Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand

Abstract When exposed to nutrient excess and insulin resistance, pancreatic β-cells undergo adaptive changes in order to maintain glucose homeostasis. The role that growth control genes, highly expressed in early pancreas development, might exert in programming β-cell plasticity in later life is a p...

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Autores principales:	Ionel Sandovici, Constanze M. Hammerle, Sam Virtue, Yurena Vivas-Garcia, Adriana Izquierdo-Lahuerta, Susan E. Ozanne, Antonio Vidal-Puig, Gema Medina-Gómez, Miguel Constância
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/418fc450d39f40d4b1305155c0e3ac81
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spelling	oai:doaj.org-article:418fc450d39f40d4b1305155c0e3ac812021-12-02T18:15:45ZAutocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand10.1038/s41598-021-87292-x2045-2322https://doaj.org/article/418fc450d39f40d4b1305155c0e3ac812021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87292-xhttps://doaj.org/toc/2045-2322Abstract When exposed to nutrient excess and insulin resistance, pancreatic β-cells undergo adaptive changes in order to maintain glucose homeostasis. The role that growth control genes, highly expressed in early pancreas development, might exert in programming β-cell plasticity in later life is a poorly studied area. The imprinted Igf2 (insulin-like growth factor 2) gene is highly transcribed during early life and has been identified in recent genome-wide association studies as a type 2 diabetes susceptibility gene in humans. Hence, here we investigate the long-term phenotypic metabolic consequences of conditional Igf2 deletion in pancreatic β-cells (Igf2 βKO) in mice. We show that autocrine actions of IGF2 are not critical for β-cell development, or for the early post-natal wave of β-cell remodelling. Additionally, adult Igf2 βKO mice maintain glucose homeostasis when fed a chow diet. However, pregnant Igf2 βKO females become hyperglycemic and hyperinsulinemic, and their conceptuses exhibit hyperinsulinemia and placentomegalia. Insulin resistance induced by congenital leptin deficiency also renders Igf2 βKO females more hyperglycaemic compared to leptin-deficient controls. Upon high-fat diet feeding, Igf2 βKO females are less susceptible to develop insulin resistance. Based on these findings, we conclude that in female mice, autocrine actions of β-cell IGF2 during early development determine their adaptive capacity in adult life.Ionel SandoviciConstanze M. HammerleSam VirtueYurena Vivas-GarciaAdriana Izquierdo-LahuertaSusan E. OzanneAntonio Vidal-PuigGema Medina-GómezMiguel ConstânciaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ionel Sandovici Constanze M. Hammerle Sam Virtue Yurena Vivas-Garcia Adriana Izquierdo-Lahuerta Susan E. Ozanne Antonio Vidal-Puig Gema Medina-Gómez Miguel Constância Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand
description	Abstract When exposed to nutrient excess and insulin resistance, pancreatic β-cells undergo adaptive changes in order to maintain glucose homeostasis. The role that growth control genes, highly expressed in early pancreas development, might exert in programming β-cell plasticity in later life is a poorly studied area. The imprinted Igf2 (insulin-like growth factor 2) gene is highly transcribed during early life and has been identified in recent genome-wide association studies as a type 2 diabetes susceptibility gene in humans. Hence, here we investigate the long-term phenotypic metabolic consequences of conditional Igf2 deletion in pancreatic β-cells (Igf2 βKO) in mice. We show that autocrine actions of IGF2 are not critical for β-cell development, or for the early post-natal wave of β-cell remodelling. Additionally, adult Igf2 βKO mice maintain glucose homeostasis when fed a chow diet. However, pregnant Igf2 βKO females become hyperglycemic and hyperinsulinemic, and their conceptuses exhibit hyperinsulinemia and placentomegalia. Insulin resistance induced by congenital leptin deficiency also renders Igf2 βKO females more hyperglycaemic compared to leptin-deficient controls. Upon high-fat diet feeding, Igf2 βKO females are less susceptible to develop insulin resistance. Based on these findings, we conclude that in female mice, autocrine actions of β-cell IGF2 during early development determine their adaptive capacity in adult life.
format	article
author	Ionel Sandovici Constanze M. Hammerle Sam Virtue Yurena Vivas-Garcia Adriana Izquierdo-Lahuerta Susan E. Ozanne Antonio Vidal-Puig Gema Medina-Gómez Miguel Constância
author_facet	Ionel Sandovici Constanze M. Hammerle Sam Virtue Yurena Vivas-Garcia Adriana Izquierdo-Lahuerta Susan E. Ozanne Antonio Vidal-Puig Gema Medina-Gómez Miguel Constância
author_sort	Ionel Sandovici
title	Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand
title_short	Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand
title_full	Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand
title_fullStr	Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand
title_full_unstemmed	Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand
title_sort	autocrine igf2 programmes β-cell plasticity under conditions of increased metabolic demand
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/418fc450d39f40d4b1305155c0e3ac81
work_keys_str_mv	AT ionelsandovici autocrineigf2programmesbcellplasticityunderconditionsofincreasedmetabolicdemand AT constanzemhammerle autocrineigf2programmesbcellplasticityunderconditionsofincreasedmetabolicdemand AT samvirtue autocrineigf2programmesbcellplasticityunderconditionsofincreasedmetabolicdemand AT yurenavivasgarcia autocrineigf2programmesbcellplasticityunderconditionsofincreasedmetabolicdemand AT adrianaizquierdolahuerta autocrineigf2programmesbcellplasticityunderconditionsofincreasedmetabolicdemand AT susaneozanne autocrineigf2programmesbcellplasticityunderconditionsofincreasedmetabolicdemand AT antoniovidalpuig autocrineigf2programmesbcellplasticityunderconditionsofincreasedmetabolicdemand AT gemamedinagomez autocrineigf2programmesbcellplasticityunderconditionsofincreasedmetabolicdemand AT miguelconstancia autocrineigf2programmesbcellplasticityunderconditionsofincreasedmetabolicdemand
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Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand

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