Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells.
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...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2017-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC5540605?pdf=render |
id |
doaj-e2e5c82717fb4d2dbb11a4a4ed9d934b |
---|---|
record_format |
Article |
spelling |
doaj-e2e5c82717fb4d2dbb11a4a4ed9d934b2020-11-25T01:49:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018119010.1371/journal.pone.0181190Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells.Nunzia CaporarelloCristina ParrinoVincenzo TrischittaLucia FrittittaGlucagon-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.http://europepmc.org/articles/PMC5540605?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nunzia Caporarello Cristina Parrino Vincenzo Trischitta Lucia Frittitta |
spellingShingle |
Nunzia Caporarello Cristina Parrino Vincenzo Trischitta Lucia Frittitta Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells. PLoS ONE |
author_facet |
Nunzia Caporarello Cristina Parrino Vincenzo Trischitta Lucia Frittitta |
author_sort |
Nunzia Caporarello |
title |
Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells. |
title_short |
Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells. |
title_full |
Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells. |
title_fullStr |
Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells. |
title_full_unstemmed |
Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells. |
title_sort |
insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2017-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC5540605?pdf=render |
work_keys_str_mv |
AT nunziacaporarello insulinreceptorsignalingandglucagonlikepeptide1effectsonpancreaticbetacells AT cristinaparrino insulinreceptorsignalingandglucagonlikepeptide1effectsonpancreaticbetacells AT vincenzotrischitta insulinreceptorsignalingandglucagonlikepeptide1effectsonpancreaticbetacells AT luciafrittitta insulinreceptorsignalingandglucagonlikepeptide1effectsonpancreaticbetacells |
_version_ |
1725003863129325568 |