Journal article
Fetal hyperglycemia acutely induces persistent insulin resistance in skeletal muscle
Journal of endocrinology, Vol.242(1), pp.M1-M15
07/2019
DOI: 10.1530/JOE-18-0455
PMID: 30444716
Abstract
Offspring exposed in utero to maternal diabetes exhibit long-lasting insulin resistance, though the initiating mechanisms have received minimal experimental attention. Herein, we show that rat fetuses develop insulin resistance after only 2-day continuous exposure to isolated hyperglycemia starting on gestational day 18. Hyperglycemia-induced reductions in insulin-induced AKT phosphorylation localized primarily to fetal skeletal muscle. The skeletal muscle of hyperglycemia-exposed fetuses also exhibited impaired in vivo glucose uptake. To address longer term impacts of this short hyperglycemic exposure, neonates were cross-fostered and examined at 21 days postnatal age. Offspring formerly exposed to 2 days late gestation hyperglycemia exhibited mild glucose intolerance with insulin signaling defects localized only to skeletal muscle. Fetal hyperglycemic exposure has downstream consequences which include hyperinsulinemia and relative uteroplacental insufficiency. To determine whether these accounted for induction of insulin resistance, we examined fetuses exposed to late gestational isolated hyperinsulinemia or uterine artery ligation. Importantly, 2 days of fetal hyperinsulinemia did not impair insulin signaling in murine fetal tissues and 21-day-old offspring exposed to fetal hyperinsulinemia had normal glucose tolerance. Similarly, fetal exposure to 2-day uteroplacental insufficiency did not perturb insulin-stimulated AKT phosphorylation in fetal rats. We conclude that fetal exposure to hyperglycemia acutely produces insulin resistance. As hyperinsulinemia and placental insufficiency have no such impact, this occurs likely via direct tissue effects of hyperglycemia. Furthermore, these findings show that skeletal muscle is uniquely susceptible to immediate and persistent insulin resistance induced by hyperglycemia.
Details
- Title: Subtitle
- Fetal hyperglycemia acutely induces persistent insulin resistance in skeletal muscle
- Creators
- Kok Lim Kua - Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAShanming Hu - Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAChunlin Wang - Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAJianrong Yao - Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USADiana Dang - Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAAlexander B Sawatzke - Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAJeffrey L Segar - Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAKai Wang - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USAAndrew W Norris - Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Journal of endocrinology, Vol.242(1), pp.M1-M15
- DOI
- 10.1530/JOE-18-0455
- PMID
- 30444716
- NLM abbreviation
- J Endocrinol
- ISSN
- 0022-0795
- eISSN
- 1479-6805
- Publisher
- Bioscientifica Ltd
- Alternative title
- Fetal hyperglycemia induces insulin resistance
- Language
- English
- Date published
- 07/2019
- Academic Unit
- Endocrinology and Diabetes; Stead Family Department of Pediatrics; Biostatistics; Biochemistry and Molecular Biology
- Record Identifier
- 9984024407302771
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