Analysis of acid-labile subunit and its usefulness in pediatrics

Zaidman, Verónica

doi:10.5546/aap.2017.eng.391

Cited by 5 publications

(8 citation statements)

References 35 publications

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“…While insulin resistance is also present in DM1 patients (51, 52), an upregulation of IGFBP7 remains to be observed. Besides the IGFBPs, IGF1 can also bind to the ALS glycoprotein which is produced in the liver and serum (41). The main function of ALS is to extend the half-life of IGF-IGFBP complexes in the circulation to act on the IGF1R and IR (41, 42).…”

Section: Physiology Of Insulin Signalingmentioning

confidence: 99%

“…Besides the IGFBPs, IGF1 can also bind to the ALS glycoprotein which is produced in the liver and serum (41). The main function of ALS is to extend the half-life of IGF-IGFBP complexes in the circulation to act on the IGF1R and IR (41, 42). The ability of the IGFBPs 1–7 and ALS to modulate IGF and insulin action may provide a route toward the modulation of insulin and IGF signaling in DM1.…”

Section: Physiology Of Insulin Signalingmentioning

confidence: 99%

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Insulin Signaling as a Key Moderator in Myotonic Dystrophy Type 1

et al. 2019

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Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disease characterized by multi-system involvement. Affected organ system includes skeletal muscle, heart, gastro-intestinal system and the brain. In this review, we evaluate the evidence for alterations in insulin signaling and their relation to clinical DM1 features. We start by summarizing the molecular pathophysiology of DM1. Next, an overview of normal insulin signaling physiology is given, and evidence for alterations herein in DM1 is presented. Clinically, evidence for involvement of insulin signaling pathways in DM1 is based on the increased incidence of insulin resistance seen in clinical practice and recent trial evidence of beneficial effects of metformin on muscle function. Indirectly, further support may be derived from certain CNS derived symptoms characteristic of DM1, such as obsessive-compulsive behavior features, for which links with altered insulin signaling has been demonstrated in other diseases. At the basic scientific level, several pathophysiological mechanisms that operate in DM1 may compromise normal insulin signaling physiology. The evidence presented here reflects the importance of insulin signaling in relation to clinical features of DM1 and justifies further basic scientific and clinical, therapeutically oriented research.

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Section: Physiology Of Insulin Signalingmentioning

confidence: 99%

Section: Physiology Of Insulin Signalingmentioning

confidence: 99%

Insulin Signaling as a Key Moderator in Myotonic Dystrophy Type 1

et al. 2019

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“…Acid-labile subunit (ALS) is an 85 kDa glycoprotein, which is produced in the liver in response to growth hormone (GH) (1). The main role of ALS is to form a ternary complex with insulin-like growth factor 1 (IGF-1) and IGF binding proteins 3 or 5 (IGFBP-3 and IGFBP-5) in order to extend their circulating half-life from minutes to more than 12 hours (2).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Growth hormone is the main inducer of ALS synthesis in hepatocytes, therefore serum levels of ALS in GHD patients are quite reduced (1). Reduction of ALS serum levels is observed also in some conditions such as malnutrition, fasting, diabetes, catabolic diseases, and anorexia nervosa (1,4,8). Acid-labile subunit deficiency as a result of homozygous or heterozygous IGFALS gene mutations is characterized by very low serum levels of IGF-1 and especially IGFBP-3, normal or compensatory elevated levels of GH and clinical presentation of modest short stature (range -2 to -3 SD), delayed pubertal onset, insulin insensitivity, osteopenia and poor response to treatment with recombinant human GH (rhGH) (9,10).…”

Section: Introductionmentioning

confidence: 99%

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Screening for acid-labile subunit deficiency in patients with growth hormone deficiency at a tertiary pediatric endocrinology center

Rankova,

Shefket,

Tsochev

et al. 2022

SSM

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INTRODUCTION: Acid-labile subunit (ALS) is a glycoprotein, which is produced in the liver in response to growth hormone (GH), with its main role being the formation of a complex with insulin-like growth factor 1 (IGF-1) and IGF-binding-protein-3 (IGFBP-3) in order to extend their circulating half-life and thus support the action of GH. Acid-labile subunit-deficient patients are of research interest because of the unclear incidence of the condition among the short-statured population and the need of specific therapeutic approach. AIM: The aim of this study is to assess the prevalence of ALS deficiency in a cohort of patients with GH deficiency (GHD) followed up in a tertiary university pediatric endocrinology center. DESIGN:The study participants were 71 children (76% boys, age range 2-18 years), diagnosed with GHD by 2 standard GH-stimulation tests (max GH <10 ng/mL), on GH therapy, and at mean age at the time of collection of samples: 11.6±3.3 years. Blood serum samples were collected from each patient during the routine visits at the center, and then were stored frozen at -80℃ in 0.5 mL aliquots until analysis. RESULTS: Acid-labile subunit deficiency screening identified serum ALS levels with range from 2.2 to 60 mg/L, with a mean of 17.4±8.7 mg/L. The mean ALS levels were significantly lower than the published ones from subjects without short stature but close to the levels in the referred for GHD patients (6.5±4.8 mg/L). Very low ALS levels (<4.0 mg/L) were detected in 3 (4.2%) of the patients. The low ALS levels corresponded with low SDS height (-2.8±1.2) and low SDS IGF-1 (-1.4±1.0) before therapy. In one of the 3 patients, the ALS level (2.2 mg/L) was close to that in patients with IGFALS gene mutations (<1.0 mg/L). CONCLUSION:The present results show the prevalence of ALS deficiency in the current GH treated cohort and support the evidence that investigation of ALS levels could be helpful in the differential diagnosis of growth disorders.

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Current Insights into the Role of the Growth Hormone-Insulin-Like Growth Factor System in Short Children Born Small for Gestational Age

Renes¹,

Doorn

Hokken-Koelega

2019

Horm Res Paediatr

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Background: The reason for the insufficient catch-up growth seen in 10% of children born small for gestational age (SGA) is poorly understood. Disturbances in the growth hormone (GH) – insulin-like growth factor (IGF) axis might underlie this failure to show sufficient catch-up growth. Conclusion: This review summarizes insights gained in the molecular and (epi) genetic mechanisms of the GH-IGF axis in short children born SGA. The most notable anomalies of the IGF system are the lowered IGF-I levels in both cord blood and the placenta, and the increased expression of IGF-binding proteins (IGFBP)-1 and IGFBP-2, which inhibit IGF-I, in the placenta of SGA neonates. These observations suggest a decreased bioactivity of IGF-I in utero. IGF-I levels remain reduced in SGA children with short stature, as well as IGFBP-3 and acid-labile subunit levels. Proteolysis of IGFBP-3 appears to be increased.

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Analysis of acid-labile subunit and its usefulness in pediatrics

Cited by 5 publications

References 35 publications

Insulin Signaling as a Key Moderator in Myotonic Dystrophy Type 1

Insulin Signaling as a Key Moderator in Myotonic Dystrophy Type 1

Screening for acid-labile subunit deficiency in patients with growth hormone deficiency at a tertiary pediatric endocrinology center

Current Insights into the Role of the Growth Hormone-Insulin-Like Growth Factor System in Short Children Born Small for Gestational Age

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