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Glucagon-like peptide 1 protects microvascular endothelial cells by inactivating the PARP-1/iNOS/NO pathway

Fu-qiang Liu1, Xiang-li Zhang, Lei Gong

  • 1Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, Shandong, China.

Molecular and Cellular Endocrinology
|April 5, 2011
PubMed

Insights

Glucagon-like peptide-1 (GLP-1) protects mouse islet microvascular endothelial cells (MS-1) from oxidized low-density lipoprotein (oxLDL) induced apoptosis. GLP-1 inactivates the PARP-1/iNOS/NO pathway, offering potential in diabetes mellitus prevention.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Biology

Background:

  • Increasing evidence links Glucagon-like peptide-1 (GLP-1) activity to type 2 diabetes pathogenesis beyond glucose control.
  • Apoptosis of islet microvascular endothelial cells (IMECs) is implicated in diabetes development.
  • The precise anti-apoptotic intracellular signaling mechanisms of GLP-1 in IMECs remain incompletely understood.

Purpose of the Study:

  • To investigate whether GLP-1 exerts anti-apoptotic effects in mouse IMECs (MS-1 cells) exposed to oxidized low-density lipoprotein (oxLDL).
  • To determine if GLP-1 inactivates the poly(ADP-ribose) polymerase-1 (PARP-1)/inducible nitric oxide synthase (iNOS)/nitric oxide (NO) pathway.
  • To explore the potential involvement of GLP-1 receptor (GLP-1R)/cyclic adenosine monophosphate (cAMP) signaling.

Main Methods:

  • MTT assay to assess cell viability.
  • Measurement of intracellular nitric oxide (NO) activity and lipid peroxidation.
  • Assessment of antioxidant activities.
  • Western blot analysis for PARP-1, nitrotyrosine, and iNOS protein expression.
  • Quantification of GLP-1 receptor and cAMP levels.

Main Results:

  • GLP-1 pre-incubation significantly restored oxLDL-induced loss of MS-1 cell viability in a dose-dependent manner.
  • GLP-1 reduced intracellular NO activity, suppressed lipid peroxidation, and enhanced endogenous antioxidant activities.
  • GLP-1 treatment decreased MS-1 cell apoptosis and prevented the upregulation of PARP-1/nitrotyrosine and iNOS.
  • GLP-1 administration correlated with increased GLP-1 receptor expression and cAMP levels.

Conclusions:

  • GLP-1 effectively protects MS-1 cells against oxLDL-induced apoptosis.
  • The protective mechanism involves the inactivation of the PARP-1/iNOS/NO pathway.
  • These findings suggest a potential role for GLP-1 in preventing diabetes mellitus pathogenesis through its effects on IMEC survival.

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