scholarly journals Insulin-like Growth Factor and its Therapeutic Potential for Diabetes Complications Mechanisms and Metabolic Links: A Review

2020 ◽  
Vol 16 (1) ◽  
pp. 24-34
Author(s):  
Belete Biadgo ◽  
Workineh Tamir ◽  
Sintayehu Ambachew
Keyword(s):  
Growth Factor ◽  
Diabetes Complications ◽  
Therapeutic Potential ◽  
Alternative Therapy ◽  
Vascular Complications ◽  
The Body ◽  
Insulin Like Growth Factor ◽  
Small Blood Vessel ◽  
Igf System ◽  
And Function

BACKGROUND: The insulin-like growth factor (IGF) system is an important system in normal physiological functioning of the body. In diabetes mellitus, alterations of IGF-binding protein (IGFBP) levels have been described, mainly in vascular complications. AIM: The aim of this review was to explore the role of the IGF system in reducing diabetes complications and its role as potential therapeutic target. RESULTS: IGF-1 plays a role in neuronal growth and developmental processes. Low concentrations of IGF-1 have been associated with neuropathy and other diabetes complications. Moreover, impaired IGF synthesis and function may result in cellular senescence and impaired vascular endothelial proliferation, adhesion, and integration. Of note, high IGF-1 bioavailability may prevent or delay the inception of diabetes-associated complications in diabetes patients. The mechanism of normal functioning IGF-1 is induced by increasing nitric oxide synthesis and potassium ion channel opening in cardiovascular physiology, which improves impaired small blood vessel function and reduces the occurrence of diabetes complications associated with reduced concentrations of IGF-1. CONCLUSIONS: IGF may be considered an alternative therapy for diabetes and diabetes-associated complications. Therefore, future studies should focus on the mechanism of action and therapeutic potential of IGFs in reducing the risk of development and progression of the disease in different clinical settings.

scholarly journals The Insulin-Like Growth Factor System

2003 ◽  
Vol 4 (4) ◽  
pp. 205-212 ◽  
Author(s):  
Derek Le Roith
Keyword(s):  
Growth Factor ◽  
Essential Role ◽  
Binding Proteins ◽  
The Body ◽  
Normal Adult ◽  
Insulin Like Growth Factor ◽  
Igf System ◽  
Major Player ◽  
Factor System

The insulin-like growth factor (IGF) system in ubiquitous and plays a role in every tissue of the body. It is comprised of ligands, receptors and binding proteins, each with specific functions. While it plays an essential role in embryonic and post-natal development, the IGF system is also important in normal adult physiology. There are now numerous examples of diseases such as diabetes, cancer, and malnutrition in which the IGF system is a major player and, not surprisingly, there are attempts to affect these disorders by manipulating the system.

Polycystic ovary syndrome and insulin-like growth factor (IGF) system.

2018 ◽  
Author(s):  
Ivica Lazurova ◽  
Jana Figurova ◽  
Zora Lazurova ◽  
Silvia Toporcerova ◽  
Miroslava Rabajdova ◽  
...  
Keyword(s):  
Growth Factor ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Insulin Like Growth Factor ◽  
Ovary Syndrome ◽  
Igf System

scholarly journals Insulin-Like Growth Factor Bioactivity, Stanniocalcin-2, Pregnancy-Associated Plasma Protein-A, and IGF-Binding Protein-4 in Pleural Fluid and Serum From Patients With Pulmonary Disease

2017 ◽  
Vol 102 (9) ◽  
pp. 3526-3534 ◽  
Author(s):  
Ulrick Skipper Espelund ◽  
Mette Bjerre ◽  
Rikke Hjortebjerg ◽  
Torben Riis Rasmussen ◽  
Anders Lundby ◽  
...  
Keyword(s):  
Growth Factor ◽  
Pleural Fluid ◽  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Insulin Like Growth Factor ◽  
Igf System ◽  
Igf Binding ◽  
Stanniocalcin 2 ◽  
Igf Binding Protein

Abstract Context Members of the insulin-like growth factor (IGF) system are primarily produced in the liver and secreted into the circulation, but they are also produced, recruited, and activated locally in tissues. Objective To compare activity and concentrations of IGF system components in pleural fluid and blood. Design Pathological pleural fluid, secondary to lung cancer or nonmalignant disease, and matching blood samples were collected from 24 patients ages 66.7 to 81.9 years. Methods IGF-related proteins and cytokine levels were measured by immunoassays or immunoblotting. Bioactive IGF was measured by an IGF-1 receptor phosphorylation assay. Results Total IGF-1 concentration did not differ between the compartments, but concentrations of free IGF-1 and bioactive IGF were more than threefold higher in pleural fluid than in corresponding serum samples (P = 0.0004), regardless of etiology. Median pregnancy-associated plasma protein-A (PAPP-A) and interleukin (IL)-6 levels were increased 47-fold and 143-fold, respectively, in pleural fluid compared with plasma (P < 0.0001). PAPP-A and IL-6 concentrations correlated positively (r = 0.46; P = 0.02). In pleural fluid, levels of PAPP-A–generated IGF binding protein-4 fragments correlated inversely with that of stanniocalcin-2 (r ≤ −0.42; P ≤ 0.05), a PAPP-A inhibitor; such correlations were absent in plasma. Conclusion Pathological pleural fluid is characterized by increased in vitro IGF bioactivity and elevated concentrations of PAPP-A, an IGF-activating proteinase. Thus, the tissue activity of the IGF system may differ substantially from that of the circulating IGF system. The correlation between IL-6 and PAPP-A indicates that inflammation plays a role in promoting local tissue IGF activity.

