ArticleDiabetologia2018
Early deficits in insulin secretion, beta cell mass and islet blood perfusion precede onset of autoimmune type 1 diabetes in BioBreeding rats.
Article in Diabetologia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Quantitative temporal analysis of pancreatic islet T lymphocyte and macrophage infiltration heralded by serum IgE in congenic BioBreeding (BB) Gimap5Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Illuminating the complete ß-cell mass of the human pancreas- signifying a new view on the islets of Langerhans.Nature communications · 2024Article
- Analysis of the relationship between GLUT family in the progression and immune infiltration of head and neck squamous carcinoma.Diagnostic pathology · 2023Article
- Metabolic Role of GABA in the Secretory Function of Pancreatic β-Cells: Its Hypothetical Implication in β-Cell Degradation in Type 2 Diabetes.Metabolites · 2023Review
- Preclinical models for Type 1 Diabetes Mellitus - A practical approach for research.International journal of medical sciences · 2023Review
- Postnatal maturation of calcium signaling in islets of Langerhans from neonatal mice.Cell calcium · 2021Article
- Mesoscopic Optical Imaging of the Pancreas-Revisiting Pancreatic Anatomy and Pathophysiology.Frontiers in endocrinology · 2021Review
- Pregestational diet transition to normal-fat diet avoids the deterioration of pancreatic β-cell function in male offspring induced by maternal high-fat diet.The Journal of nutritional biochemistry · 2020Article
- Sugar-Lowering Drugs for Type 2 Diabetes Mellitus and Metabolic Syndrome-Strategies for In Vivo Administration: Part-II.Journal of clinical medicine · 2019Review
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisGenetic studies show coupling of genes affecting beta cell function to type 1 diabetes, but hitherto no studies on whether beta cell dysfunction could precede insulitis and clinical onset of type 1 diabetes are available.
methodsWe used 40-day-old BioBreeding (BB) DRLyp/Lyp rats (a model of spontaneous autoimmune type 1 diabetes) and diabetes-resistant DRLyp/+ and DR+/+ littermates (controls) to investigate beta cell function in vivo, and insulin and glucagon secretion in vitro. Beta cell mass was assessed by optical projection tomography (OPT) and morphometry. Additionally, measurements of intra-islet blood flow were performed using microsphere injections. We also assessed immune cell infiltration, cytokine expression in islets (by immunohistochemistry and qPCR), as well as islet Glut2 expression and ATP/ADP ratio to determine effects on glucose uptake and metabolism in beta cells.
resultsDRLyp/Lyp rats were normoglycaemic and without traces of immune cell infiltrates. However, IVGTTs revealed a significant decrease in the acute insulin response to glucose compared with control rats (1685.3 ± 121.3 vs 633.3 ± 148.7; p < 0.0001). In agreement, insulin secretion was severely perturbed in isolated islets, and both first- and second-phase insulin release were lowered compared with control rats, while glucagon secretion was similar in both groups. Interestingly, after 5-7 days of culture of islets from DRLyp/Lyp rats in normal media, glucose-stimulated insulin secretion (GSIS) was improved; although, a significant decrease in GSIS was still evident compared with islets from control rats at this time (7393.9 ± 1593.7 vs 4416.8 ± 1230.5 pg islet CONCLUSIONS/
interpretationThe present study identifies a deterioration of beta cell function and mass, and intra-islet blood flow that precedes insulitis and diabetes development in animals prone to autoimmune type 1 diabetes. These underlying changes in islet function may be previously unrecognised factors of importance in type 1 diabetes development.
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