Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Diabetologia
Published in: Diabetologia 6/2017

01-06-2017 | Short Communication

Conditional islet hypovascularisation does not preclude beta cell expansion during pregnancy in mice

Authors: Willem Staels, Yves Heremans, Gunter Leuckx, Naomi Van Gassen, Ciro Salinno, Sofie De Groef, Martine Cools, Eli Keshet, Yuval Dor, Harry Heimberg, Nico De Leu

Published in: Diabetologia | Issue 6/2017

Login to get access

Abstract

Aims/hypothesis

Endothelial–endocrine cell interactions and vascular endothelial growth factor (VEGF)-A signalling are deemed essential for maternal islet vascularisation, glucose control and beta cell expansion during mouse pregnancy. The aim of this study was to assess whether pregnancy-associated beta cell expansion was affected under conditions of islet hypovascularisation.

Methods

Soluble fms-like tyrosine kinase 1 (sFLT1), a VEGF-A decoy receptor, was conditionally overexpressed in maternal mouse beta cells from 1.5 to 14.5 days post coitum. Islet vascularisation, glycaemic control, beta cell proliferation, individual beta cell size and total beta cell volume were assessed in both pregnant mice and non-pregnant littermates.

Results

Conditional overexpression of sFLT1 in beta cells resulted in islet hypovascularisation and glucose intolerance in both pregnant and non-pregnant mice. In contrast to non-pregnant littermates, glucose intolerance in pregnant mice was transient. sFLT1 overexpression did not affect pregnancy-associated changes in beta cell proliferation, individual beta cell size or total beta cell volume.

Conclusions/interpretation

Reduced intra-islet VEGF-A signalling results in maternal islet hypovascularisation and impaired glycaemic control but does not preclude beta cell expansion during mouse pregnancy.
Appendix
Available only for authorised users
Literature
1.
Lammert E, Cleaver O, Melton D (2001) Induction of pancreatic differentiation by signals from blood vessels. Science 294:564–567CrossRefPubMed
2.
Yoshitomi H, Zaret KS (2004) Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Development 131:807–817CrossRefPubMed
3.
Lammert E, Gu G, McLaughlin M et al (2003) Role of VEGF-A in vascularization of pancreatic islets. Curr Biol 13:1070–1074CrossRefPubMed
4.
Nikolova G, Jabs N, Konstantinova I et al (2006) The vascular basement membrane: a niche for insulin gene expression and β cell proliferation. Dev Cell 10:397–405CrossRefPubMed
5.
D'Hoker J, De Leu N, Heremans Y et al (2013) Conditional hypovascularization and hypoxia in islets do not overtly influence adult beta-cell mass or function. Diabetes 62:4165–4173CrossRefPubMedPubMedCentral
6.
Parsons JA, Brelje TC, Sorenson RL (1992) Adaptation of islets of Langerhans to pregnancy: increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion. Endocrinology 130:1459–1466PubMed
7.
May D, Gilon D, Djonov V et al (2008) Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation. Proc Natl Acad Sci U S A 105:282–287CrossRefPubMed
8.
Shibuya M (2006) Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): a dual regulator for angiogenesis. Angiogenesis 9:225–230CrossRefPubMed
9.
Oropeza D, Jouvet N, Budry L et al (2015) Phenotypic characterization of MIP-CreERT1Lphi mice with transgene-driven islet expression of human growth hormone. Diabetes 64:3798–3807CrossRefPubMedPubMedCentral
10.
Brouwers B, de Faudeur G, Osipovich AB et al (2014) Impaired islet function in commonly used transgenic mouse lines due to human growth hormone minigene expression. Cell Metab 20:979–990CrossRefPubMed
11.
Schindelin J, Arganda-Carreras I, Frise E et al (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676–682CrossRefPubMed
12.
Coppens V, Heremans Y, Leuckx G et al (2013) Human blood outgrowth endothelial cells improve islet survival and function when co-transplanted in a mouse model of diabetes. Diabetologia 56:382–390CrossRefPubMed
13.
14.
Brissova M, Aamodt K, Brahmachary P et al (2014) Islet microenvironment, modulated by vascular endothelial growth factor-a signaling, promotes beta cell regeneration. Cell Metab 19:498–511CrossRefPubMedPubMedCentral
15.
Cantley J, Grey ST, Maxwell PH, Withers DJ (2010) The hypoxia response pathway and β-cell function. Diabetes Obes Metab 12:159–167CrossRefPubMed
16.
Kragl M, Schubert R, Karsjens H et al (2016) The biomechanical properties of an epithelial tissue determine the location of its vasculature. Nat Commun 7:13560CrossRefPubMedPubMedCentral
17.
Rieck S, Kaestner KH (2010) Expansion of beta-cell mass in response to pregnancy. Trends Endocrinol Metab 21:151–158CrossRefPubMed
18.
Johansson M, Mattsson G, Andersson A, Jansson L, Carlsson PO (2006) Islet endothelial cells and pancreatic beta-cell proliferation: studies in vitro and during pregnancy in adult rats. Endocrinology 147:2315–2324CrossRefPubMed
19.
Banerjee RR, Cyphert HA, Walker EM et al (2016) Gestational diabetes mellitus from inactivation of prolactin receptor and MafB in islet beta-cells. Diabetes 65:2331–2341CrossRefPubMed
20.
Metadata
Title
Conditional islet hypovascularisation does not preclude beta cell expansion during pregnancy in mice
Authors
Willem Staels
Yves Heremans
Gunter Leuckx
Naomi Van Gassen
Ciro Salinno
Sofie De Groef
Martine Cools
Eli Keshet
Yuval Dor
Harry Heimberg
Nico De Leu
Publication date
01-06-2017
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 6/2017
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-017-4243-1

Other articles of this Issue 6/2017

Diabetologia 6/2017 Go to the issue

Article

Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium

Article

Late-onset islet autoimmunity in childhood: the Diabetes Autoimmunity Study in the Young (DAISY)

Article

Cognitive deficits associated with impaired awareness of hypoglycaemia in type 1 diabetes

Article

Small-fibre neuropathy in men with type 1 diabetes and erectile dysfunction: a cross-sectional study

Article

Predicting hospital stay, mortality and readmission in people admitted for hypoglycaemia: prognostic models derivation and validation

Up front

Up front
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits