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J M Ketelslegers

Publications and source records attributed to J M Ketelslegers.

At least 19 recordsLinked to original sources
PubMed2006

Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy.

Glucocorticoids mediate muscle atrophy in many catabolic states. Myostatin expression, a negative regulator of muscle growth, is increased by glucocorticoids and myostatin overexpression is associated with lower muscle mass. This suggests that myostatin is required for the catabolic effects of glucocorticoids. We therefore investigated whether myostatin gene disruption could prevent muscle atrophy caused by glucocorticoids. Male myostatin knockout (KO) and wild-type mice were subjected to dexamethasone treatment (1 mg/kg.d for 10 d or 5 mg/kg.d for 4 d). In wild-type mice, daily administration of low-dose dexamethasone for 10 d resulted in muscle atrophy (tibialis anterior: -15%; gastrocnemius: -13%; P < 0.01) due to 15% decrease in the muscle fiber cross-sectional area (1621 +/- 31 vs. 1918 +/- 64 microm(2), P < 0.01). In KO mice, there was no reduction of muscle mass nor fiber cross-sectional area after dexamethasone treatment. Muscle atrophy after 4 d of high-dose dexamethasone was associated with increased mRNA of enzymes involved in proteolytic pathways (atrogin-1, muscle ring finger 1, and cathepsin L) and increased chymotrypsin-like proteasomal activity. In contrast, the mRNA of these enzymes and the proteasomal activity were not significantly affected by dexamethasone in KO mice. Muscle IGF-I mRNA was paradoxically decreased in KO mice (-35%, P < 0.05); this was associated with a potentially compensatory increase of IGF-II expression in both saline and dexamethasone-treated KO mice (2-fold, P < 0.01). In conclusion, our results show that myostatin deletion prevents muscle atrophy in glucocorticoid-treated mice, by blunting the glucocorticoid-induced enhanced proteolysis, and suggest an important role of myostatin in muscle atrophy caused by glucocorticoids.

Animals↗
PubMed2005

Circulating urotensin II levels in moderate to severe congestive heart failure: its relations with myocardial function and well established neurohormonal markers.

Urotensin II (UII) is a potent vasoactive cyclic peptide thought to play a role in myocardial hypertrophy and remodelling. We therefore determined UII plasma levels in congestive heart failure (CHF) patients and its relationship with the severity of the disease and well-established markers of left ventricular function. UII was significantly higher in CHF patients (n = 57) than in controls (n = 48) [geometric mean (pg/ml), 95% PI: 1.32 (0.67-2.59) versus 0.84 (0.31-1.61), p < 0.0001], was related to the functional class of the disease and correlated negatively with left ventricular ejection fraction (r = -0.316, P = 0.016). Furthermore, UII correlated significantly with Big-ET1 (r = 0.32, p = 0.03), BNP (r = 0.42, p = 0.005) but poorly with Nt-proANP (r = 0.28, p = 0.07). Our results suggest that UII could play a role in worsening the course of congestive heart failure and is associated with established markers of cardiovascular dysfunction.

Aged↗
PubMed2005

Insulin-like growth factor-I gene transfer by electroporation prevents skeletal muscle atrophy in glucocorticoid-treated rats.

Catabolic states caused by injury are characterized by a loss of skeletal muscle. The anabolic action of IGF-I on muscle and the reduction of its muscle content in response to injury suggest that restoration of muscle IGF-I content might prevent skeletal muscle loss caused by injury. We investigated whether local overexpression of IGF-I protein by gene transfer could prevent skeletal muscle atrophy induced by glucocorticoids, a crucial mediator of muscle atrophy in catabolic states. Localized overexpression of IGF-I in tibialis anterior (TA) muscle was performed by injection of IGF-I cDNA followed by electroporation 3 d before starting dexamethasone injections (0.1 mg/kg.d sc). A control plasmid was electroporated in the contralateral TA muscle. Dexamethasone induced atrophy of the TA muscle as illustrated by reduction in muscle mass (403 +/- 11 vs. 461 +/- 19 mg, P < 0.05) and fiber cross-sectional area (1759 +/- 131 vs. 2517 +/- 93 mum(2), P < 0.05). This muscle atrophy was paralleled by a decrease in the IGF-I muscle content (7.2 +/- 0.9 vs. 15.7 +/- 1.4 ng/g of muscle, P < 0.001). As the result of IGF-I gene transfer, the IGF-I muscle content increased 2-fold (15.8 +/- 1.2 vs. 7.2 +/- 0.9 ng/g of muscle, P < 0.001). In addition, the muscle mass (437 +/- 8 vs. 403 +/- 11 mg, P < 0.01) and the fiber cross-sectional area (2269 +/- 129 vs. 1759 +/- 131 mum(2), P < 0.05) were increased in the TA muscle electroporated with IGF-I DNA, compared with the contralateral muscle electroporated with a control plasmid. Our results show therefore that IGF-I gene transfer by electroporation prevents muscle atrophy in glucocorticoid-treated rats. Our observation supports the important role of decreased muscle IGF-I in the muscle atrophy caused by glucocorticoids.

