How does insulin stimulate glycogen synthesis?

Insulin (100 nM) caused a maximum 110% increase in glycogen synthase activity in 5 min.

Glycogen; Insulin; Metabolic Pathway; Metabolism; Rating and Stats

Bai G, Zhang ZJ, Werner R, Nuttall FQ, TanAW and Lee EY: The primary structure of rat liver glycogen synthasededuced by cDNA cloning. Absence of phosphorylation sites 1a and1b. J Biol Chem. 265:7843–7848. 1990.

59. Bijur GN, Jope RS. Glycogen synthase kinase-3 beta is highly activated in nuclei and mitochondria.  2003;14:2415-9

Insulin promotes glycogen synthesis in the absence of …

84. Palomo V, Perez DI, Perez C, Morales-Garcia JA, Soteras I, Alonso-Gil S. . 5-imino-1,2,4-thiadiazoles: first small molecules as substrate competitive inhibitors of glycogen synthase kinase 3. 2012;55:1645-61

21. Grimes CA, Jope RS. The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling.  2001;65:391-26

Fang X, Yu SX, Lu Y, Bast RC Jr, WoodgettJR and Mills GB: Phosphorylation and inactivation of glycogensynthase kinase 3 by protein kinase A. Proc Natl Acad Sci USA.97:11960–11965. 2000. : :


Glycogen Synthase Kinase-3 (GSK-3)-Targeted Therapy …

Chari-Bitron A, Lepkovsky S, Lemmon RM andDimick MK: Conversion of glucose to glycogen after ingestion of ahigh-carbohydrate diet. Am J Physiol. 198:787–792. 1960.

Glycogen Biosynthesis; Glycogen Breakdown - Oregon …

Gebhardt et al.[] showed application of emodin (82) and its ethylenediamine analog 83 as non-ATP competitive inhibitors of GSK-3 (Table ). Addition of the ethylenediamine group on the emodin nucleus increased potency of inhibition (IC50 0.56±0.02 µM, 83), reduced cytotoxicity and generated an insulin sensitizing effect mediated by increasing hepatocellular glycogen and fatty acid biosynthesis. Selectivity's of compounds 82 and 83 were evaluated against twelve protein kinases including eleven of human protein kinases. Compound 83 showed high selectivity towards GSK-3β but 82 failed to do so.

How does insulin stimulate glycogen synthesis? - …

GSK-3 is involved in a large number of key cellular processes and exhibits dysregulation in a wide variety of disease states. Accordingly, modulation of GSK-3 activity has been deemed an important approach for therapy and imaging. As shown in this limited review, a very large number of GSK-3 inhibitors have been synthesized. However, as reflected in the slow progress of these inhibitors toward clinical translation, a number of challenges remain. Adverse effects caused by off-target activity of GSK-3 inhibitors were determined after the screening of compounds that bind to the ATP-competitive binding site conserved across a broad range of kinases. Therefore, it would be extremely advantageous to design and develop GSK-3 inhibitors that can selectively target individual pathways and differentiate between the phosphorylated and non-phosphorylated forms of GSK-3. In this regard, parallel development of a therapeutic molecule with a closely related imaging biomarker may allow early evaluation of drug candidates based on noninvasive imaging measurements of the target-to-background ratios. Imaging can also be instrumental in defining the brain uptake patterns of GSK inhibitors intended for brain-related disorders, which would allow for the early dismissal of candidates that show poor brain penetration or retention. Alternative approaches to ligand design may be needed to improve GSK-3 targeting specificity for both therapy and imaging purposes.

Glycogen Metabolism and Synthesis MASTER - Quizlet

As small non-coding RNAs, miRNAs play a pivotal rolein post-transcriptional regulation. miRNAs can bind to and promotethe deadenylation and degradation of target mRNAs (,). Translational repression is anotherimportant function of miRNAs. It can directly bind to the 3′-UTR oftarget mRNAs and inhibit the translational initiation (). Studies have demonstrated thatmiRNAs are involved in the regulation of multiple insulinresistance-induced diseases (). In T2D, miR-144 has been shown to promote insulinresistance by directly targeting mRNA (). The suppression of IRS1 mediated bymiR-126 has also been shown to result in mitochondrial dysfunctionand insulin resistance (). Thesitmulation of Akt activation by insulin is critical forglycometabolism, and the obesity-induced miR-143 overexpression hasbeen shown to lead to hyperglycemia by inactivating the Aktsignaling pathway (). A studyusing let-7 family transgenic mice demonstrated that let-7overexpression may contribute to the development of T2D (). Protein tyrosine phosphatase 1B(PTP1B) impairs the insulin signaling pathway through thedephosphorylation of IR at tyrosine residues. The 3′-UTR of mRNA is the target of miR-122, and decreased miR-122expression has been shown to result in hepatic insulin resistance(). In mouse models ofobesity, miR-103/107 is upregulated. The blockage of miR-103/107has been shown to promote insulin sensitivity by elevatingcaveolin-1-mediated IR activation (). Phosphatase and tensin homologdeleted on chromosome 10 (PTEN), the direct target of miR-21(), is the key phosphotase ofAkt which can negatively regulate the Akt signaling pathway. Ininsulin-resistant adipocytes, the suppressed expression of miR-21and impaired Akt signaling pathway has been observed (). The transport of glucose is alsoregulated by miRNAs, and the transmembrane protein GLUTs play anessential role in glucose transport. Elevated miR-133 levels havebeen shown to reduce the insulin-stimulated glucose uptake bydownregulating GLUT4 expression (). In cardiomyocytes, miR-223 has beenshown to promote GLUT4 expression and increase glucose uptake(). Insulin resistance is theintrinsic complication of polycystic ovary syndrome (PCOS), andoverexpressed miR-93 in patients with PCOS binds to the 3′-UTR of mRNA and reduces its protein translation (). Microarray analysis has furtherindicated that the expression of several miRNAs is alteredfollowing burn injury. In comparison with normal skin tissue, atotal of 32 upregluated and 34 downregulated miRNAs were identifiedin the skin tissue of patients who sustained burn injuries(). The expression levels ofmiR-144 in the skin tissue of the burned patients, which candirectly target the 3′-UTR of mRNA (), were 16-fold higher than those innormal skin tissue (). Thissuggests that miRNAs, such as miR-144, play an essential role inpromoting burn-induced insulin resistance by suppressing theactivation of the IR/IRS signaling pathway.