Genetic Deficiency Of Glycogen Synthase Kinase-3Beta Corrects Diabetes In Mouse Models Of Insulin Resistance

February 20, 2008 – 6:55 am | posted in Diabetes

Diabetes is often characterized by a failure of insulin production by pancreatic Beta-cells to properly regulate glucose homeostasis. Insulin resistance can lead to ?-cell failure, and our studies have focused on elucidating the mechanisms involved in this postnatal failure.

This week in the open-access journal PLoS Biology, Katsuya Tanabe, James Woodgett, and M. Alan Permutt have evaluated a new negatively regulated enzyme of the insulin signaling pathway, Glycogen synthase kinase 3 (Gsk-3)) specifically within insulin producing pancreatic ?-cells. When this enzyme is elevated, it can impair replication and increase cell death, resulting in loss of insulin producing cells and diabetes. Gsk-3 is also known to regulate cell death and proliferation in neurons.

They assessed the role of Gsk-3 on glucose homeostasis in two different mouse models of Insulin resistance. They also demonstrated that genetically reducing the levels of Gsk-3b in the insulin resistant mouse improved glucose homeostasis.

In another model where severe insulin resistance is associated with destruction of ?-cells, reducing Gsk- 3b not only preserved ?-cells by increasing proliferation and reducing cell death it also corrected diabetes.

Controlling activity of Gsk-3 could lead to new hopes for maintaining or improving ?-cell number and prevention of diabetes.

Genetic deficiency of glycogen synthase kinase-3b corrects diabetes in mouse models of insulin resistanceTanabe K, Liu Z, Patel S, Doble BW, Li L, et al.
PLoS Biol 6(2): e37. doi:10.1371/journal.pbio.0060037
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