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

DavidJ. Hill¹  NoelG. Morgan¹  MarkA. Russell²  SarahJ. Richardson²  Renee King³  JessicaL. Hill³  BrendaJ. Strutt³  Bibek Saha³  Yuzhen Tong³ 

[1] Clinical Science, University of Exeter Medical School, Exeter EX2 5DW, UK;;Institute of Biomedical &Lawson Health Research Institute, London, ON N6A 4V2, Canada;

关键词: β-cell;    mTOR;    insulin;    pancreas;    mouse;    low-protein;    glucagon;    STING;   

DOI  :  10.3390/nu11030605

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown