Journal article
Chronic hyperinsulinemia increases myoblast proliferation in fetal sheep skeletal muscle
Endocrinology (Philadelphia), Vol.157(6), pp.2447-2460
06/01/2016
DOI: 10.1210/en.2015-1744
PMID: 27049667
Abstract
Insulin is an important fetal growth factor. However, chronic experimental hyperinsulinemia in the fetus fails to accelerate linear and lean mass growth beyond normal rates. Mechanisms preventing accelerated lean mass accretion during hyperinsulinemia are unknown. To address potential mechanisms, late-gestation fetal sheep were infused with iv insulin and glucose to produce euglycemic hyperinsulinemia (INS) or saline for 7–9 days. Fetal substrate uptake and protein metabolic rates were measured. INS fetuses had 1.5-fold higher insulin concentrations (P < .0001) and equivalent glucose concentrations. INS fetuses had 20% more Pax7+ nuclei in the biceps femoris, which indicates the potential for hyperinsulinemia to increase the number of myoblasts within late-gestation fetal skeletal muscle. Additionally, the percentage of Pax7+ myoblasts that expressed Ki-67 was 1.3-fold higher and expression of myogenic regulatory factors was 50% lower in INS fetuses (MYF5 and MYOG [myogenin], P < .005), which indicates a shift toward myoblast proliferation over differentiation. There were no differences for fetal body, organ, or muscle weights, although INS placentas weighed 28% less (P < .05). Protein synthesis and accretion rates did not change in INS fetuses, nor did fiber muscle size. Essential amino acid concentrations were lower in the INS group (P < .05) except for tryptophan. Umbilical blood flow, net total amino acids, and O2 uptakes rates did not differ between groups. Arterial O2 content was 33% lower (P < .005) and norepinephrine was 100% higher in the INS fetuses (P < .01), all of which are factors that may counteract fetal protein accretion during hyperinsulinemia despite an increase in myoblast proliferation.
Details
- Title: Subtitle
- Chronic hyperinsulinemia increases myoblast proliferation in fetal sheep skeletal muscle
- Creators
- Laura D. Brown - University of Colorado DenverStephanie R. Wesolowski - University of Colorado DenverJenai Kailey - University of Colorado DenverStephanie Bourque - University of Colorado DenverAveri Wilson - University of Colorado DenverSasha E. Andrews - University of Colorado DenverWilliam W. Hay - University of Colorado DenverPaul J. Rozance - University of Colorado Denver
- Resource Type
- Journal article
- Publication Details
- Endocrinology (Philadelphia), Vol.157(6), pp.2447-2460
- DOI
- 10.1210/en.2015-1744
- PMID
- 27049667
- NLM abbreviation
- Endocrinology
- ISSN
- 0013-7227
- eISSN
- 1945-7170
- Number of pages
- 14
- Grant note
- K12 HD057022 / National Institutes of Health KL2TR001080; TL1TR001081; UL1TR001082 / National Institutes of Health-National Center for Advancing Translational Sciences K01 DK090199; K08 HD060688; K12 HD057022; R01 DK088139; R01 HD079404-01A1; T32007186-32 / National Institutes of Health (http://data.elsevier.com/vocabulary/SciValFunders/100000002) Eunice Kennedy Shriver National Institute of Child Health and Human Development (http://data.elsevier.com/vocabulary/SciValFunders/100009633) R01 DK088139 / National Institutes of Health K12HD068372 / National Institute of Child Health and Human Development (http://data.elsevier.com/vocabulary/SciValFunders/100000071) Bill and Melinda Gates Foundation (http://data.elsevier.com/vocabulary/SciValFunders/100000865) National Institutes of Health (http://data.elsevier.com/vocabulary/SciValFunders/100000002) K08 HD060688 / National Institutes of Health OPP1061082 / Grand Challenges Exploration
- Language
- English
- Date published
- 06/01/2016
- Academic Unit
- Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9985123696302771
Metrics
1 Record Views