| Title |
Early deficits in insulin secretion, beta cell mass and islet blood perfusion precede onset of autoimmune type 1 diabetes in BioBreeding rats
|
|---|---|
| Published in |
Diabetologia, December 2017
|
| DOI | 10.1007/s00125-017-4512-z |
| Pubmed ID | |
| Authors |
Anya Medina, Saba Parween, Sara Ullsten, Neelanjan Vishnu, Yuk Ting Siu, My Quach, Hedvig Bennet, Alexander Balhuizen, Lina Åkesson, Nils Wierup, Per Ola Carlsson, Ulf Ahlgren, Åke Lernmark, Malin Fex |
| Abstract |
Genetic 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. We 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. DRLyp/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-1 h-1; p < 0.0001). Compared with controls, OPT of whole pancreas from DRLyp/Lyp rats revealed significant reductions in medium (4.1 × 109 ± 9.5 × 107 vs 3.8 × 109 ± 5.8 × 107 μm3; p = 0.044) and small sized islets (1.6 × 109 ± 5.1 × 107 vs 1.4 × 109 ± 4.5 × 107 μm3; p = 0.035). Finally, we found lower intra-islet blood perfusion in vivo (113.1 ± 16.8 vs 76.9 ± 11.8 μl min-1 [g pancreas]-1; p = 0.023) and alterations in the beta cell ATP/ADP ratio in DRLyp/Lyp rats vs control rats. The 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. |
X Demographics
The data shown below were collected from the profiles of 10 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 30% |
| India | 1 | 10% |
| Germany | 1 | 10% |
| France | 1 | 10% |
| Spain | 1 | 10% |
| United Kingdom | 1 | 10% |
| Unknown | 2 | 20% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 6 | 60% |
| Scientists | 2 | 20% |
| Practitioners (doctors, other healthcare professionals) | 2 | 20% |
Mendeley readers
The data shown below were compiled from readership statistics for 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 12 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 3 | 25% |
| Student > Master | 2 | 17% |
| Researcher | 2 | 17% |
| Professor | 1 | 8% |
| Unknown | 4 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 25% |
| Immunology and Microbiology | 2 | 17% |
| Computer Science | 1 | 8% |
| Medicine and Dentistry | 1 | 8% |
| Unknown | 5 | 42% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 March 2018.
All research outputs
#4,620,016
of 23,009,818 outputs
Outputs from Diabetologia
#1,983
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Outputs of similar age
#99,423
of 439,982 outputs
Outputs of similar age from Diabetologia
#56
of 70 outputs
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