Animals↗
PubMed2003

Expression of the serotonin 1b receptor in experimental pulmonary hypertension.

The pathogenesis of pulmonary arterial hypertension (PAH) remains uncertain. Both the serotonin and endothelin (ET) systems are believed to be involved. Recent studies pointed to the importance of the serotonin 2B receptor as a limiting step. The current authors investigated the lung tissue expression of serotonin receptors and of the serotonin transporter (5-HTT) by real-time-quantitative polymerase chain reaction in chronic overcirculation-induced PAH in growing piglets, with and without treatment with the dual ET receptor blocker bosentan. Pulmonary haemodynamic changes were described by pulmonary arterial impedance spectra. Three months after the surgical anastomosis of the left subclavian artery to the pulmonary arterial trunk, there was a shift of the impedance spectra to higher ratios of pressure and flow moduli, with increases in both 0 Hz impedance and characteristic impedance, and these changes were completely prevented by bosentan therapy. There was an increase in the expression of the serotonin 1B receptor. There was no change in the expression of the 5-HTT, and of the serotonin 2B, 1D, and 4 receptors. The overexpression of the serotonin 1B receptor was partially prevented by bosentan therapy. The present authors conclude that this early pulmonary arterial hypertension model is characterised by an endothelin receptor-dependent increased expression of the serotonin 1B receptor.

Animals↗
PubMed2000

Direct comparison between endothelin-1, N-terminal proatrial natriuretic factor, and brain natriuretic peptide as prognostic markers of survival in congestive heart failure.

BACKGROUND: Endothelin-1 (ET-1) and cardiac natriuretic peptide plasma concentrations have prognostic significance in congestive heart failure (CHF). However, their respective prognostic values in this setting have never been directly compared. METHODS AND RESULTS: We studied the prognostic performances of ET-1, N-terminal proatrial natriuretic factor (N-proANF), and brain natriuretic peptide (BNP) to predict the long-term cardiac mortality in fully treated patients with CHF. Peripheral plasma concentrations of the 3 peptides were measured in 109 patients (left ventricular ejection fraction [LVEF] < 35%) in New York Heart Association (NYHA) functional classes II (n = 65) or III to IV (n = 44). The outcome of the patients was evaluated 3 years after the beginning of the study, and a Cox regression model was used to identify predictors of death. Plasma concentrations of the 3 peptides increased with the severity of heart failure. By univariate analysis, 6 parameters were significantly associated with death during follow-up: ET-1 level, NYHA classes III to IV, N-proANF level, BNP level, LVEF, and age (all P < .01). By multivariate analysis, only ET-1 level and, to a lesser extent, N-proANF level contributed significantly and independently to risk stratification (chi2 = 53.4 and 12.8; P < .0001 and P < .001, respectively). CONCLUSION: In a group of patients in whom the vast majority were administered angiotensin-converting enzyme inhibitor therapy, plasma ET-1 and N-proANF concentrations identify better than several clinical markers a very high-risk group, fairly amenable to heart transplantation or new therapies.

Aged↗
PubMed1999

Inhibition of insulin-like growth factor-I mitogenic action by zinc chelation is associated with a decreased mitogen-activated protein kinase activation in RAT-1 fibroblasts.

The mechanisms responsible for the resistance to the anabolic actions of IGF-I induced by zinc deficiency are not understood. We showed that zinc chelation by DTPA (diethylenetriaminepenta-acetic acid) inhibits [3H]thymidine incorporation stimulated by IGF-I in Rat-1 fibroblasts. This inhibition was specific of zinc chelation since it was prevented by the addition of zinc to DTPA. The stimulation of MAPK, which is crucial for the [3H]thymidine incorporation induced by IGF-I in Rat-1 cells, was partially blunted by DTPA. Therefore, the inhibition of the mitogenic action of IGF-I in Rat-1 fibroblasts by DTPA is potentially caused by decreased MAPK activation by IGF-I.

