Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell Regeneration
Progressive loss and dysfunction of islet β-cells has not yet been solved in the treatment of diabetes. Regenerating protein (Reg) has been identified as a trophic factor which is demonstrated to be associated with pancreatic tissue regeneration. We previously produced recombinant Reg3α protein (rReg3α) and proved that it protects against acute pancreatitis in mice. Whether rReg3α protects islet β-cells in diabetes has been elusive. In the present study, rReg3α stimulated MIN6 cell proliferation and resisted STZ-caused cell death. The protective effect of rReg3α was also found in mouse primary islets. In BALB/c mice, rReg3α administration largely alleviated STZ-induced diabetes by the preservation of β-cell mass. The protective mechanism could be attributed to Akt/Bcl-2/-xL activation and GRP78 upregulation. Scattered insulin-expressing cells and clusters with small size, low insulin density, and exocrine distribution were observed and considered to be neogenic. In isolated acinar cells with wheat germ agglutinin (WGA) labeling, rReg3α treatment generated insulin-producing cells through Stat3/Ngn3 signaling, but these cells were not fully functional in response to glucose stimulation. Our results demonstrated that rReg3α resists STZ-induced β-cell death and promotes β-cell regeneration. rReg3α could serve as a potential drug for β-cell maintenance in anti-diabetic treatment.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2022 |
---|---|
Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
---|---|
Enthalten in: |
International journal of molecular sciences - 23(2022), 18 vom: 13. Sept. |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Yu, Luting [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 26.09.2022 Date Revised 28.09.2022 published: Electronic Citation Status MEDLINE |
---|
doi: |
10.3390/ijms231810584 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM346588707 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM346588707 | ||
003 | DE-627 | ||
005 | 20231226031822.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3390/ijms231810584 |2 doi | |
028 | 5 | 2 | |a pubmed24n1155.xml |
035 | |a (DE-627)NLM346588707 | ||
035 | |a (NLM)36142497 | ||
035 | |a (PII)10584 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Yu, Luting |e verfasserin |4 aut | |
245 | 1 | 0 | |a Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell Regeneration |
264 | 1 | |c 2022 | |
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 26.09.2022 | ||
500 | |a Date Revised 28.09.2022 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Progressive loss and dysfunction of islet β-cells has not yet been solved in the treatment of diabetes. Regenerating protein (Reg) has been identified as a trophic factor which is demonstrated to be associated with pancreatic tissue regeneration. We previously produced recombinant Reg3α protein (rReg3α) and proved that it protects against acute pancreatitis in mice. Whether rReg3α protects islet β-cells in diabetes has been elusive. In the present study, rReg3α stimulated MIN6 cell proliferation and resisted STZ-caused cell death. The protective effect of rReg3α was also found in mouse primary islets. In BALB/c mice, rReg3α administration largely alleviated STZ-induced diabetes by the preservation of β-cell mass. The protective mechanism could be attributed to Akt/Bcl-2/-xL activation and GRP78 upregulation. Scattered insulin-expressing cells and clusters with small size, low insulin density, and exocrine distribution were observed and considered to be neogenic. In isolated acinar cells with wheat germ agglutinin (WGA) labeling, rReg3α treatment generated insulin-producing cells through Stat3/Ngn3 signaling, but these cells were not fully functional in response to glucose stimulation. Our results demonstrated that rReg3α resists STZ-induced β-cell death and promotes β-cell regeneration. rReg3α could serve as a potential drug for β-cell maintenance in anti-diabetic treatment | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a GRP78 | |
650 | 4 | |a diabetes | |
650 | 4 | |a regenerating protein | |
650 | 4 | |a the islets | |
650 | 4 | |a β-cell regeneration | |
650 | 7 | |a Insulin |2 NLM | |
650 | 7 | |a Insulins |2 NLM | |
650 | 7 | |a Proto-Oncogene Proteins c-bcl-2 |2 NLM | |
650 | 7 | |a Recombinant Proteins |2 NLM | |
650 | 7 | |a Wheat Germ Agglutinins |2 NLM | |
650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
650 | 7 | |a EC 2.7.11.1 |2 NLM | |
650 | 7 | |a Glucose |2 NLM | |
650 | 7 | |a IY9XDZ35W2 |2 NLM | |
700 | 1 | |a Li, Liang |e verfasserin |4 aut | |
700 | 1 | |a Liu, Junli |e verfasserin |4 aut | |
700 | 1 | |a Sun, Hao |e verfasserin |4 aut | |
700 | 1 | |a Li, Xiang |e verfasserin |4 aut | |
700 | 1 | |a Xiao, Hanyu |e verfasserin |4 aut | |
700 | 1 | |a Alfred, Martin Omondi |e verfasserin |4 aut | |
700 | 1 | |a Wang, Min |e verfasserin |4 aut | |
700 | 1 | |a Wu, Xuri |e verfasserin |4 aut | |
700 | 1 | |a Gao, Yan |e verfasserin |4 aut | |
700 | 1 | |a Luo, Chen |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 23(2022), 18 vom: 13. Sept. |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
773 | 1 | 8 | |g volume:23 |g year:2022 |g number:18 |g day:13 |g month:09 |
856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms231810584 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 23 |j 2022 |e 18 |b 13 |c 09 |