Upstream Mechanisms of Glycogen Synthase Activation by Insulin and Insulin-like Growth Factor-I

Yamamoto‐Honda, Ritsuko; Tobe, Kazuyuki; Kaburagi, Yasushi; Ueki, Kohjiro; Asai, S.; Yachi, Makoto; Shirouzu, Mikako; Yodoi, Junji; Akanuma, Yasuo; Yokoyama, Shigeyuki; Yazaki, Yoshio; Kadowaki, Takashi

doi:10.1074/jbc.270.6.2729

Cited by 101 publications

(61 citation statements)

References 48 publications

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“…Representative ®elds are shown. Magni®cation=2006 p70 S6K activity may not always be necessary for the physiological e ects of NDF, since several recent reports have shown p70 S6K to be dispensable for PI3-K-mediated suppression of apoptosis (Dudek et al, 1997;Kau mann-Zeh et al, 1997;Kulik et al, 1997;Yao and Cooper, 1996), glycogen synthesis (Welsh et al, 1994;Yamamoto-Honda et al, 1995), and gene expression (Sutherland et al, 1995). Both the STAT and PLCg pathways can be activated by TGF-a treatment in prostate lines.…”

Section: Discussionmentioning

confidence: 99%

ErbB kinases and NDF signaling in human prostate cancer cells

et al. 1997

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Section: Discussionmentioning

confidence: 99%

ErbB kinases and NDF signaling in human prostate cancer cells

et al. 1997

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“…This is of relevance as phosphorylation of PKB is closely associated with activation of the enzyme. PI 3-kinase inhibitors are also known to block insulin activation of glycogen synthase [13,14] and this may involve PKB as the PKB lies between PI 3-kinase and glycogen synthase kinase 3 [15]. Lack of suitable reagents has precluded our ability to study insulin's regulation of glycogen synthase kinase 3 activity in the limited amounts of tissue available in the current studies.…”

Section: Discussionmentioning

confidence: 99%

“…Understanding the molecular mechanisms by which insulin regulates glucose transport and glycogen storage in skeletal muscle is therefore of great importance. Insulin acutely stimulates phosphoinositide-3 (PI 3)-kinase and evidence suggests that PI 3-kinase activity is necessary [8][9][10] and sufficient [11,12] for insulin stimulation of glucose transport and also necessary for insulin activation of glycogen synthase [13,14]. Further, there is evidence to suggest that protein kinase B (PKB) is an element of the signalling cascade leading from PI 3-kinase to activation of glycogen synthase in cell culture models [15,16].…”

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confidence: 99%

Involvement of phosphoinositide 3-kinase in insulin stimulation of MAP-kinase and phosphorylation of protein kinase-B in human skeletal muscle: implications for glucose metabolism

et al. 1997

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Insulin binding to its cell surface receptor activates a range of intracellular signalling cascades that ultimately result in the regulation of a number of important metabolic events within the cell [1]. Of particular importance is insulin stimulation of glucose transport and stimulation of glycogen deposition in muscle as this accounts for the bulk of insulin stimulated glucose disposal from the blood [2,3]. Peripheral insulin resistance at the level of skeletal muscle plays an important role in the development of hyperinsulinaemia and hyperglycaemia associated with obesity [4] and non-insulin-dependent diabetes [5]. The consensus of opinion is that defects in insulin signalling lead to the reduced ability of insulin to stimulate glucose disposal into muscle in insulin resistant individuals [6,7]. Understanding the molecular mechanisms by which insulin regulates glucose transport and glycogen storage in skeletal muscle is therefore of great importance. Insulin acutely stimulates phosphoinositide-3 (PI 3)-kinase and evidence suggests that PI 3-kinase activity is necessary [8][9][10] and sufficient [11,12] for insulin stimulation of glucose transport and also necessary for insulin activation of glycogen synthase [13,14]. Further, there is evidence to suggest that protein kinase B (PKB) is an element of the signalling cascade leading from PI 3-kinase to activation of glycogen synthase in cell culture models [15,16]. Insulin's regulation of these pathways has not been investigated in intact human skeletal muscle. Diabetologia (1997) Summary Isolated skeletal muscle from healthy individuals was used to evaluate the role of phosphoinositide 3-kinase (PI 3-kinase) in insulin signalling pathways regulating mitogen activated protein kinase (MAP-kinase) and protein kinase-B and to investigate whether MAP-kinase was involved in signalling pathways regulating glucose metabolism. Insulin stimulated glycogen synthase activity ( ≈ 1.7 fold), increased 3-o-methylglucose transport into human skeletal muscle strips ( ≈ 2 fold) and stimulated phosphorylation of the p42 ERK-2 isoform of MAP-kinase. This phosphorylation of p42 ERK2 was not blocked by the PI 3-kinase inhibitors LY294002 and wortmannin although it was blocked by the MAPkinase kinase (MEK) inhibitor PD 98059. However, PD98059 (up to 20 m mol/l) did not block insulin activation of glycogen synthase or stimulation of 3-o-methylglucose transport. Wortmannin and LY294002 did block insulin stimulation of protein kinase-B (PKB) phosphorylation and stimulation of 3-o-methylglucose transport was inhibited by wortmannin (IC 50 ≈ 100 nmol/l). These results indicate that MAP-kinase is activated by insulin in human skeletal muscle by a PI 3-kinase independent pathway. Furthermore this activation is not necessary for insulin stimulation of glucose transport or activation of glycogen synthase in this tissue.

