Imbalanced Expression of IGF2 and PCSK4 Is Associated With Overproduction of Big IGF2 in SFT With NICTH : A Pilot Study
Context: Nonislet cell tumor hypoglycemia (NICTH) is a rare but serious paraneoplastic syndrome associated with large tumors. The high molecular weight IGF2, known as "big" IGF2, is produced by culprit tumors and leads to severe hypoglycemia. The detailed mechanism of its production in NICTH, however, remains unclear.
Objective: To clarify the mechanism of production of big IGF2 in light of the processing of pro-IGF2 in patients with solitary fibrous tumor (SFT) and NICTH.
Design: We enrolled 14 patients with SFT and divided them based on the presence or absence of hypoglycemia. In light of the processing of pro-IGF2 in SFT with hypoglycemia, we, retrospectively, compared the production levels of big IGF2 and the expression levels of IGF2 and proprotein convertase subtilisin/kexin type 4 (PCSK4), a proteolytic enzyme of pro-IGF2.
Results: In all patients with NICTH, big IGF2 was detected in serum by western immunoblotting analysis. Moreover, we showed that two patients without hypoglycemia also had a small amount of big IGF2 in their serum. By immunohistochemical analysis, the protein expression level of IGF2 was significantly higher in the NICTH group than in the non-NICTH group (P = 0.043). The IGF2/PCSK4 protein expression-level ratio in the NICTH group was significantly higher than that in the non-NICTH group (P = 0.021).
Conclusion: In patients with SFT and hypoglycemia, an imbalance of IGF2 and PCSK4 expression could lead to increased serum levels of big IGF2.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:103 |
|---|---|
| Enthalten in: |
The Journal of clinical endocrinology and metabolism - 103(2018), 7 vom: 01. Juli, Seite 2728-2734 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kawai, Shintaro [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
67763-97-7 |
|---|
| Anmerkungen: |
Date Completed 04.01.2019 Date Revised 10.12.2019 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1210/jc.2018-00593 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM285418408 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM285418408 | ||
| 003 | DE-627 | ||
| 005 | 20231225045413.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1210/jc.2018-00593 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0951.xml |
| 035 | |a (DE-627)NLM285418408 | ||
| 035 | |a (NLM)29897468 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kawai, Shintaro |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Imbalanced Expression of IGF2 and PCSK4 Is Associated With Overproduction of Big IGF2 in SFT With NICTH |b A Pilot Study |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.01.2019 | ||
| 500 | |a Date Revised 10.12.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Context: Nonislet cell tumor hypoglycemia (NICTH) is a rare but serious paraneoplastic syndrome associated with large tumors. The high molecular weight IGF2, known as "big" IGF2, is produced by culprit tumors and leads to severe hypoglycemia. The detailed mechanism of its production in NICTH, however, remains unclear | ||
| 520 | |a Objective: To clarify the mechanism of production of big IGF2 in light of the processing of pro-IGF2 in patients with solitary fibrous tumor (SFT) and NICTH | ||
| 520 | |a Design: We enrolled 14 patients with SFT and divided them based on the presence or absence of hypoglycemia. In light of the processing of pro-IGF2 in SFT with hypoglycemia, we, retrospectively, compared the production levels of big IGF2 and the expression levels of IGF2 and proprotein convertase subtilisin/kexin type 4 (PCSK4), a proteolytic enzyme of pro-IGF2 | ||
| 520 | |a Results: In all patients with NICTH, big IGF2 was detected in serum by western immunoblotting analysis. Moreover, we showed that two patients without hypoglycemia also had a small amount of big IGF2 in their serum. By immunohistochemical analysis, the protein expression level of IGF2 was significantly higher in the NICTH group than in the non-NICTH group (P = 0.043). The IGF2/PCSK4 protein expression-level ratio in the NICTH group was significantly higher than that in the non-NICTH group (P = 0.021) | ||
| 520 | |a Conclusion: In patients with SFT and hypoglycemia, an imbalance of IGF2 and PCSK4 expression could lead to increased serum levels of big IGF2 | ||
| 650 | 4 | |a Evaluation Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a IGF2 protein, human |2 NLM | |
| 650 | 7 | |a Insulin-Like Growth Factor II |2 NLM | |
| 650 | 7 | |a 67763-97-7 |2 NLM | |
| 650 | 7 | |a PCSK4 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.21.- |2 NLM | |
| 650 | 7 | |a Proprotein Convertases |2 NLM | |
| 650 | 7 | |a EC 3.4.21.- |2 NLM | |
| 650 | 7 | |a Subtilisins |2 NLM | |
| 650 | 7 | |a EC 3.4.21.- |2 NLM | |
| 700 | 1 | |a Ariyasu, Hiroyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Uraki, Shinsuke |e verfasserin |4 aut | |
| 700 | 1 | |a Takeshima, Ken |e verfasserin |4 aut | |
| 700 | 1 | |a Morita, Shuhei |e verfasserin |4 aut | |
| 700 | 1 | |a Inaba, Hidefumi |e verfasserin |4 aut | |
| 700 | 1 | |a Iwakura, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Doi, Asako |e verfasserin |4 aut | |
| 700 | 1 | |a Ohashi, Takuya |e verfasserin |4 aut | |
| 700 | 1 | |a Kawago, Mitsumasa |e verfasserin |4 aut | |
| 700 | 1 | |a Matsuoka, Naoki |e verfasserin |4 aut | |
| 700 | 1 | |a Okamura, Shintaro |e verfasserin |4 aut | |
| 700 | 1 | |a Tsujii, Satoru |e verfasserin |4 aut | |
| 700 | 1 | |a Akamizu, Takashi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of clinical endocrinology and metabolism |d 1945 |g 103(2018), 7 vom: 01. Juli, Seite 2728-2734 |w (DE-627)NLM00001821X |x 1945-7197 |7 nnns |
| 773 | 1 | 8 | |g volume:103 |g year:2018 |g number:7 |g day:01 |g month:07 |g pages:2728-2734 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1210/jc.2018-00593 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 103 |j 2018 |e 7 |b 01 |c 07 |h 2728-2734 | ||