The Role of Auxologic and Growth Factor Measurements in the Diagnosis of Growth Hormone Deficiency

PEDIATRICS ◽  
1998 ◽  
Vol 102 (Supplement_3) ◽  
pp. 524-526
Author(s):  
Raymond L. Hintz
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
The Body ◽  
Hormone Deficiency ◽  
Insulin Like Growth Factor ◽  
Growth Study ◽  
Short Children ◽  
National Cooperative

The use of auxologic measurements in the diagnosis of short stature in children has a long history in pediatric endocrinology, and they have even been used as the primary criteria in selecting children for growth hormone (GH) therapy. Certainly, an abnormality in the control of growth is more likely in short children than in children of normal stature. However, most studies have shown little or no value of auxologic criteria in differentiating short children who have classic growth hormone deficiency (GHD) from short children who do not. In National Cooperative Growth Study Substudy VI, in more than 6000 children being assessed for short stature, the overall mean height SD score was −2.5 ± 1.1 and the body mass index standard deviation score was −0.5 ± 1.4. However, there were no significant differences in these measures between the patients who were found subsequently to have GHD and those who were not. There also was no consistent difference in the growth rates between the patients with classic GHD and those short children without a diagnosis of GHD. This probably reflects the fact that we are dealing with a selected population of children who were referred for short stature and are further selecting those who are the shortest for additional investigation. Growth factor measurements have been somewhat more useful in selecting patients with GHD and have been proposed as primary diagnostic criteria. However, in National Cooperative Growth Study Substudy VI, only small differences in the levels of insulin-like growth factor I and insulin-like growth factor binding protein 3 were seen between the patients who were selected for GH treatment and those who were not. Many studies indicate that the primary value of growth factor measurements is to exclude patients who are unlikely to have GHD or to identify those patients in whom an expedited work-up should be performed. The diagnosis of GHD remains difficult and must be based on all of the data possible and the best judgment of an experienced clinician. Even under ideal circumstances, errors of both overdiagnosis and underdiagnosis of GHD still are likely.

scholarly journals Determination of Alkali-Sensing Parts of the Insulin Receptor-Related Receptor Using the Bioinformatic Approach

Acta Naturae ◽  
2015 ◽  
Vol 7 (2) ◽  
pp. 80-86 ◽  
Author(s):  
I. E. Deyev ◽  
N. V. Popova ◽  
A. G. Petrenko
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Growth Factor Receptor ◽  
Ph Sensitive ◽  
Effective Concentration ◽  
The Body ◽  
Insulin Like Growth Factor ◽  
Extracellular Region ◽  
Half Maximal Effective Concentration ◽  
Receptor Family

IRR (insulin receptor-related receptor) is a receptor tyrosine kinase belonging to the insulin receptor family, which also includes insulin receptor and IGF-IR receptor. We have previously shown that IRR is activated by extracellular fluid with pH 7.9 and regulates excess alkali excretion in the body. We performed a bioinformatic analysis of the pH-sensitive potential of all three members of the insulin receptor family of various animal species (from frog to man) and their chimeras with swapping of different domains in the extracellular region. An analysis using the AcalPred program showed that insulin receptor family proteins are divided into two classes: one class with the optimal working pH in the acidic medium (virtually all insulin receptor and insulin-like growth factor receptor orthologs, except for the IGF-IR ortholog from Xenopus laevis) and the second class with the optimal working pH in the alkaline medium (all IRR orthologs). The program had predicted that the most noticeable effect on the pH-sensitive property of IRR would be caused by the replacement of the L1 and C domains in its extracellular region, as well as the replacement of the second and third fibronectin repeats. It had also been assumed that replacement of the L2 domain would have the least significant effect on the alkaline sensitivity of IRR. To test the in silico predictions, we obtained three constructs with swapping of the L1C domains, the third L2 domain, and all three domains L1CL2 of IRR with similar domains of the insulin-like growth factor receptor. We found that replacement of the L1C and L1CL2 domains reduces the receptors ability to be activated with alkaline pH, thus increasing the half-maximal effective concentration by about 100%. Replacement of the L2 domain increased the half-maximal effective concentration by 40%. Thus, our results indicate the high predictive potential of the AcalPred algorithm, not only for the pH-sensitive enzymes, but also for pH-sensitive receptors.

