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

Diabetes is often characterized by a failure of insulin production by pancreatic Beta-cells to properly regulate glucose homeostasis. Insulin resistance
can lead to ОІ-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 ОІ-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 ОІ-cells, reducing Gsk- 3b not only preserved ОІ-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 ОІ-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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