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Article

Offspring of Mice Exposed to a Low-Protein Diet in Utero Demonstrate Changes in mTOR Signaling in Pancreatic Islets of Langerhans, Associated with Altered Glucagon and Insulin Expression and a Lower β-Cell Mass

1
Lawson Health Research Institute, London, ON N6A 4V2, Canada
2
Life Sciences Program, School of Interdisciplinary Science, McMaster University, Hamilton, ON L8S 4LD, Canada
3
Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter EX2 5DW, UK
4
Department of Physiology and Pharmacology, Western University, London, ON N6A 3K7, Canada
5
Department of Medicine, Western University, London, ON N6A 3K7, Canada
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2019, 11(3), 605; https://doi.org/10.3390/nu11030605
Received: 13 February 2019 / Revised: 4 March 2019 / Accepted: 5 March 2019 / Published: 12 March 2019
(This article belongs to the Special Issue Nutrition and Gestational Diabetes)
Low birth weight is a risk factor for gestational and type 2 diabetes (T2D). Since mammalian target of rapamycin (mTOR) controls pancreatic β-cell mass and hormone release, we hypothesized that nutritional insult in utero might permanently alter mTOR signaling. Mice were fed a low-protein (LP, 8%) or control (C, 20%) diet throughout pregnancy, and offspring examined until 130 days age. Mice receiving LP were born 12% smaller and β-cell mass was significantly reduced throughout life. Islet mTOR levels were lower in LP-exposed mice and localized predominantly to α-rather than β-cells. Incubation of isolated mouse islets with rapamycin significantly reduced cell proliferation while increasing apoptosis. mRNA levels for mTORC complex genes mTOR, Rictor and Raptor were elevated at 7 days in LP mice, as were the mTOR and Raptor proteins. Proglucagon gene expression was similarly increased, but not insulin or the immune/metabolic defense protein STING. In human and mouse pancreas STING was strongly associated with islet β-cells. Results support long-term changes in islet mTOR signaling in response to nutritional insult in utero, with altered expression of glucagon and insulin and a reduced β-cell mass. This may contribute to an increased risk of gestational or type 2 diabetes. View Full-Text
Keywords: β-cell; mTOR; insulin; pancreas; mouse; low-protein; glucagon; STING β-cell; mTOR; insulin; pancreas; mouse; low-protein; glucagon; STING
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MDPI and ACS Style

King, R.; Hill, J.L.; Saha, B.; Tong, Y.; Strutt, B.J.; Russell, M.A.; Morgan, N.G.; Richardson, S.J.; Hill, D.J. Offspring of Mice Exposed to a Low-Protein Diet in Utero Demonstrate Changes in mTOR Signaling in Pancreatic Islets of Langerhans, Associated with Altered Glucagon and Insulin Expression and a Lower β-Cell Mass. Nutrients 2019, 11, 605. https://doi.org/10.3390/nu11030605

AMA Style

King R, Hill JL, Saha B, Tong Y, Strutt BJ, Russell MA, Morgan NG, Richardson SJ, Hill DJ. Offspring of Mice Exposed to a Low-Protein Diet in Utero Demonstrate Changes in mTOR Signaling in Pancreatic Islets of Langerhans, Associated with Altered Glucagon and Insulin Expression and a Lower β-Cell Mass. Nutrients. 2019; 11(3):605. https://doi.org/10.3390/nu11030605

Chicago/Turabian Style

King, Renee, Jessica L. Hill, Bibek Saha, Yuzhen Tong, Brenda J. Strutt, Mark A. Russell, Noel G. Morgan, Sarah J. Richardson, and David J. Hill 2019. "Offspring of Mice Exposed to a Low-Protein Diet in Utero Demonstrate Changes in mTOR Signaling in Pancreatic Islets of Langerhans, Associated with Altered Glucagon and Insulin Expression and a Lower β-Cell Mass" Nutrients 11, no. 3: 605. https://doi.org/10.3390/nu11030605

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