Regulation of GLUT4 protein and glycogen synthase during muscle glycogen synthesis after exercise

Ivy, John L.; Kuo, Chia‐Hua

doi:10.1046/j.1365-201x.1998.0302e.x

Cited by 105 publications

(87 citation statements)

References 46 publications

(72 reference statements)

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“…GLUT4 translocation and expression levels are correlated with whole-body insulin-mediated glucose homeostasis [41,42]. More and more attention has been drawn to the link between IR and GLUT4, and some interesting conclusions have been made [43].…”

Section: Discussionmentioning

confidence: 99%

Anti-diabetic activity of stigmasterol from soybean oil by targeting the GLUT4 glucose transporter

Wang

Yang

et al. 2017

Food & Nutrition Research

100

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The present study investigated the anti-diabetic activity and potential mechanism of stigmasterol (SMR), which is a kind of phytosterols derived from the edible soybean oil in vitro and in vivo. SMR displayed a mild GLUT4 translocation activity by 1.44-fold in L6 cells. L6 cells were treated with different concentration of SMR, showing significant effects on the enhancing glucose uptake. SMR administrated orally to the KK-Ay mice significantly alleviated their insulin resistance and oral glucose tolerance with reducing fasting blood-glucose levels and blood lipid indexes such as triglyceride and cholesterol. Moreover, the GLUT4 expression in L6 cells, skeletal muscle and white adipose tissue had been also enhanced. In this paper we conclude that, stigmasterol seems to have potential beneficial effects on the treatment of type 2 diabetes mellitus with the probable mechanism of targeting GLUT4 glucose transporter included increasing GLUT4 translocation and expression.

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Section: Discussionmentioning

confidence: 99%

Anti-diabetic activity of stigmasterol from soybean oil by targeting the GLUT4 glucose transporter

Wang

Yang

et al. 2017

Food & Nutrition Research

100

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“…GS, the rate-limiting enzyme for glycogen synthesis, displays enhanced activity ratio when isolated from previously exercised muscle. This suggests that the enzyme becomes dephosphorylated in response to exercise (12), as reviewed by Ivy and Kuo (13). Recently it was reported that treadmill running leads to deactivation of GSK3␣ and GSK3␤ in rat skeletal muscle concurrent with GS activation (8).…”

Section: Regulation Of Glycogen Synthase Kinase-3 In Human Skeletal Mmentioning

confidence: 95%

Regulation of Glycogen Synthase Kinase-3 in Human Skeletal Muscle

et al. 2001

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Studies of skeletal muscle from rodents performed both in vivo and in vitro suggest a regulatory role of glycogen synthase kinase (GSK) 3 in glycogen synthase (GS) activation in response to insulin. Recently, hyperinsulinemic clamp studies in humans support such a role under nearly physiological conditions. In addition, in rats the activation of GS in skeletal muscle during treadmill running is time-related to the deactivation of GSK3. We investigated whether GSK3 was deactivated in human muscle during low-(~50% VO 2max for 1.5 h) and high-intensity (~75% VO 2max for 1 h) bicycle exercise as well as food intake. We observed a small but significant increase in GSK3␣ (10-20%) activity in biopsies obtained from vastus lateralis after both lowand high-intensity exercise, whereas GSK3␤ activity was unaffected. Subsequent food intake increased Aktphosphorylation (~2-fold) and deactivated GSK3␣ (~40%), whereas GSK3␤ activity was unchanged. GS activity increased in response to both exercise and food intake. We conclude that GSK3␣ but not GSK3␤ may have a role in the regulation of GS activity in response to meal-associated hyperinsulinemia in humans. However, in contrast to findings in muscle from rats, exercise does not deactivate GSK3 in humans, suggesting a GSK3-independent mechanism in the regulation of GS activity in muscle during physical activity. Diabetes 50:265-269, 2001 G lycogen synthase kinase (GSK) 3 is expressed in skeletal muscle and has been identified in two isoforms, ␣ and ␤. Both isoforms contain potential serine and tyrosine phosphorylation sites. Tyrosine phosphorylation is important for full activation, but the regulatory role for these sites in vivo is still unclear (1-3). Serine phosphorylation on sites 9 and 21 in GSK3␤ and GSK3␣, respectively, is highly regulated in response to stimulation (e.g., by insulin) and phosphorylation on these sites leads to deactivation of the enzyme (4-6). In vitro GSK3phosphorylates two of the four sites on glycogen synthase (GS), which also become dephosphorylated in response to insulin (7). This suggests that insulin activates GS in part through a GSK3-dependent mechanism. Supporting this view are our recent observations that the time course of serine phosphorylation and deactivation of GSK3 and activation of GS is highly identical under both supraphysiological insulin stimulation in the rat (8) and during physiological insulin clamp conditions in humans (9). Interestingly, during physiological conditions in humans only GSK3␣ is deactivated by insulin, whereas supraphysiological insulin injection in the rat leads to deactivation of both GSK3␣ and GSK3␤ (8-10).In the period after exercise, glycogen resynthesis is a major metabolic challenge for the skeletal muscle. Sustained activation of glucose uptake and activation of GS together with enhanced insulin sensitivity for activation of these processes eventually lead to normalization or even supercompensation of the glycogen stores after exercise, as reviewed by Richter (11). GS, the rate-limiting enzyme for glycogen...