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“…Wortmannin and more recently LY 294002 have been used to indicate the importance of PI 3-kinase in insulin-stimulated glucose uptake in adipocytes (5,10,63). The effects of insulin on glycogen synthase (7,8) or glycogen synthase kinase-3 (9, 10) are also blocked by inhibiting PI 3-kinase activity with wortmannin. In hepatoma cells, wortmannin has also been effectively used to block the actions of insulin on gene 33 expression (17), yet in this same study, wortmannin was ineffective in altering the response of PEPCK mRNA to insulin.…”

Section: Discussionmentioning

confidence: 99%

“…One report demonstrates that PI 3-kinase in 3T3-L1 cells is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation (5), whereas another shows that PI 3-kinase, while functioning upstream of Ras and Raf, is necessary for mediating insulin stimulation of c-fos transcription (6). Other reports using the PI 3-kinase inhibitor wortmannin, have implicated the involvement of PI 3-kinase in insulin regulation of glycogen synthase (7,8), glycogen synthase kinase-3 (9, 10), Glut-4-mediated glucose transport (5,11), membrane ruffling (12), and PEPCK expression (13,14).…”

mentioning

confidence: 99%

Insulin Regulation of Glucose-6-phosphate Dehydrogenase Gene Expression Is Rapamycin-sensitive and Requires Phosphatidylinositol 3-Kinase

Wagle¹,

Jivraj²,

Garlock³

et al. 1998

Journal of Biological Chemistry

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Glucose-6-phosphate dehydrogenase (G6PDH) controls the flow of carbon through the pentose phosphate pathway and also produces NADPH needed for maintenance of reduced glutathione and reductive biosynthesis. Hepatic expression of G6PDH is known to respond to several dietary and hormonal factors, but the mechanism behind regulation of this expression has not been characterized. We show that insulin similarly induces expression of endogenous hepatic G6PDH and a reporter construct containing 935 base pairs of the G6PDH promoter linked to luciferase in transient transfection assays. Using well tested and structurally distinct inhibitors of Ras farnesylation, lovastatin and B581, and a specific inhibitor of mitogen-activated protein kinase kinase activation, PD 98059, we show that the Ras/Raf/ mitogen-activated protein kinase pathway is not utilized for the insulin-induced stimulation of G6PDH gene expression in primary rat hepatocytes. Similarly, using well characterized inhibitors of phosphatidylinositol 3-kinase, wortmannin and LY 294002, we show that PI 3-kinase activity is necessary for the induction of G6PDH expression by insulin. Rapamycin, an inhibitor of FRAP protein, which is involved in the activation of pp70 S6 kinase, blocks the insulin induction of G6PDH, suggesting that S6 kinase is also necessary for the insulin induction of G6PDH expression.

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Upstream Mechanisms of Glycogen Synthase Activation by Insulin and Insulin-like Growth Factor-I

Cited by 101 publications

References 48 publications

ErbB kinases and NDF signaling in human prostate cancer cells

ErbB kinases and NDF signaling in human prostate cancer cells

Involvement of phosphoinositide 3-kinase in insulin stimulation of MAP-kinase and phosphorylation of protein kinase-B in human skeletal muscle: implications for glucose metabolism

Insulin Regulation of Glucose-6-phosphate Dehydrogenase Gene Expression Is Rapamycin-sensitive and Requires Phosphatidylinositol 3-Kinase

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