Nuclear PLCs affect insulin secretion by targeting PPARγ in pancreatic β cells

Roberta Fiume, Giulia Ramazzotti, Irene Faenza, Manuela Piazzi, Alberto Bavelloni, Anna Maria Billi, Lucio Cocco

Research output: Contribution to journalArticle

Abstract

Type 2 diabetes is a heterogeneous disorder caused by concomitant impairment of insulin secretion by pancreatic β cells and of insulin action in peripheral target tissues. Studies with inhibitors and agonists established a role for PLC in the regulation of insulin secretion but did not distinguish between effects due to nuclear or cytoplasmic PLC signaling pathways that act in a distinct fashion. We report that in MIN6 β cells, PLCβ1 localized in both nucleus and cytoplasm, PLCδ4 in the nucleus, and PLCγ1 in the cytoplasm. By silencing each isoform, we observed that they all affected glucose-induced insulin release both at basal and high glucose concentrations. To elucidate the molecular basis of PLC regulation, we focused on peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor transcription factor that regulates genes critical to β-cell maintenance and functions. Silencing of PLCβ1 and PLCδ4 resulted in a decrease in the PPARγ mRNA level. By means of a PPARγ- promoter-luciferase assay, the decrease could be attributed to a PLC action on the PPARγ-promoter region. The effect was specifically observed on silencing of the nuclear and not the cytoplasmic PLC. These findings highlight a novel pathway by which nuclear PLCs affect insulin secretion and identify PPARγ as a novel molecular target of nuclear PLCs.

Original languageEnglish
Pages (from-to)203-210
Number of pages8
JournalFASEB Journal
Volume26
Issue number1
DOIs
Publication statusPublished - Jan 2012

Fingerprint

Peroxisome Proliferator-Activated Receptors
Programmable logic controllers
Insulin
Cytoplasm
Glucose
Cytoplasmic and Nuclear Receptors
Luciferases
Genetic Promoter Regions
Type 2 Diabetes Mellitus
Protein Isoforms
Transcription Factors
Medical problems
Maintenance
Messenger RNA
Assays
Genes
Tissue

Keywords

  • Diabetes
  • Phosphoinositides
  • PLCβ1
  • PLCδ4

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Fiume, R., Ramazzotti, G., Faenza, I., Piazzi, M., Bavelloni, A., Billi, A. M., & Cocco, L. (2012). Nuclear PLCs affect insulin secretion by targeting PPARγ in pancreatic β cells. FASEB Journal, 26(1), 203-210. https://doi.org/10.1096/fj.11-186510

Nuclear PLCs affect insulin secretion by targeting PPARγ in pancreatic β cells. / Fiume, Roberta; Ramazzotti, Giulia; Faenza, Irene; Piazzi, Manuela; Bavelloni, Alberto; Billi, Anna Maria; Cocco, Lucio.

In: FASEB Journal, Vol. 26, No. 1, 01.2012, p. 203-210.

Research output: Contribution to journalArticle

Fiume, R, Ramazzotti, G, Faenza, I, Piazzi, M, Bavelloni, A, Billi, AM & Cocco, L 2012, 'Nuclear PLCs affect insulin secretion by targeting PPARγ in pancreatic β cells', FASEB Journal, vol. 26, no. 1, pp. 203-210. https://doi.org/10.1096/fj.11-186510
Fiume, Roberta ; Ramazzotti, Giulia ; Faenza, Irene ; Piazzi, Manuela ; Bavelloni, Alberto ; Billi, Anna Maria ; Cocco, Lucio. / Nuclear PLCs affect insulin secretion by targeting PPARγ in pancreatic β cells. In: FASEB Journal. 2012 ; Vol. 26, No. 1. pp. 203-210.
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