Research areas and keywords
UKÄ subject classification
- Cell and Molecular Biology
- Endocrinology and Diabetes
- insulin secretion, glucagon secretion, exocytosis, ion channels, microRNA, non-coding RNA, Type 2 diabetes, Islet of Langerhans, beta cell, alpha cell, CFTR, CFRD
The overall goal of my research has always been to increase the knowledge regarding alpha- and beta-cell function for the possible development of better treatment for patients with diabetes. Type 2 diabetes (T2D) is the major form of diabetes and obesity and physical inactivity influence the disease development leading to the elevated blood glucose level. The main hormone regulating the blood glucose levels is insulin, secreted from beta cells, and glucagon, secreted from alpha cells. Both cell-types situated within the Islet of Langerhans in the pancreas. My research focus is to understand how we can circumvent the reduced capacity of the pancreatic beta cells to secrete enough insulin, and why the control of alpha cell glucagon secretion becomes disturbed in diabetes.
In my early scientific years, I learned the patch-clamp technique and used capacitance measurements to study exocytosis. During this period we could reveal how the influx of Ca2+ regulates exocytosis and how second messengers like ATP and cAMP are important for priming of the insulin granules to become release ready. Priming is an important step in the release of insulin from the beta cell (and the alpha cell). Others and we suggest that the beta cell release primed insulin granules during first phase insulin secretion, which is lacking in individuals with pre-diabetes. I still have a research focus on the priming process mapping different components involved.
MicroRNAs (miRNAs) are small non-coding RNAs responsible for posttranscriptional regulation of gene expression. I was involved in the first study published in 2004 describing an islet specific miRNA, miR-375. We showed that this miRNA had effects on exocytosis when overexpressed. Today we know that miR-375 also regulate several other mechanisms. Since then my research group have performed detailed analysis of miRNAs in beta-cell function by investigations of islets from different diabetes animal models, and from human donors. We are currently performing functional investigations of key miRNAs and their role in insulin- and/or glucagon secretion. In the future, we will use this knowledge in the attempt to rescue the diabetic phenotype using LNA antagomirs as possible therapeutics to influence insulin and glucagon secretion.
In my goal to understand beta- and alpha-cell regulation, we have lately demonstrated the novel finding that the chloride channel CFTR is present in both mouse and human beta- and alpha-cells. In beta-cells, CFTR act as a regulator of the Ca2+ activated chloride channel ANO1 to regulate granular priming and exocytosis of insulin granules. In alpha-cells, CFTR is important for regulation of alpha-cell electrical activity and the generation of action potentials. This is of interest since patients with cystic fibrosis (CF) today often develop CF-related Diabetes (CFRD).
I am part of Lund University Diabetes Centre (LUDC) formed through a Swedish Research council Linneus grant more than 10 years ago. This has made it possible for me to collaborate with colleagues and to perform functional follow-ups of both epigenetic and genetic observations from humans. Through the centre, we have access to human islets from which we have investigated the miRNA-profile and together we perform large-scale RNA-sequencing studies in human islets that has given us the opportunity to investigate other non-coding RNAs such as the lncRNAs and their role in beta cell function. We have access to well-designed patient cohort materials in which we investigate miRNAs as potential blood based biomarkers of T2D and its complications.
Altogether, our studies aim to increase the understanding of insulin- and glucagon secretion in the complex disease diabetes.
Recent research outputs
Research output: Contribution to journal › Article