IGF-I alters skeletal muscle substrate metabolism and blunts recovery from insulin-induced hypoglycemia

1996 ◽  
Vol 270 (4) ◽  
pp. E545-E551 ◽  
Author(s):  
M. A. Hussain ◽  
O. Schmitz ◽  
J. S. Christiansen ◽  
N. J. Christensen ◽  
K. G. Alberti ◽  
...  
Keyword(s):  
Ketone Bodies ◽  
Whole Body ◽  
Elevated Plasma ◽  
Glucose Levels ◽  
Factor I ◽  
Vascular Bed ◽  
Igf I ◽  
The Face ◽  
Delayed Recovery ◽  
Hormone Responses

Eight healthy subjects were treated with saline or insulin-like growth factor I (IGF-I, 10 micrograms.kg-1.h-1 sc) for 3 days in a crossover randomized fashion. Substrate balances across the forearm skeletal vascular bed were determined in the postabsorptive state and during a hyperinsulinemic euglycemic clamp. In the basal state, net forearm uptake of free fatty acids and ketone bodies was increased during IGF-I administration in the face of elevated plasma levels of these substrates, whereas basal glucose levels and forearm glucose balance were unchanged. However, whole body and net forearm glucose uptakes were more markedly stimulated by insulin (+20 and +8%, respectively) in the IGF-I period. Additionally, counterregulatory hormone responses were examined during insulin-induced stepwise hypoglycemia. Responses of growth hormone and glucagon were blunted, those of cortisol and epinephrine were more marked, and that of norepineprine was unchanged during IGF-I administration. These changes were accompanied with delayed recovery from hypoglycemia.

Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A

1994 ◽  
Vol 131 (3) ◽  
pp. 251-257 ◽  
Author(s):  
Peter D Zenobi ◽  
Yvonne Glatz ◽  
Annamarie Keller ◽  
Susanne Graf ◽  
Silvia E Jaeggi-Groisman ◽  
...  
Keyword(s):  
Growth Factor ◽  
Type A ◽  
Metabolic Effects ◽  
Insulin Like Growth Factor ◽  
Severe Insulin Resistance ◽  
Insulin Resistant ◽  
Glucose Levels ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Zenobi PD, Glatz Y, Keller A, Graf S, Jaeggi-Groisman SE, Riesen WF, Schoenle EJ, Froesch ER. Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A. Eur J Endocrinol 1994;131:251–7. ISSN 0804–4643 Severe insulin resistance type A is due to mutations in the insulin receptor gene and is characterized by glucose intolerance or diabetes mellitus, despite extreme hyperinsulinemia, virilization and acanthosis nigricans. At present, there is no therapy for this condition. Recently, we showed that glucose levels in three such patients are promptly lowered by an iv bolus of recombinant human insulin-like growth factor I (rhIGF-I). In the present study, we investigated two of these rare patients again and determined fasting and postprandial glucose, insulin, C-peptide, proinsulin and lipid levels during five control, five treatment and three wash-out days while on a constant diet. Treatment consisted of 2 × 150 μg rhIGF-I/kg sc per day, which elevated total IGF-I levels 4.5-fold above the control. Fasting glucose levels (days 1–5) in the two patients were 9.6±1.3 and 9.2 ± 1.2 mmol/l, respectively, and fell to 4.4±0.4 and 5.1±0.5 mmol/l on treatment days 8–10. Fasting insulin (2950±450 and 690±125 pmol/l), C-peptide (2217±183 and 1317±235 pmol/l) and proinsulin control levels (125±35 and 66±0 pmol/l) also decreased by ~65% during rhIGH-I treatment, as did the respective postprandial levels. Lipid levels hardly changed at all. In conclusion, IGF-I appears to correct partially some metabolic sequelae of severe insulin resistance and may, hence, be used as a new therapeutic agent. E Rudolf Froesch, Department of Internal Medicine, University Hospital, Rämistrasse 100, 8091 Zurich, Switzerland

Passive immunization against circulating insulin-like growth factor-I (IGF-I) increases protein catabolism in lambs: evidence for a physiological role for circulating IGF-I