Animals↗
PubMed1999

Dexamethasone inhibits both growth hormone (GH)-induction of insulin-like growth factor-I (IGF-I) mRNA and GH receptor (GHR) mRNA levels in rat primary cultured hepatocytes.

Glucocorticoids are potent inhibitors of growth. In this work, we investigated whether glucocorticoids inhibit the stimulatory action of GH on IGF-I gene expression in rat hepatocytes. GH increased IGF-I mRNA levels 11-fold after 24 h, whereas high doses of DXM (10(-6)M) caused a slight (2.6-fold) increase of IGF-I mRNA levels. However, high doses of DXM (10(-6)M) inhibited the induction of IGF-I mRNA by GH. To assess the role of GHR in this inhibition, we investigated the regulation of GHR expression. High doses of DXM decreased GHR mRNA levels. This effect was already detectable 6 h after addition of 10(-6)M DXM and was dose-dependent, with a maximal inhibition observed at a concentration of 10(-6)M. In conclusion, our results show that high doses of DXM inhibits the GH-induced IGF-I gene expression and the GHR gene expression. The parallel decrease of GHR and GH-induced IGF-I mRNA suggests that the GH resistance caused by DXM is mediated by diminished GH receptor synthesis.

Animals↗
PubMed1999

Regulation of insulin-like growth factor-I in starvation and injury.

Both starvation and sepsis are characterized by growth hormone (GH) insensitivity, which leads to a reduction in circulating insulin-like growth factor (IGF)-I. Because of the anabolic properties of this growth factor, its decline may contribute to the growth arrest and the catabolic reaction observed in starvation and sepsis. This review focuses on the mechanisms responsible for the reduction in circulating IGF-I and impairment of GH responsiveness that occur during starvation and sepsis. A clearer understanding of the complex nature of GH resistance should lead to the development of new therapeutic strategies aimed at restoring the beneficial effects of anabolic agents such as GH and IGF-I.

Energy Intake↗
PubMed1999

GH insensitivity induced by endotoxin injection is associated with decreased liver GH receptors.

Sepsis induces a state of growth hormone (GH) resistance associated with a decrease of circulating insulin-like growth factor (IGF) I, a GH-dependent anabolic hormone mainly produced by the liver. To address the mechanisms that might trigger GH insensitivity in sepsis, we investigated the regulation of liver GH receptor (GHR) and its gene expression by endotoxin. Endotoxin injection in rats decreased serum IGF-I and liver GH-binding sites after 10 h. In contrast to liver GHR, circulating GH-binding protein (GHBP) levels were not significantly reduced after endotoxin injection. The parallel decrease in IGF-I and GHR and in their corresponding liver mRNAs suggests that decreased serum IGF-I and liver GHR were likely to result from decreased liver synthesis. Although GH administration in control animals significantly enhanced serum IGF-I, it did fail to prevent the decline in serum IGF-I and liver GH-binding sites in endotoxemic rats. In this study, we showed that endotoxin injection induces a state of GH insensitivity associated with decreased liver GHR. This decline in GHR, which cannot be prevented by exogenous GH, might contribute to the GH insensitivity observed in sepsis.

Animals↗
PubMed1999

Monoclonal antibodies to growth hormone (GH) prolong liver GH binding and GH-induced IGF-I/IGFBP-3 synthesis.

