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Early deficits in i...
Early deficits in insulin secretion, beta cell mass and islet blood perfusion precede onset of autoimmune type 1 diabetes in BioBreeding rats
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- Medina, Anya (författare)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups,Skåne University Hospital
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- Parween, Saba (författare)
- Umeå University,Umeå universitet,Umeå centrum för molekylär medicin (UCMM),Umea Univ, Umea Ctr Mol Med, Umea, Sweden.
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- Ullsten, Sara (författare)
- Uppsala University,Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Vishnu, Neelanjan (författare)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups,Skåne University Hospital
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- Siu, Yuk Ting (författare)
- Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden.,Lund University
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- Quach, My (författare)
- Uppsala University,Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Bennet, Hedvig (författare)
- Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden.,Lund University
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- Balhuizen, Alexander (författare)
- Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden.,Lund University
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- Åkesson, Lina (författare)
- Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden.,Lund University,Skåne University Hospital
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- Wierup, Nils (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine,Skåne University Hospital
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- Carlsson, Per-Ola (författare)
- Uppsala University,Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Ahlgren, Ulf (författare)
- Umeå University,Umeå universitet,Umeå centrum för molekylär medicin (UCMM),Umea Univ, Umea Ctr Mol Med, Umea, Sweden.
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- Lernmark, Åke (författare)
- Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden.,Lund University
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- Fex, Malin (författare)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- 2017-12-06
- 2018
- Engelska.
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 61:4, s. 896-905
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Aims/hypothesis: 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.Methods: 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.Results: 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 x 109 +/- 9.5 x 107 vs 3.8 x 109 +/- 5.8 x 107 μm3; p = 0.044) and small sized islets (1.6 x 109 +/- 5.1 x 107 vs 1.4 x 109 +/- 4.5 x 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.Conclusions/interpretation: 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Beta cell dysfunction
- Beta cell mass
- Insulin secretion
- Islet blood flow
- Type 1 diabetes
- Beta cell dysfunction
- Beta cell mass
- Insulin secretion
- Islet blood flow
- Type 1 diabetes
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Medina, Anya
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Parween, Saba
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Ullsten, Sara
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Vishnu, Neelanja ...
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Siu, Yuk Ting
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Quach, My
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Bennet, Hedvig
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Balhuizen, Alexa ...
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Åkesson, Lina
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Wierup, Nils
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Carlsson, Per-Ol ...
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Ahlgren, Ulf
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Lernmark, Åke
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Fex, Malin
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Diabetologia
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Umeå universitet
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