Severe insulin-deficient diabetes – mechanisms & pathways
Leaders for work package 4: Lena Eliasson and Enming Zhang (Enming Zhang acts as Erik Renström’s deputy)
The severe insulin-deficient diabetes (SIDD) subgroup is characterised by non-autoimmune impaired insulin secretion and was previously hidden in the type 2 diabetes group. In this work package we aim to examine underlying mechanisms of to find possible pharmacological targets to be used in personalised treatment.
LUDC-ICR has access to some of the largest repositories of well-characterised human islets from patients with and without diabetes in the world, allowing us to test most hypotheses involving pancreatic islet function. This work package utilises our large islet RNA data sets as well as a new human islet cell encyclopedia generated by single-cell RNA sequencing, and focuses on miRNA translation pathways, membrane receptor and intracellular Ca2+ signalling pathways.
Objectives
- Identify targetable mechanisms and pathways underlying initiation and progression of SIDD.
- Identify disease heterogeneities that influence the insulin secretion process.
- Evaluate the therapeutic potential of novel insulinotropic and glucagonostatic agents.
Selected publications
- Title: A critical role of the mechanosensor PIEZO1 in glucose-induced insulin secretion in pancreatic β-cells
Reference: Nature Communications, 13, 4237, (2022) - Title: Human Islet MicroRNA-200c Is Elevated in Type 2 Diabetes and Targets the Transcription Factor ETV5 to Reduce Insulin Secretion
Reference: Diabetes, 71 (2), 275-284 (2022) - Title: The MafA-target gene PPP1R1A regulates GLP1R-mediated amplification of glucose-stimulated insulin secretion in β-cells
Reference: Metabolism Clinical and Experimental, 118, 154734 (2021) - Title: Overexpressed beta cell CART increases insulin secretion in mouse models of insulin resistance and diabetes
Reference: Peptides, 151, 170747 (2022) - Title: Glucocorticoid induces human beta cell dysfunction by involving riborepressor GAS5 LincRNA
Reference: Molecular Metabolism, 32, 160-167 (2020)
Contact
Lena Eliasson
Work Package Leader
Professor of experimental diabetes research
+46 (0)70 522 54 14
+46 (0)40 39 11 53
lena [dot] eliasson [at] med [dot] lu [dot] se (lena[dot]eliasson[at]med[dot]lu[dot]se)
Enming Zhang
Work Package Leader
Associate Professor of experimental endocrinology
+46 (0)76 036 44 87
+46 (0)40 39 11 18
enming [dot] zhang [at] med [dot] lu [dot] se