Insulin And Gsk3

In 1960 Joseph Larner reported that the activity of glycogen synthase was increased within minutes when rat diaphragms were incubated with insulin 11 and, a few years later, he showed that this resulted from decreased phos-phorylation of this enzyme 12 . Following the discovery that PKA can phos-phorylate and inhibit GSK-3 in vitro 13,14 , it was thought that insulin must exert its effect on glycogen synthase by inhibiting PKA, but no decrease in the concentration of cyclic AMP could be...

Therapeutic Applications Lithium Or Other Inhibitors Of Gsk3

Looming above all of the individual actions of GSK-3 and the effects of its inhibition by lithium and other drugs is the ultimate outcome goal Is it possible for inhibition of GSK-3 to provide therapeutic relief from human disease Lithium has passed this test, as it is unquestionably effective in the treatment of bipolar mood disorder. Although the therapeutic mechanism of action of lithium in bipolar mood disorder is not known, it is evident that many effects of GSK-3, and thus of lithium, can...

Role Of Gsk3 In Neuronal Morphogenesis

Different approaches have been adopted in order to define the precise role of GSK-3 in neurons. Unfortunately, mutant mice lacking GSK-3P have proved to be uninformative, since disruption of the murine GSK-3 beta gene provokes embryonic lethality due to severe liver degeneration at midgesta-tion 14 . Nevertheless, the recent analysis of hippocampal neurons in cell culture has provided evidence for a novel role for GSK-3 in axon specification. Figure 3.2 Some pathways that modulate the kinase...

References

The hormonal control of glycogen metabolism in mammalian muscle by multivalent phosphorylation. Biochem. Soc. Trans., 7, 459-80. 2. Embi N., Rylatt D.B., Cohen P. (1980). Glycogen synthase kinase-3 from rabbit skeletal muscle Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur. J. Biochem., 107, 519-527. 3. Woodgett J.R. (1991). cDNA cloning and properties of glycogen synthase kinase-3. Methods Enzymol., 200, 564-577. 4. Plyte S.E., Hughes K.,...

Gsk3 Regulation And Alzheimers Disease

Since its discovery, GSK-3 has been found to be involved in many physiological process. GSK-3 plays important roles in embryonic development, cell differentiation, microtubule dynamics, cell cycle division, cell adhesion, glucose metabolism, and apoptosis 19,20 . In addition, a growing amount of experimental data has demonstrated its involvement in some pathological processes as Alzheimer's disease. The GSK-3 protein (E.C. 2.7.1.37) is a proline-directed serine threonine protein kinase that was...

Cns Disorders And Gsk3 Inhibitor Lithium

In FTDP linked to chromosome 17, the presence of some mutations in Tau correlates with the onset of the disease. In this case, it has been found that those mutations could affect to the dephosphorylation of Tau molecule which is already pre-phosphorylated 31 , and this pre-phosphorylation could be due to GSK-3 32 . Tau mutations that result in Frontotemporal dementia (FTD) consist of NFT pathology. Transgenic mouse models with these mutations (P301L, V337M, R406W) also exhibit NFT like...

Introduction To Mood Disorders And Limitations Of Current Treatments

Bipolar disorder and unipolar depression are classified as mood disorders. They are common, severe, and chronic illnesses. Depression is typified by a depressed mood, anhedonia (inability to experience pleasure), feelings of worthlessness or excessive guilt, impaired sleep (either insomnia or hyper-somnia), cognitive and concentration deficits, psychomotor changes, recurrent thoughts of death or suicide, and a variety of neurovegetative symptoms. In bipolar disorder, patients typically...

Pathways Controlling Gsk3 Activity In Neurons

Since many different pathways have been described in which GSK-3 plays an important or essential role, we will only summarize some of these here. Historically GSK-3 fulfills a significant role in the Insulin IGF1 and Wnt Shaggy signaling pathways. However, more recently it has become clear that GSK-3 is present in many other pathways such as those involving NGF, Estradiol, or Reelin. Moreover it seems likely that there will be many more in which the relative importance of GSK-3 remains to be...

Gsk3 And Insulin Resistance

GSK-3, one of the final regulatory proteins in glycogen production, is an attractive target for non-insulin-dependent diabetes mellitus (NIDDM). In NIDDM biopsy tissue GSK-3 activity is inversely correlated to glycogen synthase activity implicating GSK-3 as contributing to insulin resistance 27,28 . Insulin and insulin receptors are expressed in the brain, including the medial temporal regions that support the formation of memory 29 . Some NIDDM patients are also afflicted with verbal and...