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- Dekki, N, et al.
(författare)
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Type 1 diabetic serum interferes with pancreatic beta-cell Ca2+-handling
- 2007
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Ingår i: Bioscience reports. - : Portland Press Ltd.. - 0144-8463 .- 1573-4935. ; 27:6, s. 321-326
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to clarify the frequency of patients with type 1 diabetes that have serum that increases pancreatic β-cell cytoplasmic free Ca2+ concentration, [Ca2+]i, and if such an effect is also present in serum from first-degree relatives. We also studied a possible link between the serum effect and ethnic background as well as presence of autoantibodies. Sera obtained from three different countries were investigated as follows: 82 Swedish Caucasians with newly diagnosed type 1 diabetes, 56 Americans with different duration of type 1 diabetes, 117 American first-degree relatives of type 1 diabetic patients with a mixed ethnic background and 31 Caucasian Finnish children with newly diagnosed type 1 diabetes. Changes in [Ca2+]i, upon depolarization, were measured in β-cells incubated overnight with sera from type 1 diabetic patients, first-degree relatives or healthy controls. Our data show that there is a group constituting approximately 30% of type 1 diabetic patients of different gender, age, ethnic background and duration of the disease, as well as first-degree relatives of type 1 diabetic patients, that have sera that interfere with pancreatic β-cell Ca2+-handling. This effect on β-cell [Ca2+]i could not be correlated to the presence of autoantibodies. In a defined subgroup of patients with type 1 diabetes and first-degree relatives a defect Ca2+-handling may aggravate development of β-cell destruction.
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- Miettinen, PJ, et al.
(författare)
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Downregulation of EGF receptor signaling in pancreatic islets causes diabetes due to impaired postnatal beta-cell growth
- 2006
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:12, s. 3299-3308
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Tidskriftsartikel (refereegranskat)abstract
- Epidermal growth factor receptor (EGF-R) signaling is essential for proper fetal development and growth of pancreatic islets, and there is also evidence for its involvement in β-cell signal transduction in the adult. To study the functional roles of EGF-R in β-cell physiology in postnatal life, we have generated transgenic mice that carry a mutated EGF-R under the pancreatic duodenal homeobox-1 promoter (E1-DN mice). The transgene was expressed in islet β- and δ-cells but not in α-cells, as expected, and it resulted in an ∼40% reduction in pancreatic EGF-R, extracellular signal–related kinase, and Akt phosphorylation. Homozygous E1-DN mice were overtly diabetic after the age of 2 weeks. The hyperglycemia was more pronounced in male than in female mice. The relative β-cell surface area of E1-DN mice was highly reduced at the age of 2 months, while α-cell surface area was not changed. This defect was essentially postnatal, since the differences in β-cell area of newborn mice were much smaller. An apparent explanation for this is impaired postnatal β-cell proliferation; the normal surge of β-cell proliferation during 2 weeks after birth was totally abolished in the transgenic mice. Heterozygous E1-DN mice were glucose intolerant in intraperitoneal glucose tests. This was associated with a reduced insulin response. However, downregulation of EGF-R signaling had no influence on the insulinotropic effect of glucagon-like peptide-1 analog exendin-4. In summary, our results show that even a modest attenuation of EGF-R signaling leads to a severe defect in postnatal growth of the β-cells, which leads to the development of diabetes.
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- Catrina, SB, et al.
(författare)
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Breathless after separation... from tumour
- 2008
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 32:5, s. 1420-1421
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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