Low birth weight and poor foetal growth following low protein (LP) exposure are associated with altered islet development and glucose intolerance in adulthood. Additionally, LP-fed offspring fail to regenerate their β-cells following depletion with streptozotocin (STZ) in contrast to control-fed offspring that restore β-cell mass. Our objective was to identify signalling pathways and cellular functions that may be critically altered in LP offspring rendering them susceptible to developing long-term glucose intolerance and decreased β-cell plasticity. Pregnant Balb/c mice were fed a control (C; 20% protein) or an isocaloric LP (8% protein) diet throughout gestation and C diet thereafter. Female offspring were injected intraperitoneally with 35 mg/kg STZ or vehicle on days 1 to 5 for each dietary treatment. At 30 days of age, total RNA was extracted from pancreatic tissue for microarray analysis using the Affymetrix GeneChip Mouse Genome 430 2.0. Gene and protein expression were quantified from isolated islets. Finally, β-cell proliferation was determined in vitro following REG1α treatment. The microarray data and GO enrichment analysis indicated that foetal protein restriction alters the early expression of genes necessary for many cell functions, such as oxidative phosphorylation and free radical scavenging. Expression of Reg1 was upregulated following STZ, whereas protein content was decreased in LP + STZ islets. Furthermore, REG1α failed to stimulate β-cell proliferation in vitro in LP + STZ islets. Therefore, early nutritional insults may programme the Reg1 pathway resulting in a limited ability to increase β-cell mass during metabolic stress. In conclusion, this study implicates the Reg1 pathway in β-cell regeneration and describes altered programming of gene expression in LP offspring, which underlies later development of cell dysfunction and glucose intolerance in adulthood.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1177/1535370213493715 | DOI Listing |
Biosci Biotechnol Biochem
January 2025
Division of Food Science and Biotechnology, Graduated School of Science and Technology, Shinshu University, 8304 Minami-minowa, Kamiina, Nagano, Japan.
Food-derived polyphenols and some alkaloids have reported bioactivities related the prevention of systemic metabolic disorders such as obesity, glucose intolerance, and dyslipidemia. For food-derived components to exert their functions in vivo, it is essential the interaction with biological factors such as proteins, lipids, and nucleic acids. However, it is still unclear whether bioactive components in foods express functions related to their target factors.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Department of Anatomy, Chonnam National University Medical School, Hwasun 58128, Republic of Korea; Biomedical Science Graduate Program (BMSGP), Chonnam National University, Hwasun 58128, Republic of Korea. Electronic address:
Obesity is a prevalent metabolic disorder linked to insulin resistance, hyperglycemia, increased adiposity, chronic inflammation, and cognitive dysfunction. Recent research has focused on developing therapeutic strategies to mitigate cognitive impairment associated with obesity. Insulin growth factor-1 (IGF1) deficiency is linked to insulin resistance, glucose intolerance, and the progression of obesity-related central nervous system (CNS) disorders.
View Article and Find Full Text PDFDiabetes Obes Metab
January 2025
BFA, UMR 8251, CNRS, Team « Biologie et Pathologie du Pancréas Endocrine », Université Paris Cité, Paris, France.
Aims: Down syndrome (DS) or trisomy 21 is the most prevalent genetic disorder in the world. In addition to common symptoms such as intellectual disabilities and morphological abnormalities, several comorbidities are associated with DS, including metabolic dysfunction. Obesity and diabetes are more prevalent in people with DS compared with the general population.
View Article and Find Full Text PDFReprod Toxicol
January 2025
Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address:
Saturated fat has been linked to cardiovascular diseases, leading to an increase in polyunsaturated fat consumption. The aim of the present study was to investigate the effects of three fat sources (coconut oil, lard and soybean oil) on metabolic and reproductive parameters in heterogenic mice. Female Swiss mice (5-6 weeks old; n=9/group) were divided into four experimental groups: control (CC), coconut oil (CO), lard (LA), and soybean oil (SO), and were orally given 0.
View Article and Find Full Text PDFJ Steroid Biochem Mol Biol
January 2025
Department of endocrinology, the Second People's Hospital of Kunming, Kunming 650203, Yunnan, PR China. Electronic address:
The disorders of glucose and lipid metabolism contribute to severe diseases, including cardiovascular disease, diabetes, and fatty liver. Here, we identified DNA damage-binding protein 2 (DDB2), an E3 ubiquitin ligase, as a pivotal regulator of lipid metabolism disorders in type II diabetes mellitus (T2DM). A mouse model of T2DM and primary mouse hepatocytes with steatosis were induced.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!