This time-course study further explored the mechanisms whereby monoclonal antibodies (MAbs) may enhance growth hormone (GH) effects. Hypophysectomized rats were killed 0, 1, 3, 6, 12, 24, and 48 h after a single injection of bovine (b) GH alone or complexed with an anti-bGH MAb. Serum insulin-like growth factor I (IGF-I) concentrations were increased more and for a longer period after MAb-GH complexes (peak at 24 h: 295 +/- 24 ng/ml) than after bGH alone (peak at 12 h: 219 +/- 37 ng/ml; P < 0.01), whereas liver IGF-I mRNA was similar at 12 h in both groups but remained higher at 24 h (by 65%, P < 0.001) and 48 h (by 64%, P < 0.001) in the presence of the MAb. Induction of serum insulin-like growth factor-binding protein (IGFBP)-3 and liver IGFBP-3 mRNA by bGH also was markedly amplified by the MAb (3.6- and 2-fold at 24 h, respectively; P < 0.01). GH receptors (GHR) remained occupied for a longer period after MAb-GH injection (36 +/- 16 and 35 +/- 8% at 6 and 12 h, respectively) compared with bGH alone (0 +/- 28 and -15 +/- 11%), whereas total liver GH-binding sites and GHR mRNA levels were not affected by the MAb. We conclude that MAbs against GH amplify and prolong the serum IGF-I response to GH, which may result from both a prolongation of liver IGF-I synthesis and an enhanced induction of IGFBP-3. These two effects may in turn be the consequences of sustained GH binding to its liver receptors in the presence of MAb.

Animals↗
PubMed1998

Zinc regulation of insulin-like growth factor-I (IGF-I), growth hormone receptor (GHR) and binding protein (GHBP) gene expression in rat cultured hepatocytes.

Dietary zinc depletion in vivo attenuates growth, decreases circulating insulin-like growth factor-I (IGF-I) and liver growth hormone (GH) receptors (GHR). In order to investigate a direct role of zinc in the regulation of IGF-I, GHR and GH binding protein (GHBP) gene expression, we evaluated the response of their mRNAs to changes in zinc availability in primary culture of rat hepatocytes. Exposition of cells to the zinc chelator DTPA (diethylenetriaminepenta-acetic acid) did not decrease IGF-I and GHBP mRNAs while it strongly inhibited metallothionein (MT) gene expression. On the other hand, zinc excess (50 vs. 1.5 microM) decreased IGF-I, GHR and GHBP mRNAs while it stimulated MT mRNA. However, the response of IGF-I to GH was not affected by the exposure to DTPA nor zinc excess. Furthermore, zinc repletion of primary cultured hepatocytes isolated from zinc-deprived rats did not increase IGF-I nor GHR/GHBP mRNAs. Therefore, our results suggest that the IGF-I decline induced in vivo by zinc deficiency is not caused by reduced extracellular zinc availability at the hepatocyte level. Although IGF-I and MT gene expression is down-regulated by dietary zinc depletion, underlying mechanisms of regulation are different for both genes.

Animals↗
PubMed1998

Changes in blood pressure and in vasoactive and volume regulatory hormones during semistarvation in obese subjects.

The mechanisms underlying the reduction in blood pressure that occurs with a severe energy-restricted diet were evaluated in 12 obese subjects during 8 days on a very-low-calorie diet (1.67 MJ/d) with a constant intake of 17 mmol sodium per day. The relationship between changes in blood pressure, sodium balance, plasma volume, renin-aldosterone and sympathetic nervous system activities, plasma C-terminus and N-terminus of the atrial natriuretic factor (ANF) prohormone, brain natriuretic peptide (BNP), and endothelin-1 (ET-1) concentrations was investigated. A negative sodium balance was present throughout the diet and was associated with a moderate reduction in plasma volume, a marked activation of the renin-aldosterone system, and a concomitant reduction in C- and N-terminal ANF prohormone levels. Moreover, the postural changes in N-terminal proANF and ANF secretion documented before the diet, disappeared after 8 days of dieting, in contrast to a greater postural stimulation of aldosterone and renin. A negative correlation was found between the changes of C- and N-terminal ANF prohormone levels and those of aldosterone. Urinary catecholamine excretion, BNP, and ET-1 remained unchanged. These results indicate that the decrease in blood pressure occurring during severe caloric restriction was essentially due to the reduction in the effective blood volume, as reflected by the stimulation of the renin-aldosterone system and the decrease in ANF levels. The lack of any changes in catecholamine excretion and endothelin levels suggests that peripheral vascular resistance did not change significantly in these circumstances.

Adolescent↗
PubMed1998

Decreased acid-labile subunit (ALS) levels by endotoxin in vivo and by interleukin-1beta in vitro.

