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Islet cell exocytosis

Department of Clinical Sciences Malmö
Head: Professor Lena Eliasson

Islet cell exocytosis
Autumn 2015

Group members

Jones Ofori, PhD student

Anna Edlund, PhD student
Mototsugu Nagao, Postdoc Fellow
Anna Wendt, Associate Researcher
Jonathan LS Esguerra, Associate Researcher
Anna-Maria Veljanovska Ramsay, Lab technician
Britt-Marie S Nilsson, Lab technician

Former members

Helena Malm, PhD student
Vishal A. Salunkhe, PhD student

Inês G. Mollet, Associate Researcher
Sofia A Andersson, PhD
Morten Gram Pedersen, Post-doc

Yang de Marinis, PhD
Jenny Vikman, PhD

Introduction

Type-2 diabetes (T2D) is a complex disease dependent on both genetic background and life-style factors. The disease is associated with increase in blood glucose level which is due to reduced insulin secretion from the pancreatic β-cell and impaired insulin action at the target cells.  Diabetes is also associated with a perturbed glucagon secretion. 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.  Belonging to the group of ncRNAs are microRNAs (miRNA). The function of miRNAs is to suppress the expression of genes by mRNA degradation, mRNA deadenylation and/or translational repression.

The overall objective of overall objective of our research is to investigate how T2D associated environmental factors effects the islet hormone secretion with a specific focus on islet non-coding RNAs and their involvement in etiology of the disease.  We will specifically focus on the following specific projects

1. Mechanisms behind impaired insulin secretion and exocytosis in type 2 diabetes – involvement of non-coding RNAs

a. Global expression profiling of non-coding RNAs in islets from non-diabetic and T2D donors.

b. Perform detailed cellular analysis of pathways involved in miRNA-controlled regulation of insulin secretion and exocytosis.

c. Rescue of impaired insulin secretion and hyperglycemia using LNA antagomirs

d. Identify blood-based miRNAs that can be used as biomarkers of T2D.

2. CFTR in pancreatic islet cells – role in the development of Cystic fibrosis-related diabetes (CFRD)?

3. Control of glucagon secretion and exocytosis involving alpha- cell enriched microRNAs (in collaboration with Morten Gram Pedersen, Padua University, Italy)  

4. Influence of microRNAs in the functional adjustments of secretion and exocytosis in pancreatic islets cells during obesity-induced development of Type 2 diabetes (T2D) - A study on mouse lines with different susceptibilities (resistant [SDG-R] and prone [SDG-P]) to HFD-induced glucose intolerance. (In collaboration with Prof. Shinichi Oikawa and Prof. Hitoshi Sugihara of Nippon Medical School.)

5. Statins – good or bad from a diabetogenic perspective?

6. Role of OPN in islet cells - A study of the OPN-/- mice.

Impact

Ultimately, our research gives new insight into treatment and discovery strategies of T2D, and we anticipate our novel findings will be essential for future prediction, prevention and treatment of T2D.

 

 The exocytotic process

 

Award:

LUDC/DPLU award to PhD-student 2016:  Anna Edlund, PhD-student working on the role of CFTR in pancreatic alpha- and beta-cells.

Highlights:

  1. Salunkhe VA, Mollet IG, Ofori JK, Malm HA, Esguerra JLS, Reinbothe T, Stenkula KG, Wendt A, Eliasson L, Vikman J. Dual Effect of Rosuvastatin on Glucose Homeostasis Through Improved Insulin Sensitivity and Reduced Insulin secretion 2016, EBioMedicine Aug;10:185-94. doi: 10.1016/j.ebiom.2016.07.007.
  2. Mollet IG, Malm HA, Wendt A, Orho-Melander M, Eliasson L Integrator of Stress Responses Calmodulin Binding Transcription Activator 1 (Camta1) Regulates miR-212/miR-132 Expression and Insulin Secretion. J Biol Chem. 2016 Aug 26;291(35):18440-52. doi: 10.1074/jbc.M116.716860.
  3. Edlund A, Esguerra JLS, Wendt A, Flodström-Tullberg, M and Eliasson L*,  CFTR and Anocatamin 1 (ANO1) contribute to cAMP amplified exocytosis and insulin secretion in human and murine pancreatic β-cells, BMC Medicine, 2014, 12:87 doi:10.1186/1741-7015-12-87
  4. Eliasson L and Esguerra JL. Role of non-coding RNAs in pancreatic beta-cell development and physiology. Acta Physiol (Oxf). 2014 Jun;211(2):273-84.

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00