scholarly journals Insulin-Like Growth Factor-1: A Promising Therapeutic Target for Peripheral Nerve Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Benjamin R. Slavin ◽  
Karim A. Sarhane ◽  
Nicholas von Guionneau ◽  
Phillip J. Hanwright ◽  
Chenhu Qiu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Peripheral Nerve ◽  
Therapeutic Target ◽  
Surgical Repair ◽  
Therapeutic Potential ◽  
Regenerative Process ◽  
Insulin Like Growth Factor ◽  
Peripheral Nerve Injuries ◽  
Promising Therapeutic Target ◽  
Apoptotic Effects

Patients who sustain peripheral nerve injuries (PNIs) are often left with debilitating sensory and motor loss. Presently, there is a lack of clinically available therapeutics that can be given as an adjunct to surgical repair to enhance the regenerative process. Insulin-like growth factor-1 (IGF-1) represents a promising therapeutic target to meet this need, given its well-described trophic and anti-apoptotic effects on neurons, Schwann cells (SCs), and myocytes. Here, we review the literature regarding the therapeutic potential of IGF-1 in PNI. We appraised the literature for the various approaches of IGF-1 administration with the aim of identifying which are the most promising in offering a pathway toward clinical application. We also sought to determine the optimal reported dosage ranges for the various delivery approaches that have been investigated.

IGF-binding protein-2 is induced during development of urinary bladder hypertrophy in the diabetic rat

1997 ◽  
Vol 272 (2) ◽  
pp. E297-E303 ◽  
Author(s):  
Y. Chen ◽  
B. Gustafsson ◽  
H. J. Arnqvist
Keyword(s):  
Growth Factor ◽  
Urinary Bladder ◽  
Messenger Rna ◽  
Diabetic Rat ◽  
Insulin Like Growth Factor ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Streptozotocin Induced Diabetes ◽  
Wet Weight

Because the locally produced insulin-like growth factor-binding proteins (IGFBP) may influence bladder hypertrophy, either directly or by their interaction with insulin-like growth factor I (IGF-I), we studied the IGF system during the development of urinary bladder hypertrophy in rats with streptozotocin-induced diabetes. Messenger RNA for IGF-I, IGFBP-2, and IGFBP-4 was determined by solution hybridization. The bladder wet weight was elevated after 7 days. DNA synthesis was increased and peaked at 2 days, whereas DNA content per bladder wet weight was decreased by 7 days. The IGF-I mRNA did not change during the first 7 days and then decreased, and IGFBP-4 mRNA was increased transiently on day 7. On the other hand, IGFBP-2 mRNA was significantly increased after 1 day (2-fold), peaked by 7 days (6.4-fold), and then declined to approximately 50% above control at the end of experiment. This was associated with an increased IGFBP-2 protein content. Our results suggest that both stretching of the bladder due to diuresis and the diabetic state contribute to changes of the IGF system in the hypertrophying bladder.

scholarly journals A Novel Mutation in Insulin-Like Growth Factor 1 Receptor (c.641-2A>G) Is Associated with Impaired Growth, Hypoglycemia, and Modified Immune Phenotypes

2020 ◽  
Vol 93 (5) ◽  
pp. 322-334
Author(s):  
Melanie R. Shapiro ◽  
Timothy P. Foster ◽  
Daniel J. Perry ◽  
Ron G. Rosenfeld ◽  
Andrew Dauber ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mononuclear Cells ◽  
Phenotypic Expression ◽  
The Body ◽  
Mrna Splicing ◽  
Insulin Like Growth Factor ◽  
T Helper ◽  
Adaptive Immune Cells ◽  
Immune Phenotypes ◽  
Igf1r Expression

<b><i>Introduction:</i></b> Insulin-like growth factor 1 receptor (IGF1R) mutations lead to systemic disturbances in growth and glucose homeostasis due to widespread IGF1R expression throughout the body. IGF1R is expressed by innate and adaptive immune cells, facilitating their development and exerting immunomodulatory roles in the periphery. <b><i>Case Presentation:</i></b> We report on a family presenting with a novel heterozygous <i>IGF1R</i> mutation with characterization of the mutation, IGF1R expression, and immune phenotyping. Twin probands presented clinically with short stature and hypoglycemia. Variable phenotypic expression was seen in 2 other family members carrying the <i>IGF1R</i> mutation. The probands were treated with exogenous growth hormone therapy and dietary cornstarch, improving linear growth and reducing hypoglycemic events. <i>IGF1R</i> c.641-2A&#x3e;G caused abnormal mRNA splicing and premature protein termination. Flow cytometric immunophenotyping demonstrated lower IGF1R on peripheral blood mononuclear cells from <i>IGF1R</i> c.641-2A&#x3e;G subjects. This alteration was associated with reduced levels of T-helper 17 cells and a higher percentage of T-helper 1 cells compared to controls, suggesting decreased IGF1R expression may affect CD4<sup>+</sup> Th-cell lineage commitment. <b><i>Discussion:</i></b> Collectively, these data suggest a novel loss-of-function mutation (c.641-2A&#x3e;G) leads to aberrant mRNA splicing and IGF1R expression resulting in hypoglycemia, growth restriction, and altered immune phenotypes.

Sign in / Sign up

Export Citation Format

Share Document