF-I was considerably lower than in control rats. The prolonged reduction in growth after treatment has stopped appeared to be due to a cytotoxic effect on the pituitary gland since pituitary weight and GH but not prolactin content were significantly decreased. The data are consistent with the hypothesis that in the neonate GH may be processed in serum so that a proportion of it is not recognized by an antiserum to pituitary GH. It would appear that inhibition of GH secretion reduces growth rate by at least 30–40% up to 14 days of age, 50% by 21 days of age and completely by 28 days. Effects of GH on growth could not be fully explained by regulation of serum IGF-I concentrations. Journal of Endocrinology (1989) 122, 79–86

Influence of nutrition and bovine growth hormone (GH) on hepatic GH binding, insulin-like growth factor-I and growth of lambs

1991 ◽  
Vol 128 (2) ◽  
pp. 181-186 ◽  
Author(s):  
J. J. Bass ◽  
J. M. Oldham ◽  
S. C. Hodgkinson ◽  
P. J. Fowke ◽  
H. Sauerwein ◽  
...  
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Growth Factor ◽  
Plasma Glucose ◽  
Specific Binding ◽  
Plasma Concentrations ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

ABSTRACT The effect on young lambs of 0·25 mg recombinant bovine GH (bGH)/kg per day on plasma concentrations of insulin-like growth factor-I (IGF-I), glucose, specific hepatic GH binding and body composition changes was examined at two levels of nutrition (lucerne pellets; 3 and 1·7% of body weight/day). Lambs on low levels of nutrition had low plasma IGF-I (P < 0·001). Plasma concentrations of IGF-I were increased by bGH treatment at both levels of nutrition, with the high nutrition group showing the greatest IGF-I response after 3 and 40 days of bGH treatment. Plasma glucose, after 40 days, was higher overall (P < 0·05) in lambs on high nutrition. bGH treatment increased plasma glucose, with the response being greater in the well-fed lambs. Specific binding of GH to liver membranes was highest in lambs on high nutrition and on bGH treatment; no significant interaction between nutrition and bGH treatment was detected, indicating that specific binding of GH was increased proportionally by bGH at both nutritional levels. The major change in body composition was the reduced level of fatness in lambs treated with bGH. There was no significant effect of bGH on body weight although bGH treatment tended to increase weight gain of well-fed lambs and decreased weight loss of poorly nourished lambs. The results show that, although there was a significant (P < 0·05) bGH/nutrition interaction for IGF-I there was no such interaction for body weight/components or specific GH binding to the liver. The results indicate that an increase in plasma IGF-I does not necessarily result in increases in growth or changes in carcass composition. Journal of Endocrinology (1991) 128, 181–186

Interaction between insulin and insulin-like growth factor I (IGF-I) in rats treated with the high dose of dexamethasone

1998 ◽  
Vol 5 ◽  
pp. 178
Author(s):  
V. Todorovic ◽  
V. Koko ◽  
R. Glisic ◽  
J.A. Nikolic ◽  
M.D. Petakov ◽  
...  
Keyword(s):  
Growth Factor ◽  
High Dose ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Insulin-like growth factor I levels in proportionate dogs, chondrodystrophic dogs and in giant dogs

1988 ◽  
Vol 118 (1) ◽  
pp. 105-108 ◽  
Author(s):  
J. Eugen Eigenmann ◽  
Adel Amador ◽  
Donald F. Patterson
Keyword(s):  
Body Weight ◽  
Body Size ◽  
Growth Factor ◽  
Plasma Insulin ◽  
Plasma Concentrations ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
The Mean ◽  
Growth Factor I

Abstract. Plasma insulin-like growth factor I concentrations from proportionate, chondrodystrophic and giant breeds were evaluated and compared with body size. IGF-I plasma concentrations were 91.2 ± 10.9 μg/l in Keeshounds (proportionate dog), 122.6 ± 25.4 μg/l in Bassethounds (chondrodystrophic dog) and 280 ± 22.8 μg/l in German Shepherds (proportionate dog). The highest IGF-I level (389.6 ± 24.2 μg/l) was found in the New Foundland, a giant breed (mean ± sem). The mean body weight was 11.8 ±0.4 kg in Keeshounds, 15.4 ± 1.4 kg in Bassethounds, 32 ± 1.5 kg in German Shepherds, and 45.6 ± 1.7 kg in New Foundlands (mean ± sem). Body weight and plasma IGF-I concentration were significantly correlated (y (IGF-I) = −7.43 + 8.7 × (body weight); P < 0.0001.

scholarly journals Insulin-like growth factor-I and more potent variants restore growth of diabetic rats without inducing all characteristic insulin effects

1993 ◽  
Vol 291 (3) ◽  
pp. 781-786 ◽  
Author(s):  
F M Tomas ◽  
S E Knowles ◽  
P C Owens ◽  
C S Chandler ◽  
G L Francis ◽  
...  
Keyword(s):  
Growth Factor ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Treated Group ◽  
Diabetic Rats ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

The effects of graded doses of insulin-like growth factor-I (IGF-I) and two variants which bind poorly to IGF-binding proteins were investigated in 160 g streptozotocin-induced diabetic rats. The two variants were the truncated form, des(1-3)IGF-I, and another with arginine at residue 3 and an N-terminal extension, termed LR3-IGF-I. The peptides were infused via mini-osmotic pumps. Reference groups received either vehicle or insulin (30 i.u. per day). Treatment led to a marked dose-dependent increase in growth rate and nitrogen balance. The highest dose (695 micrograms/day) of IGF-I increased body weight by 48.1 +/- 1.7 g/7 days, compared with 11.0 +/- 2.8 g/7 days for the vehicle-treated group. The two variants were 2.5-3 times more potent than IGF-I in restoring growth. The insulin-treated group gained more weight (64.5 +/- 1.6 g/7 days), but the added gain was fat (92.5 +/- 4.8 g of fat/kg carcass wet wt., compared with 32.2 +/- 2.1 for all other groups) rather than protein. All peptides increased muscle protein-synthesis rates and RNA levels by up to 50%, with IGF-I the least potent. These high doses of IGFs did not decrease either the glucosuria or the daily excretion rate of N tau-methyl-histidine (N tau-MH). On the other hand, insulin treatment markedly decreased both glucosuria (from 82.7 +/- 5.4 to 4.5 +/- 3.3 mmol/day) and N tau-MH excretion (from 9.3 +/- 0.3 to 7.1 +/- 0.4 mumol/day per kg). This experiment shows that, although IGF-I and variants can restore growth in diabetic rats, other insulin-dependent metabolic processes in liver, muscle and adipose tissue are not restored.

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