In Vivo Drug Discovery for Small Molecules Treating Diabetes

In Vivo Drug Discovery for Small Molecules Treating Diabetes

Wednesday, August 10, 2022
9:00 AM - 10:00 AM

Presenters: Olov Andersson, PhD

Organization: Karolinska Institute, Solna, Sweden

Olov Andersson, PhD, is an associate professor in the department of cell and molecular biology at the Karolinska Institute. His group is bridging developmental biology and drug discovery using the zebrafish model to elucidate organogenesis and related mechanisms of disease.

Andersson and his group are currently focusing on pancreatic beta-cell regeneration. Increasing the number of insulin-producing beta-cells might prove a better treatment for diabetes, which is at present controlled, but not cured, by insulin injections.

Diabetes is characterized by elevated blood glucose levels, a consequence of insufficient insulin supply and/or insulin resistance. Despite mechanistic differences, both type 1 and late-stage type 2 diabetes feature depletion of beta-cells.

Experimental ablation of beta-cells by chemical treatment or partial pancreatectomy in zebrafish and rodents is followed by significant recovery of the beta-cell mass, indicating that the pancreas has the capacity to regenerate. This regenerative capacity could potentially be exploited therapeutically - if the underlying mechanisms were better understood.

Andersson and his group perform unbiased chemical-genetic screens in zebrafish to identify compounds, signals and cellular mechanisms that promote beta-cell regeneration. The zebrafish model is particularly good for studying pancreatic development in vivo. First, the simplicity of its organ structures (i.e., the zebrafish embryo has only one pancreatic islet during the first week of development) allows rapid analysis of cellular changes. Second, zebrafish embryos are amenable to efficient transgenesis and drug delivery.

By using a wide range of techniques, he and his group are investigating three different cellular mechanisms of beta-cell regeneration:

  • Induction of beta-cell neogenesis
  • Promotion of beta-cell proliferation
  • Generation of ectopic insulin-producing cells

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