Imidazoline compounds protect against interleukin 1β-induced β-cell apoptosis

Sergei V. Zaitsev, Ioulia B. Appelskog, Iouri L. Kapelioukh, Shao Nian Yang, Martin Köhler, Suad Efendic, Per Olof Berggren

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Imidazoline compounds have been considered for the treatment of type 2 diabetes. We have now investigated the effects of imidazolines on interleukin (IL)-1β-induced β-cell apoptosis and the signal transduction pathways involved. Inhibition of Ca2+ influx into β-cells by D-600, a blocker of voltage-gated L-type Ca2+ channels, suppressed IL-1β-induced apoptosis. Our data show that calcineurin, Ca2+/calmodulin-dependent serine/threonine protein phosphatase 2B, is responsible for the effect of Ca2+ on β-cell apoptosis. We also demonstrate that IL-1β-mediated apoptosis correlates with expression of inducible nitric oxide synthase (iNOS) and the increase in intracellular production of nitric oxide. An inhibitor of cGMP-dependent protein kinase (PKG), KT5823, suppressed IL-1β-induced apoptosis, suggesting the involvement of a PKG-dependent pathway in the apoptotic process. One of the major findings in this study is that imidazoline compounds RX871024 and efaroxan, suggested as prototypes of a new generation of drugs against type 2 diabetes, can protect against IL-1β-induced apoptosis in pancreatic β-cells, possibly by their inhibition of the expression of iNOS, a key element in the IL-1β-induced apoptotic pathway in pancreatic β-cells. These data suggest that imidazoline compounds should be explored as a potential therapeutic agent for the treatment of both type 1 and type 2 diabetes.

Original languageEnglish
JournalDiabetes
Volume50
Issue numberSUPPL. 1
StatePublished - Feb 22 2001
Externally publishedYes

Fingerprint

Imidazolines
Interleukin-1
Apoptosis
Type 2 Diabetes Mellitus
efaroxan
Calcineurin
Nitric Oxide Synthase Type II
Gallopamil
Cyclic GMP-Dependent Protein Kinases
Threonine
Calmodulin
Type 1 Diabetes Mellitus
Serine
Signal Transduction
Nitric Oxide
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Zaitsev, S. V., Appelskog, I. B., Kapelioukh, I. L., Yang, S. N., Köhler, M., Efendic, S., & Berggren, P. O. (2001). Imidazoline compounds protect against interleukin 1β-induced β-cell apoptosis. Diabetes, 50(SUPPL. 1).

Imidazoline compounds protect against interleukin 1β-induced β-cell apoptosis. / Zaitsev, Sergei V.; Appelskog, Ioulia B.; Kapelioukh, Iouri L.; Yang, Shao Nian; Köhler, Martin; Efendic, Suad; Berggren, Per Olof.

In: Diabetes, Vol. 50, No. SUPPL. 1, 22.02.2001.

Research output: Contribution to journalArticle

Zaitsev, SV, Appelskog, IB, Kapelioukh, IL, Yang, SN, Köhler, M, Efendic, S & Berggren, PO 2001, 'Imidazoline compounds protect against interleukin 1β-induced β-cell apoptosis', Diabetes, vol. 50, no. SUPPL. 1.
Zaitsev SV, Appelskog IB, Kapelioukh IL, Yang SN, Köhler M, Efendic S et al. Imidazoline compounds protect against interleukin 1β-induced β-cell apoptosis. Diabetes. 2001 Feb 22;50(SUPPL. 1).
Zaitsev, Sergei V. ; Appelskog, Ioulia B. ; Kapelioukh, Iouri L. ; Yang, Shao Nian ; Köhler, Martin ; Efendic, Suad ; Berggren, Per Olof. / Imidazoline compounds protect against interleukin 1β-induced β-cell apoptosis. In: Diabetes. 2001 ; Vol. 50, No. SUPPL. 1.
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