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.

scholarly journals Severe diabetes prohibits elevations in muscle protein synthesis after acute resistance exercise in rats

2000 ◽  
Vol 88 (1) ◽  
pp. 102-108 ◽  
Author(s):  
Mark J. Fedele ◽  
Jazmir M. Hernandez ◽  
Charles H. Lang ◽  
Thomas C. Vary ◽  
Scot R. Kimball ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Critical Concentration ◽  
Diabetic Rats ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I

This study determined whether rates of protein synthesis increase after acute resistance exercise in skeletal muscle from severely diabetic rats. Previous studies consistently show that postexercise rates of protein synthesis are elevated in nondiabetic and moderately diabetic rats. Severely diabetic rats performed acute resistance exercise ( n= 8) or remained sedentary ( n = 8). A group of nondiabetic age-matched rats served as controls ( n = 9). Rates of protein synthesis were measured 16 h after exercise. Plasma glucose concentrations were >500 mg/dl in the diabetic rats. Rates of protein synthesis (nmol phenylalanine incorporated ⋅ g muscle−1 ⋅ h−1, means ± SE) were not different between exercised (117 ± 7) and sedentary (106 ± 9) diabetic rats but were significantly ( P < 0.05) lower than in sedentary nondiabetic rats (162 ± 9) and in exercised nondiabetic rats (197 ± 7). Circulating insulin concentrations were 442 ± 65 pM in nondiabetic rats and 53 ± 11 and 72 ± 19 pM in sedentary and exercised diabetic rats, respectively. Plasma insulin-like growth factor I concentrations were reduced by 33% in diabetic rats compared with nondiabetic rats, and there was no difference between exercised and sedentary diabetic rats. Muscle insulin-like growth factor I was not affected by resistance exercise in diabetic rats. The results show that there is a critical concentration of insulin below which rates of protein synthesis begin to decline in vivo. In contrast to previous studies using less diabetic rats, severely diabetic rats cannot increase rates of protein synthesis after acute resistance exercise.

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.

scholarly journals Fitness, Training, and the Growth Hormone→Insulin-Like Growth Factor I Axis in Prepubertal Girls1

2001 ◽  
Vol 86 (6) ◽  
pp. 2797-2802 ◽  
Author(s):  
Alon Eliakim ◽  
Timothy P. Scheett ◽  
Robert Newcomb ◽  
Subburaman Mohan ◽  
Dan M. Cooper
Keyword(s):  
Growth Factor ◽  
Training Program ◽  
Muscle Volume ◽  
Thigh Muscle ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Prepubertal Girls

We recently demonstrated that a brief endurance type training program led to increases in thigh muscle mass and peak oxygen uptake (V̇O2) in prepubertal girls. In this study, we examined the effect of training on the GH→insulin-like growth factor I (GH→IGF-I) axis, a system known to be involved both in the process of growth and development and in the response to exercise. Healthy girls (mean age 9.17 ± 0.10 yr old) volunteered for the study and were randomized to control (n = 20) and training groups (n = 19) for 5 weeks. Peak V̇O2, thigh muscle volume, and blood samples [for IGF-I, IGF-binding proteins (IGFBP)-1 to -6, and GHBP] were measured. At baseline, IGF-I was significantly correlated with both peak V̇O2 (r = 0.44, P &lt; 0.02) and muscle volume (r = 0.58, P &lt; 0.004). IGFBP-1 was negatively correlated with muscle volume (r = −0.71, P &lt; 0.0001), as was IGFBP-2. IGFBP-4 and -5 were significantly correlated with muscle volume. We found a threshold value of body mass index percentile (by age) of about 71, above which systematic changes in GHBP, IGFBP-1, and peak V̇O2 per kilogram were noted, suggesting decreases in the following: 1) GH function, 2) insulin sensitivity, and 3) fitness. Following the training intervention, IGF-I increased in control (19.4 ± 9.6%, P &lt; 0.05) but not trained subjects, and both IGFBP-3 and GHBP decreased in the training group (−4.2 ± 3.1% and −9.9 ± 3.8%, respectively, P &lt; 0.05). Fitness in prepubertal girls is associated with an activated GH→IGF-I axis, but, paradoxically, early in a training program, children first pass through what appears to be a neuroendocrine state more consistent with catabolism.

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

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