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Islet cell exocytosis

Department of Clinical Sciences Malmö

Head: Professor Lena Eliasson

 

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Current members

Lena Eliasson, PI; Professor in Experimental Diabetes Research
Anna Wendt, Assistant Professor
Jonathan LS Esguerra, Associate Researcher
Elaine Cowan, Post-doc
Alexandros Karagiannopoulos, PhD student
Efraim Westholm, PhD student
Anna-Maria Veljanovska Ramsay, Lab technician
Eugenia Cordero, Lab technician

Associated members

Anna Edlund, PhD
Mototsugu Nagao, MD, Phd

Overall objective of our studies

Islet cell function is central in glucose homeostasis. Dysfunction leads to diabetes development. The main focus of our research is to understand islet cell function in the aetiology of type-2 diabetes (T2D), a complex disease dependent on both genetic background and life-style factors. The disease is associated with deregulated secretion from the α- and ß-cells within the pancreatic islet of Langerhans. In addition, we have an interest to understand islet cell function in more rare diabetes types, such as cystic fibrosis related diabetes (CFRD) and glucocorticoid induced diabetes.

The main focus of our research is to investigate the regulation of insulin and glucagon secretion from a cell physiological perspective and with a specific interest in how non-coding RNAs (ncRNA) are involved in this regulation, our group focuses mainly on long non-coing RNA (lncRNA) and microRNA (miRNA) and their roles in islet cell function. In recent years, we have discovered novel miRNAs involved in the post-transcriptional regulation of gene expression essential for insulin secretion in the ß-cell. MiRNAs have been shown to be differentially expressed in T2D, and we hypothesize that miRNAs are key in the adjustment of ß-cell function during the development of the disease. Failure to compensate for the increased demand on the ß-cell leads to full-blown diabetes. Although we today know much more about the role of miRNAs in ß-cell function there are still many open questions and the role of specific miRNAs in α-cell glucagon secretion is largely unknown. Moreover, basic knowledge around islet miRNAs needs to be transferred to use for predicition and treatment of the disease.

Hence, the overall objective of our current research is to investigate how non-coding RNAs impact the regulation of islet cell function and how this can be involved in the eatiology of T2D, CFRD and glucocorticoid induced diabetes.

 

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Selected recent publications

  1. Nagao M, Esguerra JLS, Asai A, Ofori JK, Edlund A, Wendt A, Sugihara H, Wollheim CB, Oikawa S, Eliasson L. Potential Protection Against Type 2 Diabetes in Obesity Through Lower CD36 Expression and Improved Exocytosis in β-Cells. Diabetes. 2020 Jun;69(6):1193-1205. doi: 10.2337/db19-0944.
  2. Eliasson L and Esguerra JLS. MicroRNA Networks in Pancreatic Islet Cells: Normal Function and Type 2 Diabetes. Diabetes. 2020 May;69(5):804-812. doi: 10.2337/dbi19-0016.
  3. Wendt A and Eliasson L. Pancreatic α-cells - The unsung heroes in islet function. Semin Cell Dev Biol. 2020 Jan 23. pii: S1084-9521(19)30078-3. doi: 10.1016/j.semcdb.2020.01.006.
  4. Esguerra JLS, Ofori JK, Nagao M, Shuto Y, Karagiannopoulos A, Fadista J, Sugihara H, Groop L and Eliasson L, Glucocorticoid induces human beta cell dysfunction and involves the riborepressor GAS5 lincRNA, Mol Metab, December 2019, DOI: 10.1016/j.molmet.2019.12.012
  5. Bijkerk R, Esguerra JLS, Ellenbroek JH, Au YW, Hanegraaf MAJ, de Koning EJ, Eliasson L#* and van Zonneveld AJ#. In Vivo Silencing of MicroRNA-132 Reduces Blood Glucose and Improves Insulin Secretion. Nucleic Acid Ther. 2019 Apr;29(2):67-72. doi: 10.1089/nat.2018.0763.
  6. Edlund A, Barghouth M, Huhn M, Abels M, Esguerra J, Mollet I, Svedin E, Wendt A, Renstrom E, Zhang E, Wierup N, Scholte BJ, Flodström-Tullberg M and Eliasson L. Defective exocytosis and processing of insulin in a cystic fibrosis mouse model. J Endocrinol. 2019 Feb 1. pii: JOE-18-0570.R1. doi: 10.1530/JOE-18-0570.