1992 ◽  
Vol 135 (2) ◽  
pp. 279-284 ◽  
Author(s):  
J. B. Koea ◽  
B. W. Gallaher ◽  
B. H. Breier ◽  
R. G. Douglas ◽  
S. Hodgkinson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Turnover ◽  
Passive Immunization ◽  
Physiological Role ◽  
Whole Body ◽  
Insulin Like Growth Factor ◽  
Protein Catabolism ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

ABSTRACT Primed constant infusions of [14C]urea were used to determine the acute effect of passive immunization against circulating free and protein-bound insulin-like growth factor-I (IGF-I) on the rate of net protein catabolism (NPC) in castrated male lambs fasted for 48 h. Following an intravenous bolus of 50 ml IGF-I antiserum, the rate of NPC increased to a peak 30 min after injection of 1·69 ± 0·16 g/kg per day from a baseline value of 1·45±0·22 g/kg per day (P<0·05, n = 4). In three animals given 50 ml equivalents of the purified immunoglobulin fraction, NPC increased from 1·31 ±0·20 to 1·59±0·16 g/kg per day (P<0·05). A similar trend was observed in animals given 25 ml antiserum (n = 4). The rate of NPC did not increase following a bolus of non-immune serum in control animals and the rate of NPC in the treated lambs returned to control levels within 60 min of antibody injection. Plasma insulin and glucose concentrations in both the treated and control groups were unchanged throughout the study. These data suggest that circulating IGF-I has a physiological role in regulating whole body protein turnover during starvation and possibly other catabolic states. The effect of immunoneutralization of circulating IGF-I is transient and this suggests that while IGF-I has an endocrine role in the regulation of protein turnover, other regulatory mechanisms are involved. Journal of Endocrinology (1992) 135, 279–284

Protein turnover during puberty in normal children

1996 ◽  
Vol 270 (1) ◽  
pp. E79-E84 ◽  
Author(s):  
S. A. Arslanian ◽  
S. C. Kalhan
Keyword(s):  
Insulin Action ◽  
Fat Free Mass ◽  
Whole Body ◽  
Constant Infusion ◽  
Healthy Children ◽  
Normal Children ◽  
Factor I ◽  
Leucine Kinetics ◽  
Igf I ◽  
Percent Suppression

To investigate whether insulin resistance of puberty involves protein metabolism, we compared whole body leucine kinetics in 20 prepubertal Tanner I (TI), and 21 pubertal Tanner II-IV (TII-IV) healthy children. Leucine flux (LRa), oxidation (LOX), and nonoxidative disposal (NOXLD) were measured during primed constant infusion of [1-13C]leucine at baseline and during a stepwise hyperinsulinemic (10 and 40 mU.m-2.min-1)euglycemic clamp in combination with indirect calorimetry. At baseline LRa and LOX were lower in TII-IV vs. TI [LRa: 3.59 +/- 0.17 vs. 4.05 +/- 0.18 mumol.min-1.kg-1 fat-free mass (FFM), P = 0.036; LOX: 0.45 +/- 0.03 vs. 0.59 +/- 0.04 mumol.min-1. FFM-1, P = 0.005], but NOXLD was similar. Insulin-like growth factor I (IGF-I) levels correlated inversely with LRa, NOXLD, and LOX. Energy expenditure correlated positively with LRa, LOX, and NOXLD. During the clamp absolute and percent suppression in LRa were significantly lower in TII-IV than TI. In conclusion, 1) proteolysis and protein oxidation are lower during puberty compared with prepuberty, whereas protein synthesis is unchanged; 2) insulin action in inhibiting proteolysis is decreased during puberty; and 3) increased pubertal IGF-I levels may play a role in decreased protein degradation.

scholarly journals Oral administration of insulin-like growth factor-I from colostral whey reduces blood glucose in streptozotocin-induced diabetic mice

