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Pulsatile hyperglycemia increases insulin secretion but not pancreatic β-cell mass in intrauterine growth-restricted fetal sheep

Part of: DOHaD on International Women's Day 2020

Published online by Cambridge University Press:  05 July 2018

B. H. Boehmer Open the ORCID record for B. H. Boehmer [Opens in a new window] ,
L. D. Brown ,
S. R. Wesolowski ,
W. W. Hay Jr  and
P. J. Rozance
B. H. Boehmer
Affiliation:
Department of Pediatrics, Perinatal Research Center, University of Colorado School of Medicine, Aurora, CO, USA
L. D. Brown
Affiliation:
Department of Pediatrics, Perinatal Research Center, University of Colorado School of Medicine, Aurora, CO, USA
S. R. Wesolowski
Affiliation:
Department of Pediatrics, Perinatal Research Center, University of Colorado School of Medicine, Aurora, CO, USA
W. W. Hay Jr
Affiliation:
Department of Pediatrics, Perinatal Research Center, University of Colorado School of Medicine, Aurora, CO, USA
P. J. Rozance*
Affiliation:
Department of Pediatrics, Perinatal Research Center, University of Colorado School of Medicine, Aurora, CO, USA
*
Address for correspondence: P. J. Rozance, Perinatal Research Facility, University of Colorado Denver, 13243 E. 23rd Ave., MS F441, Aurora, CO 80045, USA. E-mail: [email protected]
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Abstract

Impaired β-cell development and insulin secretion are characteristic of intrauterine growth-restricted (IUGR) fetuses. In normally grown late gestation fetal sheep pancreatic β-cell numbers and insulin secretion are increased by 7–10 days of pulsatile hyperglycemia (PHG). Our objective was to determine if IUGR fetal sheep β-cell numbers and insulin secretion could also be increased by PHG or if IUGR fetal β-cells do not have the capacity to respond to PHG. Following chronic placental insufficiency producing IUGR in twin gestation pregnancies (n=7), fetuses were administered a PHG infusion, consisting of 60 min, high rate, pulsed infusions of dextrose three times a day with an additional continuous, low-rate infusion of dextrose to prevent a decrease in glucose concentrations between the pulses or a control saline infusion. PHG fetuses were compared with their twin IUGR fetus, which received a saline infusion for 7 days. The pulsed glucose infusion increased fetal arterial glucose concentrations an average of 83% during the infusion. Following the 7-day infusion, a square-wave fetal hyperglycemic clamp was performed in both groups to measure insulin secretion. The rate of increase in fetal insulin concentrations during the first 20 min of a square-wave hyperglycemic clamp was 44% faster in the PHG fetuses compared with saline fetuses (P<0.05). There were no differences in islet size, the insulin+ area of the pancreas and of the islets, and β-cell mass between groups (P>0.23). Chronic PHG increases early phase insulin secretion in response to acute hyperglycemia, indicating that IUGR fetal β-cells are functionally responsive to chronic PHG.

Keywords

β-cellfetushyperglycemiainsulinisletIUGR
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 5 , October 2018 , pp. 492 - 499
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

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