Induction of Human non-beta-cell Reprogramming to Insulin Production (II)
Description: <p>The proposed research will be articulated around two main aims: i) Modulate the reprogramming of islet α-cells, and ii) Determine the contribution of islet non-β-cells and brown adipose tissue (BAT) to glucose metabolism in physiological and diabetic conditions. The first aim will have two parts: ia) Characterization of the β-cell gene repertoire poised for expression in adult mouse and human α-cells upon insulin deficit, and ib) Designing molecular cocktails fostering the conversion of human α-cells into insulin-producers. Aim 2 will also comprise two elements: iia) Understanding the mechanisms underlying an improved glucose homeostasis upon non-β-cell loss, and iib) The role of BAT in whole body glucose homeostasis after β-cell loss: crosstalk with the pancreatic islet.</p><p>Expected results and impact for the field. The knowledge generated by the proposed studies should allow us to reprogram human non-b-cells in the image of β–cells. We expect to design combinations of molecules with high capacity to foster the intrinsic human α-cell plasticity. The prospective is thus the potential for translation into regenerative therapies to replenish the lost insulin-producing cells in diabetes. In the future, it should be possible to develop therapies to stimulate regeneration by reprogramming islet non-b-cells into β-like-cells in situ, namely directly in the pancreas of diabetic patients. Given the natural innate islet cell plasticity, which we recently discovered, reconstitution of functional insulin- producing cells by modulating islet cell type interconversions might become the most efficient and successful method for β-cell regeneration in clinical settings. In addition, by defining the role of BAT in regulating whole-body glucose homeostasis in normal and hyperglycemic conditions, we should help opening new therapeutic avenues for diabetes centered in targeting BAT function.</p>
Amount: CHF 800,000
Funding type: research
Funder scheme: Project funding
Start date: 2024-06-01
End date: 2028-05-31
Investigator: Herrera, Pedro Luis
Institution: University of Geneva – GE
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 10000879
OpenAlex ID: G6289964533