2011 ◽  
Vol 108 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Kyung-A Hwang ◽  
Yu-Jin Hwang ◽  
Woelkyu Ha ◽  
Young-Kug Choo ◽  
Kisung Ko
Keyword(s):  
Blood Glucose ◽  
Growth Factor ◽  
Oral Administration ◽  
Insulin Like Growth Factor ◽  
Diabetic Mice ◽  
Glucose Levels ◽  
Factor I ◽  
Blood Glucose Levels ◽  
Igf I ◽  
Growth Factor I

The aim of the present study was to investigate the effects of oral administration of the insulin-like growth factor-I-rich fraction (IGF-I-RF) from bovine colostral whey on the regulation of blood glucose levels in streptozotocin (STZ)-induced diabetic mice. We obtained a peptide fraction containing IGF-I (10 ng/mg protein) from Holstein colostrum within 24 h after parturition by using ultrafiltration. The blood glucose levels of STZ-induced diabetic mice fed with IGF-I-RF (50 μg/kg per d) were significantly reduced by 11 and 33 % at weeks 2 and 4, respectively (P < 0·05). The body weights of STZ-induced diabetic mice increased following the oral administration of the IGF-I-RF. The kidney weights of STZ-induced diabetic mice decreased significantly (P < 0·05) following the administration of the IGF-I-RF, and the liver weights of STZ-induced diabetic mice decreased significantly (P < 0·05) following the administration of 50 μg/kg per d of the IGF-I-RF. The present results indicate that the IGF-I-RF obtained from Holstein colostrum could be a useful component for an alternative therapeutic modality for the treatment of diabetes in insulin-resistant patients.

Use of a leucine clamp to demonstrate that IGF-I actively stimulates protein synthesis in normal humans

1994 ◽  
Vol 267 (4) ◽  
pp. E591-E598 ◽  
Author(s):  
D. L. Russell-Jones ◽  
A. M. Umpleby ◽  
T. R. Hennessy ◽  
S. B. Bowes ◽  
F. Shojaee-Moradie ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Insulin Infusion ◽  
Whole Body ◽  
Insulin Levels ◽  
Factor I ◽  
Anabolic Action ◽  
Human Volunteers ◽  
Igf I ◽  
Normal Humans ◽  
Normal Human

Insulin-like growth factor I (IGF-I) is thought to mediate the anabolic action of growth hormone. A glucose and amino acid clamp technique was used to investigate the effects of a 3-h intravenous infusion of either 43.7 pmol.kg-1.min-1 (20 micrograms.kg-1.h-1) IGF-I or 3.4 pmol.kg-1.min-1 (0.5 mU.kg-1.min-1) insulin on whole body leucine turnover in five normal human volunteers. During the IGF-I infusion, IGF-I levels increased (P < 0.01; 26.6 +/- 2.8 to 88.9 +/- 14.2 nmol/l) and insulin levels fell (P < 0.05; 0.096 +/- 0.018 to 0.043 +/- 0.009 nmol/l). During the insulin infusion, insulin levels increased (P < 0.01; 0.057 +/- 0.013 to 0.340 +/- 0.099 nmol/l), and there was no change in IGF-I. There was no significant change in leucine production rate (Ra; a measure of protein degradation) during the IGF-I infusion (2.23 +/- 0.17 to 2.13 +/- 0.2 mumol.kg-1.min-1), but there was an increase (P < 0.03) in nonoxidative leucine disposal rate (Rd; a measure of protein synthesis; 1.83 +/- 0.15 to 2.05 +/- 0.21 mumol.kg-1.min-1). In contrast, insulin reduced (P < 0.02) leucine Ra (1.81 +/- 0.24 to 1.47 +/- 0.24 mumol.kg-1.min-1) and had no effect on nonoxidative leucine Rd (1.44 +/- 0.25 to 1.41 +/- 0.22 mumol.kg-1.min-1). We conclude that IGF-I, under conditions of adequate substrate supply, directly increases protein synthesis in contrast to insulin, which exerts its anabolic action by reducing proteolysis.