The production by the liver of the three subunits of the growth hormone (GH)-dependent 150 kDa complex (IGF-I, IGF-binding protein-3 and acid-labile subunit or ALS) is primarily under the control of GH. Recent data have shown that, besides GH, endotoxin (LPS) and cytokines may regulate the liver IGF-I gene. To investigate the potential regulation of ALS by LPS, we measured serum ALS by immunoblot, 5 and 10 h after IP injection of LPS (250 or 750 microg/100 g BW vs saline), in 4-week-old female Wistar rats (four per group). Ten hours after injection, serum ALS levels were reduced by 57% (delta%) with the lower dose (P<0.05) and by 81% with the higher dose (P<0.01) by comparison with saline-treated rats. The decrease in ALS levels in response to LPS was not prevented by exogenous GH. To investigate the role of interleukin (IL)-1beta in the regulation of ALS, primary cultured rat hepatocytes were exposed to increasing concentrations of IL-1beta. Cell exposure to IL-1beta markedly decreased both basal and GH-stimulated ALS levels (-70%; P<0.01) in a dose-dependent fashion, with the half-maximal inhibitory effect at concentrations of 0.1 ng/ml. Our results show that endotoxin induces a rapid decline in circulating ALS that is potentially mediated through IL-1beta. By limiting the formation of the 150 kDa complex, this reduction in circulating ALS might contribute to the rapid decline in serum IGF-I observed in sepsis.

Animals↗
PubMed1998

Continuous administration of growth hormone does not prevent the decrease of IGF-I gene expression in zinc-deprived rats despite normalization of liver GH binding.

To determine the role of reduced liver GH binding (GHR) in the decreased IGF-I observed in zinc-deficient (ZD) animals, we investigated the effects of GHR restoration on growth, insulin-like growth factor I (IGF-I) and its binding proteins (IGFBPs) in ZD rats. Rats were fed for 4 weeks a zinc-deficient diet (ZD Zn, 0 ppm) or a Zinc-normal diet (pair-fed or PF; Zn, 75 ppm). ZD rats received continuous s.c. infusion of bovine growth hormone (bGH) (100 microg/d) for the 4 weeks or for the last week of the study. Compared with pair-fed rats, zinc deficiency produced attenuated weight gain (-43%, P < 0.001), lower serum IGF-I and liver IGF-I mRNA (-52%, P < 0.001 and -44%, P < 0.05), lower serum IGFBPs (IGFBP-3 -66%, IGFBP-4 -48%, 34-29 kDa IGFBP cluster -53%, P < 0.05), lower liver GHR and its mRNA (-20 and -34%, P < 0.05) and lower serum growth hormone binding protein (GHBP) and its mRNA (-56 and -48%, P < 0.05; all comparisons vs PF rats). Exogenous bGH given continuously normalized the liver GHR, serum GHBP and their liver mRNAs, as well as circulating IGFBPs. Despite restoration of GHR and GHBP to normal, growth, serum IGF-I and its liver mRNA were not stimulated by GH infusion in ZD rats, indicating that IGF-I synthesis requires the presence of zinc in addition to GH, and that the lack of growth-promoting action of GH in zinc-deprived rats results from a defect beyond GH binding to its liver receptors.

Animals↗
PubMed1998

Cardiac natriuretic peptides for diagnosis and risk stratification in heart failure: influences of left ventricular dysfunction and coronary artery disease on cardiac hormonal activation.

BACKGROUND: Cardiac natriuretic peptides are activated in heart failure. However, their diagnostic and prognostic values have not been compared under the routine conditions of an outpatient practice. METHODS: We studied the diagnostic and prognostic value of plasma N- and C-terminal peptides of the atrial natriuretic factor prohormone (N-proANF and ANF respectively) and brain natriuretic peptide (BNP) to evaluate the severity of congestive heart failure (CHF) as reflected by the New York Heart Association (NYHA) classification and to predict its 2-year mortality. Peripheral plasma concentrations of the three natriuretic peptides were measured in 27 normal subjects (CTR), in 32 patients with coronary artery disease (CAD) and normal left ventricular ejection fraction and in 101 patients with chronic CHF in functional classes I and II (n = 61) or III and IV (n = 40). RESULTS: Plasma concentrations of the three peptides increased in the presence of CHF in relation to its severity (P < 0.01). BNP was unable to distinguish CTR from CAD, just as ANF could not differentiate CAD from CHF I-II; only N-proANF displayed a significant and continuous increase from CTR to CAD, CHF I-II and III-IV. Receiver-operating characteristic curves showed better evaluation of the degree of CHF by BNP than by ANF or ejection fraction (P < 0.05). Assessment of the 2-year prognosis revealed that N-proANF and BNP were the best independent predictors of outcome after the NYHA classification. These peptides identify a very high-mortality group. CONCLUSION: Plasma N-proANF and BNP concentrations are good indicators of the severity and prognosis of CHF in an outpatient practice. CAD does not stimulate BNP as long as ventricular dysfunction is not present, although increased N-proANF levels in this setting suggest an early humoral activation.

