Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells

Nunzia Caporarello, Cristina Parrino, Vincenzo Trischitta, Lucia Frittitta

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Glucagon-like peptide-1 (GLP-1) is a potent gluco-incretin hormone, which plays a central role on pancreatic beta cell proliferation, survival and insulin secreting activity and whose analogs are used for treating hyperglycemia in type 2 diabetes mellitus. Notably, abnormal insulin signaling affects all the above-mentioned aspects on pancreatic beta cells. The aim of our study was to investigate whether the protective effects of GLP1-1 on beta cells are affected by altered insulin receptor signaling. To this end, several effects of GLP-1 were studied in INS-1E rat beta cells transfected either with an inhibitor of insulin receptor function (i.e., the Ectonucleotide Pyrophosphatase Phosphodiesterase 1, ENPP1), or with insulin receptor small interfering RNA, as well as in control cells. Crucial experiments were carried out also in a second cell line, namely the βTC-1 mouse beta cells. Our data indicate that in insulin secreting beta cells in which either ENPP1 was up-regulated or insulin receptor was down-regulated, GLP-1 positive effects on several pancreatic beta cell activities, including glucose-induced insulin secretion, cell proliferation and cell survival, were strongly reduced. Further studies are needed to understand whether such a scenario occurs also in humans and, if so, if it plays a role of clinical relevance in diabetic patients with poor responsiveness to GLP-1 related treatments.

Original languageEnglish
Article numbere0181190
JournalPLoS One
Volume12
Issue number8
DOIs
Publication statusPublished - Aug 1 2017

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glucagon-like peptide 1
Glucagon-Like Peptide 1
Insulin Receptor
islets of Langerhans
Insulin-Secreting Cells
Insulin
Cell proliferation
pyrophosphatases
insulin
Cell Survival
Cells
Cell Proliferation
cells
cell proliferation
Incretins
secretin
Medical problems
Hyperglycemia
Type 2 Diabetes Mellitus
Small Interfering RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells. / Caporarello, Nunzia; Parrino, Cristina; Trischitta, Vincenzo; Frittitta, Lucia.

In: PLoS One, Vol. 12, No. 8, e0181190, 01.08.2017.

Research output: Contribution to journalArticle

Caporarello, Nunzia ; Parrino, Cristina ; Trischitta, Vincenzo ; Frittitta, Lucia. / Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells. In: PLoS One. 2017 ; Vol. 12, No. 8.
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