Effect of methionine-free total parenteral nutrition and insulin-like growth factor I on tumor growth in rats

1997 ◽  
Vol 273 (1) ◽  
pp. E10-E16 ◽  
Author(s):  
S. Yoshida ◽  
J. Ohta ◽  
Y. Shirouzu ◽  
N. Ishibashi ◽  
Y. Harada ◽  
...  
Keyword(s):  
Growth Factor ◽  
Parenteral Nutrition ◽  
Tumor Growth ◽  
Total Parenteral Nutrition ◽  
Whole Body ◽  
Synthesis Rate ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

The objectives of this study were to evaluate the effect of insulin-like growth factor I (IGF-I) on the fractional synthesis rate (FSR) of muscle and whole body protein breakdown rate (WPBR) during methionine-free total parenteral nutrition (MTPN). We also determined whether the inhibition of endogenous methionine availability reduced tumor protein synthesis. AH109A hepatoma cells were inoculated onto the backs of Donryu rats on day 0. On day 10, the rats were catheterized for TPN and assigned to one of four groups: 1) standard TPN (STPN), 2) STPN + IGF-I, 3) MTPN, or 4) MTPN + IGF-I. The addition of IGF-I to MTPN reduced the loss of body weight by both increasing muscle FSR and reducing WPBR. The tumor FSR did not differ between MTPN + IGF-I and MTPN. The methionine extraction ratio from the liver was negative with MTPN + IGF-I but positive in the other groups. We concluded that IGF-I blockage of endogenous methionine release from peripheral protein sites was associated with a shift to liver-derived methionine, with no change in tumor growth in MTPN-treated rats.

scholarly journals Insulin-like Growth Factor I (IGF-I) Increases Whole Body Protein Synthesis in Contrast to Insulin Which Reduces Proteolysis

1994 ◽  
Vol 3 (Supple5) ◽  
pp. 240-240
Author(s):  
David L. Russell-Jones ◽  
Marlot A. Umpleby ◽  
Tom D. Hennessy ◽  
Peter H. Sonksen
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Whole Body ◽  
Insulin Like Growth Factor ◽  
Body Protein ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Greater potency of IGF-I than IGF-I/BP-3 complex in catabolic parenterally fed rats

2000 ◽  
Vol 278 (2) ◽  
pp. E252-E262 ◽  
Author(s):  
K. R. Kritsch ◽  
D. J. Huss ◽  
D. M. Ney
Keyword(s):  
Serum Insulin ◽  
Male Rats ◽  
Total Serum ◽  
Pharmacokinetic Analysis ◽  
Mrna Levels ◽  
Recombinant Human Insulin ◽  
Glucose Levels ◽  
Factor I ◽  
Igf I ◽  
Igfbp 3

We compared the anabolic effects of recombinant human insulin-like growth factor I (rhIGF-I, 2.5 mg/kg) and equimolar amounts of rhIGF-I prebound to rhIGF binding protein-3 (rhIGF-I/BP-3) coinfused continuously with total parenteral nutrition (TPN) solution in dexamethasone (Dex, 70 μg/day ip)-treated male rats for 6 days. The four TPN groups included control, Dex, Dex + IGF-I, and Dex+IGF-I/BP-3. Pharmacokinetic analysis indicated reduced clearance of IGF-I when infused as IGF-I/BP-3 compared with free IGF-I (0.91 ± 0.09 vs. 2.01 ± 0.19 ml serum/min, P < 0.001) and this was associated with significantly greater serum IGF-I concentrations in the Dex+IGF-I/BP-3 group. Despite greater total serum IGF-I levels, infusion of free IGF-I produced greater anabolic responses than IGF-I/BP-3 based on body weight, nitrogen balance, and jejunal cellularity. Treatment with free IGF-I, but not IGF-I/BP-3, significantly reduced serum insulin and glucose levels that were elevated due to Dex. There were no significant differences in liver IGF-I mRNA levels between groups. Serum IGFBP-3 levels were elevated with infusion of IGF-I/BP-3 compared with IGF-I. These results indicate greater anabolic potency of IGF-I compared with IGF-I/BP-3 when administered by continuous parenteral infusion with TPN solution in catabolic rats.

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