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- Eliasson, Lena, et al.
(författare)
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PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells
- 1996
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 271:5250, s. 813-815
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Tidskriftsartikel (refereegranskat)abstract
- Hypoglycemic sulfonylureas represent a group of clinically useful antidiabetic compounds that stimulate insulin secretion from pancreatic beta cells. The molecular mechanisms involved are not fully understood but are believed to involve inhibition of potassium channels sensitive to adenosine triphosphate (KATP channels) in the beta cell membrane, causing membrane depolarization, calcium influx, and activation of the secretory machinery. In addition to these effects, sulfonylureas also promoted exocytosis by direct interaction with the secretory machinery not involving closure of the plasma membrane KATP channels. This effect was dependent on protein kinase C (PKC) and was observed at therapeutic concentrations of sulfonylureas, which suggests that it contributes to their hypoglycemic action in diabetics.
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| 4. |
- Lindford, AJ, et al.
(författare)
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The Helsinki approach to face transplantation
- 2019
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Ingår i: Journal of plastic, reconstructive & aesthetic surgery : JPRAS. - : Elsevier BV. - 1878-0539 .- 1748-6815. ; 72:2, s. 173-180
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Mir-Coll, J, et al.
(författare)
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Human Islet Microtissues as an In Vitro and an In Vivo Model System for Diabetes
- 2021
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 22:4
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Tidskriftsartikel (refereegranskat)abstract
- Loss of pancreatic β-cell function is a critical event in the pathophysiology of type 2 diabetes. However, studies of its underlying mechanisms as well as the discovery of novel targets and therapies have been hindered due to limitations in available experimental models. In this study we exploited the stable viability and function of standardized human islet microtissues to develop a disease-relevant, scalable, and reproducible model of β-cell dysfunction by exposing them to long-term glucotoxicity and glucolipotoxicity. Moreover, by establishing a method for highly-efficient and homogeneous viral transduction, we were able to monitor the loss of functional β-cell mass in vivo by transplanting reporter human islet microtissues into the anterior chamber of the eye of immune-deficient mice exposed to a diabetogenic diet for 12 weeks. This newly developed in vitro model as well as the described in vivo methodology represent a new set of tools that will facilitate the study of β-cell failure in type 2 diabetes and would accelerate the discovery of novel therapeutic agents.
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| 6. |
- Rorsman, Patrik, et al.
(författare)
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Ion channels, electrical activity and insulin secretion
- 1994
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Ingår i: Diabete & metabolisme. - 0338-1684. ; 20:2, s. 138-145
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Tidskriftsartikel (refereegranskat)abstract
- The insulin-secreting pancreatic beta cell is electrically excitable and changes in the membrane potential play an important role in coupling the metabolism of glucose (and other nutrient secretagogues) to the discharge of the insulin-containing granule. The application of the patch-clamp technique, which permits the recordings of the minute currents associated with the opening of individual ion channels, to pancreatic islet cells has revolutionized our understanding of the beta cell electrophysiology. Here we review some of the recent progress in the field. The properties of functionally important ion channels are described and their possible roles are discussed.
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