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GSK-3β function in bone regulates skeletal development, whole-body metabolism, and male life span.

Endocrinology | 2013

Glycogen synthase kinase 3 β (GSK-3β) is an essential negative regulator or "brake" on many anabolic-signaling pathways including Wnt and insulin. Global deletion of GSK-3β results in perinatal lethality and various skeletal defects. The goal of our research was to determine GSK-3β cell-autonomous effects and postnatal roles in the skeleton. We used the 3.6-kb Col1a1 promoter to inactivate the Gsk3b gene (Col1a1-Gsk3b knockout) in skeletal cells. Mutant mice exhibit decreased body fat and postnatal bone growth, as well as delayed development of several skeletal elements. Surprisingly, the mutant mice display decreased circulating glucose and insulin levels despite normal expression of GSK-3β in metabolic tissues. We showed that these effects are due to an increase in global insulin sensitivity. Most of the male mutant mice died after weaning. Prior to death, blood glucose changed from low to high, suggesting a possible switch from insulin sensitivity to resistance. These male mice die with extremely large bladders that are preceded by damage to the urogenital tract, defects that are also seen type 2 diabetes. Our data suggest that skeletal-specific deletion of GSK-3β affects global metabolism and sensitizes male mice to developing type 2 diabetes.

Pubmed ID: 23904355 RIS Download

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p57 (H-91) (antibody)

RRID:AB_2078155

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GSK-3-alpha Antibody (antibody)

RRID:AB_2114897

This polyclonal targets Gsk3a

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PCNA (PC10) Mouse mAb (antibody)

RRID:AB_2160343

This monoclonal targets PCNA

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Cleaved Caspase-3 (Asp175) Antibody (antibody)

RRID:AB_2341188

This polyclonal targets Cleaved Caspase-3 (Asp175)

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β-Catenin Antibody (antibody)

RRID:AB_331149

This polyclonal targets β-Catenin

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Phospho-GSK-3 (Ser9) Antibody (antibody)

RRID:AB_331405

This polyclonal targets Phospho-GSK-3 (Ser9)

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Anti-β-Actin Antibody (antibody)

RRID:AB_476744

This monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH

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GSK-3beta (27C10) Rabbit mAb (antibody)

RRID:AB_490890

This monoclonal targets GSK-3beta (27C10) Rabbit mAb

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