Imbalanced Expression of IGF2 and PCSK4 Is Associated With Overproduction of Big IGF2 in SFT With NICTH: A Pilot Study

Kawai, Shintaro; Hiroyuki, Ariyasu; Uraki, Shinsuke; Takeshima, Ken; Morita, Shuhei; Inaba, Hidefumi; Iwakura, Hiroshi; Doi, Asako; Ohashi, Takuya; Kawago, Mitsumasa; Matsuoka, Naoki; Okamura, Shintaro; Tsujii, Satoru; Akamizu, Takashi

doi:10.1210/jc.2018-00593

Cited by 12 publications

(18 citation statements)

References 23 publications

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“…Cleavage at different sites generates proteoforms of different molecular weights. Usually it is the 7.5 kDa protein that is considered to be the "mature" form of IGF-2 [7,54,106,109,110]. But in some studies [108,111], 14-15 kDa proteoforms are called "mature" IGF-2.…”

Section: Cleavagementioning

confidence: 99%

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Insulin-Like Growth Factor 2 As a Possible Neuroprotective Agent and Memory Enhancer—Its Comparative Expression, Processing and Signaling in Mammalian CNS

Beletskiy

Чеснокова

Bal

2021

IJMS

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A number of studies performed on rodents suggest that insulin-like growth factor 2 (IGF-2) or its analogs may possibly be used for treating some conditions like Alzheimer’s disease, Huntington’s disease, autistic spectrum disorders or aging-related cognitive impairment. Still, for translational research a comparative knowledge about the function of IGF-2 and related molecules in model organisms (rats and mice) and humans is necessary. There is a number of important differences in IGF-2 signaling between species. In the present review we emphasize species-specific patterns of IGF-2 expression in rodents, humans and some other mammals, using, among other sources, publicly available transcriptomic data. We provide a detailed description of Igf2 mRNA expression regulation and pre-pro-IGF-2 protein processing in different species. We also summarize the function of IGF-binding proteins. We describe three different receptors able to bind IGF-2 and discuss the role of IGF-2 signaling in learning and memory, as well as in neuroprotection. We hope that comprehensive understanding of similarities and differences in IGF-2 signaling between model organisms and humans will be useful for development of more effective medicines targeting IGF-2 receptors.

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Section: Cleavagementioning

confidence: 99%

“…A few products of incomplete pro-IGF-2 cleavageweighing from 8 to 18 kDa were registered in some experiments[35,36,106,112]. (c) Mature IGF-2 (1-67 aa) has a molecular weight of 7.5 kDa[7,54,106,109,110]. (d) 15 and 20 kDa IGF-2 proteoforms were found in rat dorsal hippocampus[108].…”

mentioning

confidence: 92%

Insulin-Like Growth Factor 2 As a Possible Neuroprotective Agent and Memory Enhancer—Its Comparative Expression, Processing and Signaling in Mammalian CNS

Beletskiy

Чеснокова

Bal

2021

IJMS

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“…Disruption in this system is associated with several diseases such as the aforementioned IUGR. In addition, abnormalities in PC4 expression have been indicated in cancer [86] and infertility [87,88]. Pro-IGF2 has also been shown to be a potent activator of IGF2 signaling in tumors [89].…”

Section: Post-translational Modification Of Igf2mentioning

confidence: 99%

“…The expression and production of mainly pro-IGF2 tumors can avoid the downregulation of IGF2Rmediated IGF2 signaling and promote cancer progression [89]. Indeed, the expression and secretion of pro-IGF2 instead of mature IGF2 seem to be mediated by the decreased expression of the PC4 protein, which is responsible for the cleavage of pro-IGF2 [86,91].…”

Section: Igf2 Signaling In Cancermentioning

confidence: 99%

Insulin-Like Growth Factor 2 in Physiology, Cancer, and Cancer Treatment

Röttgering¹,

Szuhai²

2019

obm genet

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Insulin-like growth factor 2 (IGF2) is a strong mitogenic peptide with an imprinted gene that is primarily involved in fetal development. It is highly expressed in the fetus where it is involved in fetal growth and tissue differentiation. However, postnatally, the expression of IGF2 decreases despite higher expression levels in the blood as compared with that of IGF1. In adults, the physiological function of IGF2 is poorly understood; however, the possibility of a metabolic function exists. Although the expression of IGF2 normally decreases in adults, it is overexpressed in a variety of cancers and associated with increased insulin-like growth factor 1 (IGF1R) receptor and insulin receptor (IR) activity. This subsequently increases the activity of downstream genes such as AKT, FOXO, and MAPK, resulting in enhanced proliferation, survival, and overall worse prognosis in patients overexpressing IGF2. As IGF1R activation has been found in several types of cancers, many different IGF1R-targeted therapies have been clinically evaluated, however, with only limited anti-cancer efficacy. In the present review, the physiological function of IGF2 will be outlined in relation to gene expression, imprinting, and signaling. Additionally, differences in physiological and aberrant signaling of IGF2 in cancer will be summarized.

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“…5,13 The lattermost type is known as non-islet cell tumor hypoglycemia (NICTH) and mostly caused by overexpression of partially processed pro-IGF-2 (big-IGF-2) due to impaired posttranscriptional processing of IGF-2. 12 IGF-2 is initially synthesized as pre-pro-IGF-2, which is converted to pro-IGF-2 by various convertases. 6,19 Normally, pro-IGF-2 is processed to mature IGF-2 (about 7.5 kDa) through several steps of degradation.…”

mentioning

confidence: 99%

Big Insulin-like Growth Factor 2–Producing Tumor in a Hypoglycemic Dog

et al. 2020

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A 10-year-old female Papillon dog that had previously developed a mammary tumor was admitted for treatment of a hypoglycemic attack. Blood examination showed severe hypoglycemia and decreased blood insulin concentration. Computed tomography indicated multiple tumors in the cranial and caudal lobes of the right lung. These tumors were resected surgically and diagnosed as pulmonary adenocarcinomas by histopathologic examination. Hypoglycemia was temporarily improved after the resection, but a hypoglycemic event occurred 2 months after the surgery. Immunohistochemistry of the tumor demonstrated the expression of insulin-like growth factor 2 in tumor cells. Western blot analysis revealed the expression of high-molecular-weight (big)–insulin-like growth factor 2 in the tumor region. Insulin-like growth factor 2 mRNA expression was also confirmed in the tumor using reverse transcription–polymerase chain reaction. These findings indicate the diagnosis of non–islet cell tumor-induced hypoglycemia caused by big-insulin-like growth factor 2 produced by the tumor in the dog. This report provides information on differentiating tumors that cause paraneoplastic hypoglycemia.

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Imbalanced Expression of IGF2 and PCSK4 Is Associated With Overproduction of Big IGF2 in SFT With NICTH: A Pilot Study

Abstract: In patients with SFT and hypoglycemia, an imbalance of IGF2 and PCSK4 expression could lead to increased serum levels of big IGF2.

Cited by 12 publications

References 23 publications

Insulin-Like Growth Factor 2 As a Possible Neuroprotective Agent and Memory Enhancer—Its Comparative Expression, Processing and Signaling in Mammalian CNS

Insulin-Like Growth Factor 2 As a Possible Neuroprotective Agent and Memory Enhancer—Its Comparative Expression, Processing and Signaling in Mammalian CNS

Insulin-Like Growth Factor 2 in Physiology, Cancer, and Cancer Treatment

Big Insulin-like Growth Factor 2–Producing Tumor in a Hypoglycemic Dog

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