Activation of imidazoline receptor I2, and improved pancreatic β-cell function in human islets
Amisten, Stefan LU ; Duner, Pontus LU ; Asplund, Olof LU ; Mohammed Al-Amily, Israa LU ; Groop, Leif LU and Salehi, Albert LU
(2018)
In Journal of Diabetes and its Complications
32(9).
p.813-818
- Abstract
Aim: The impact of BL11282, an imidazoline receptor (NISCH) agonist, on potentiation of glucose-stimulated insulin secretion (GSIS) from isolated human non-diabetic (ND) and type 2 diabetic (T2D) islets was investigated. Methods: Analysis of mRNA was performed by RNA-sequencing and qPCR. Insulin and cAMP by RIA and ELISA respectively. Results: RNA-sequencing data revealed that NISCH is highly expressed in fat tissues, islets, liver and muscles, with eight detectable splice variants of transcripts in islets. NISCH had a positive correlation with GLP-1 (GLP1R) and GIP (GIPR) receptor transcripts. The expression of NISCH was confirmed by qPCR in human islets. NISCH and GLP1R were comparably higher expressed in mouse islets compared to... (More)
Aim: The impact of BL11282, an imidazoline receptor (NISCH) agonist, on potentiation of glucose-stimulated insulin secretion (GSIS) from isolated human non-diabetic (ND) and type 2 diabetic (T2D) islets was investigated. Methods: Analysis of mRNA was performed by RNA-sequencing and qPCR. Insulin and cAMP by RIA and ELISA respectively. Results: RNA-sequencing data revealed that NISCH is highly expressed in fat tissues, islets, liver and muscles, with eight detectable splice variants of transcripts in islets. NISCH had a positive correlation with GLP-1 (GLP1R) and GIP (GIPR) receptor transcripts. The expression of NISCH was confirmed by qPCR in human islets. NISCH and GLP1R were comparably higher expressed in mouse islets compared to human islets. GSIS was dose-dependently potentiated by BL11282 from incubated islets of ND and T2D human islet donors. The insulinotropic action of BL11282 was associated with increased cAMP. While the harmful effect of high glucose on reductive capacity of islet cells was enhanced by glibenclamide during long-term culture, it was counteracted by BL11282 or Bt2-cAMP. BL11282 also increased proliferation of INS-1 cells during long-time culture. Conclusion: Our data suggest that BL11282 potentiates GSIS by an action involving cAMP/PKA system and BL11282 could be an attractive insulinotropic and β-cell protective agent.
(Less)
- author
- Amisten, Stefan
LU
; Duner, Pontus
LU
; Asplund, Olof
LU
; Mohammed Al-Amily, Israa
LU
; Groop, Leif
LU
and Salehi, Albert
LU
- organization
- publishing date
- 2018-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cell function, G-protein coupled receptor, Second messenger, Signal
- in
- Journal of Diabetes and its Complications
- volume
- 32
- issue
- 9
- pages
- 813 - 818
- publisher
- Elsevier
- external identifiers
-
- scopus:85049460767
- pmid:29996974
- ISSN
- 1056-8727
- DOI
- 10.1016/j.jdiacomp.2018.06.010
- language
- English
- LU publication?
- yes
- id
- e9f4b327-05f6-435e-be34-5af87a1d80e5
- date added to LUP
- 2018-07-26 13:16:10
- date last changed
- 2024-06-24 17:23:04
@article{e9f4b327-05f6-435e-be34-5af87a1d80e5,
abstract = {{<p>Aim: The impact of BL11282, an imidazoline receptor (NISCH) agonist, on potentiation of glucose-stimulated insulin secretion (GSIS) from isolated human non-diabetic (ND) and type 2 diabetic (T2D) islets was investigated. Methods: Analysis of mRNA was performed by RNA-sequencing and qPCR. Insulin and cAMP by RIA and ELISA respectively. Results: RNA-sequencing data revealed that NISCH is highly expressed in fat tissues, islets, liver and muscles, with eight detectable splice variants of transcripts in islets. NISCH had a positive correlation with GLP-1 (GLP1R) and GIP (GIPR) receptor transcripts. The expression of NISCH was confirmed by qPCR in human islets. NISCH and GLP1R were comparably higher expressed in mouse islets compared to human islets. GSIS was dose-dependently potentiated by BL11282 from incubated islets of ND and T2D human islet donors. The insulinotropic action of BL11282 was associated with increased cAMP. While the harmful effect of high glucose on reductive capacity of islet cells was enhanced by glibenclamide during long-term culture, it was counteracted by BL11282 or Bt2-cAMP. BL11282 also increased proliferation of INS-1 cells during long-time culture. Conclusion: Our data suggest that BL11282 potentiates GSIS by an action involving cAMP/PKA system and BL11282 could be an attractive insulinotropic and β-cell protective agent.</p>}},
author = {{Amisten, Stefan and Duner, Pontus and Asplund, Olof and Mohammed Al-Amily, Israa and Groop, Leif and Salehi, Albert}},
issn = {{1056-8727}},
keywords = {{Cell function; G-protein coupled receptor; Second messenger; Signal}},
language = {{eng}},
number = {{9}},
pages = {{813--818}},
publisher = {{Elsevier}},
series = {{Journal of Diabetes and its Complications}},
title = {{Activation of imidazoline receptor I<sub>2</sub>, and improved pancreatic β-cell function in human islets}},
url = {{http://dx.doi.org/10.1016/j.jdiacomp.2018.06.010}},
doi = {{10.1016/j.jdiacomp.2018.06.010}},
volume = {{32}},
year = {{2018}},
}