Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Pontus Dunér

Assistant researcher

Default user image.

Activation of imidazoline receptor I2, and improved pancreatic β-cell function in human islets

Author

  • Stefan Amisten
  • Pontus Duner
  • Olof Asplund
  • Israa Mohammed Al-Amily
  • Leif Groop
  • Albert Salehi

Summary, in English

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.

Department/s

  • Islet cell physiology
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Genomics, Diabetes and Endocrinology
  • Diabetes - Islet Patophysiology

Publishing year

2018-09

Language

English

Pages

813-818

Publication/Series

Journal of Diabetes and its Complications

Volume

32

Issue

9

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Keywords

  • Cell function
  • G-protein coupled receptor
  • Second messenger
  • Signal

Status

Published

Research group

  • Islet cell physiology
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Genomics, Diabetes and Endocrinology
  • Diabetes - Islet Patophysiology

ISBN/ISSN/Other

  • ISSN: 1056-8727