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Attenuated glucose-stimulated insulin secretion during an acute IGF-1 LR3 infusion into fetal sheep does not persist in isolated islets

Published online by Cambridge University Press:  28 April 2023

Alicia White Open the ORCID record for Alicia White [Opens in a new window] ,
Jane Stremming ,
Laura D. Brown  and
Paul J. Rozance
Alicia White*
Affiliation:
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Jane Stremming
Affiliation:
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Laura D. Brown
Affiliation:
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Paul J. Rozance
Affiliation:
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
*
Corresponding Author: Alicia White, Perinatal Research Center, Department of Pediatrics, University of Colorado Anschutz Medical Campus, 13243 E 23rd Avenue, MS F441, Aurora, CO 80045, USA. Email: Alicia.2.White@cuanschutz.edu
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Abstract

Insulin-like growth factor-1 (IGF-1) is a critical fetal growth hormone that has been proposed as a therapy for intrauterine growth restriction. We previously demonstrated that a 1-week IGF-1 LR3 infusion into fetal sheep reduces in vivo and in vitro insulin secretion suggesting an intrinsic islet defect. Our objective herein was to determine whether this intrinsic islet defect was related to chronicity of exposure. We therefore tested the effects of a 90-min IGF-1 LR3 infusion on fetal glucose-stimulated insulin secretion (GSIS) and insulin secretion from isolated fetal islets. We first infused late gestation fetal sheep (n = 10) with either IGF-1 LR3 (IGF-1) or vehicle control (CON) and measured basal insulin secretion and in vivo GSIS utilizing a hyperglycemic clamp. We then isolated fetal islets immediately following a 90-min IGF-1 or CON in vivo infusion and exposed them to glucose or potassium chloride to measure in vitro insulin secretion (IGF-1, n = 6; CON, n = 6). Fetal plasma insulin concentrations decreased with IGF-1 LR3 infusion (P < 0.05), and insulin concentrations during the hyperglycemic clamp were 66% lower with IGF-1 LR3 infusion compared to CON (P < 0.0001). Insulin secretion in isolated fetal islets was not different based on infusion at the time of islet collection. Therefore, we speculate that while acute IGF-1 LR3 infusion may directly suppress insulin secretion, the fetal β-cell in vitro retains the ability to recover GSIS. This may have important implications when considering the long-term effects of treatment modalities for fetal growth restriction.

Keywords

fetusinsulin-like growth factorβ-cellglucose-stimulated insulin secretion
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 14 , Issue 3 , June 2023 , pp. 353 - 361
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Copyright
© The Author(s), 2023. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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