Aged↗
PubMed1998

Angiotensin II and endothelin-1 receptor antagonists have cumulative hypotensive effects in canine Page hypertension.

OBJECTIVE: To evaluate whether the cumulative hypotensive effect of the endothelin-1 receptor antagonist bosentan, previously demonstrated in the presence of an angiotensin converting enzyme inhibitor, persists under angiotensin II receptor blockade with losartan. DESIGN: The model of hypertension was canine renovascular hypertension (Page hypertension). METHODS: Ten conscious dogs, studied on two occasions, were administered losartan (a 0.1 mg/kg bolus plus 90 min infusion at 0.1 mg/kg per min) and then bosentan vehicle (experiment I) or losartan and then two cumulative doses of bosentan (a 0.3 mg/kg bolus plus 30 min infusion at 0.7 mg/kg per min; and a 3 mg/kg bolus plus 30 min infusion at 7 mg/kg per min; experiment II). RESULTS: At the end of the study, mean aortic pressure in dogs had decreased by 14% in experiment I (from 139 +/- 4.7 to 119 +/- 4.7 mmHg, P<0.05), whereas a 28% reduction occurred in experiment II (from 145 +/- 8.9 to 104 +/- 5.0 mmHg, P<0.005), corresponding to an additional 14% decrease after administration of bosentan (P<0.005 between groups). This cumulative effect of bosentan was related to a decrease in systemic vascular resistance (from 1220 +/- 119 to 847 +/- 189 mmHg/ml per min per kg x 10(3), P<0.05). Plasma angiotensin II level increased similarly in both experiments (in experiment I from 133 +/- 43 to 622 +/- 145 pg/ml, P=0.01; in experiment II from 198 +/- 63 to 771 +/- 134 pg/ml, P<0.005) whereas plasma endothelin-1 level increased only in experiment II (from 3.8 +/- 0.4 to 32.7 +/- 3.2 pg/ml, P<0.001). CONCLUSION: The cumulative hypotensive effect of bosentan suggests that, besides angiotensin II, endothelin-1 is independently involved in the pathophysiology of hypertension, which presents new therapeutic perspectives.

Angiotensin II↗
PubMed1998

Failure of exogenous IGF-I to restore normal growth in rats submitted to dietary zinc deprivation.

Dietary zinc deficiency in rats causes growth retardation associated with decreased circulating IGF-I concentrations. To investigate the potential role of low IGF-I in this condition, we attempted to reverse the growth failure by administration of exogenous IGF-I. Rats were fed for 4 weeks a zinc-deficient diet (ZD, Zn 0 ppm) or were pair-fed a zinc-normal diet (PF, Zn 75 ppm). We compared the anabolic action of recombinant human (rh) IGF-I infused at the dose of 120 microg/day for the last experimental week in ZD, PF and freely fed control (CTRL) rats. Zinc deficiency caused growth stunting (weight gain 47% of PF; P<0.001), decreased circulating IGF-I (52% of PF; P<0.01) and liver IGF-I mRNA (67% of PF; P<0.01). Serum insulin-like growth factor-binding protein-3 (IGFBP-3) assessed by ligand blot was also reduced in ZD rats (65% of PF; P<0. 01). While exogenous IGF-I increased body weight in CTRL (+12 g; P<0. 01) and PF (+7 g; not significant) animals, growth was not stimulated in ZD rats (-1.5 g) in comparison with the corresponding untreated groups. However, circulating IGF-I and IGFBP-3 levels were restored by IGF-I infusion to levels similar to those in untreated CTRL rats. In conclusion, restoration of normal circulating levels of IGF-I and IGFBP-3 by rhIGF-I infusion fails to reverse the growth retardation induced by zinc deficiency. These results suggest that growth retardation related to zinc deficiency is not only caused by low serum IGF-I concentrations, but also by inhibition of the anabolic actions of IGF-I.

Analysis of Variance↗