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“…It is also possible that contractile activity can directly activate or prime GLUT4 vesicular proteins or glycogen synthase associated proteins involved in regulation of the glucose transporter system and glycogen synthase activity, respectively. In rats, there is an inverse relationship between muscle glycogen content and exercise-and insulin-induced glucose transport and GLUT4 translocation as well as glycogen synthase activity (1, [47][48][49][50]. Therefore, the level of glycogen depletion in the muscle may also be a major determinant for the exercise-induced increase in insulin sensitivity for glucose transport, GLUT4 translocation (10), and glycogen synthase activation.…”

Section: Discussionmentioning

confidence: 99%

Insulin signaling and insulin sensitivity after exercise in human skeletal muscle.

Wojtaszewski

Hansen²,

Gade³

et al. 2000

Diabetes

321

292

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Muscle glucose uptake, glycogen synthase activity, and insulin signaling were investigated in response to a physiological hyperinsulinemic (600 p m o l / l ) -e u g l y c e m i c clamp in young healthy subjects. Four hours before the clamp, the subjects performed one-legged exercise for 1 h. In the exercised leg, insulin more rapidly activated glucose uptake (half activation time [t 1 / 2 ] = 11 vs. 3 4 min) and glycogen synthase activity (t 1 / 2 = 8 vs. 17 min), and the magnitude of increase was two-to fourfold higher compared with the rested leg. However, prior exercise did not result in a greater or more rapid increase in insulin-induced receptor tyrosine kinase ( I RTK) activity (t 1 / 2 = 50 min), serine phosphorylation of Akt (t 1 / 2 = 1-2 min), or serine phosphorylation of glycogen synthase kinase-3 (GSK-3) (t 1 / 2 = 1-2 min) or in a larger or more rapid decrease in GSK-3 activity (t 1 / 2 = 3-8 min). Thirty minutes after cessation of insulin infusion, glucose uptake, glycogen synthase a c t i v i t y, and signaling events were partially reversed in both the rested and the exercised leg. We conclude the following: 1) physiological hyperinsulinemia induces sustained activation of insulin-signaling molecules in human skeletal muscle; 2) the more distal insulinsignaling components (Akt, GSK-3) are activated much more rapidly than the proximal signaling molecules (1). In human skeletal muscle, the effects of exercise per se on muscle glucose transport are relatively short-lived (2-4 h), whereas the enhanced sensitivity for glucose transport activation by insulin has been observed >48 h after an exercise bout in human subjects (3-5). In rat skeletal muscle, it has been demonstrated that there is a marked increase in insulin sensitivity for both glucose transport and glycogen synthase activation after exercise (2,6). These changes facilitate glycogen resynthesis, and they may be the mechanism by which muscle glycogen storage is increased above pre-exercise values, known as "supercompensation" (7,8). Whether prior exercise also increases the sensitivity for glycogen synthase activation by insulin in human skeletal muscle is unknown.We have previously hypothesized that an upregulation of insulin signaling is involved in the increased insulin sensitivity after exercise (9). However, if humans are subjected to physiological hyperinsulinemia or if rat muscles are incubated in the presence of insulin 3-4 h after exercise, insulin receptor tyrosine kinase (IRTK) a c t i v i t y, insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation, and phosphatidylinositol (PI) 3-kinase activity are not enhanced in skeletal muscle (9,10). This suggests that exercise may modulate insulin signaling further downstream or affect processes directly involved in glucose transporter translocation and activation.Signaling involving D-3 phosphorylated inositol lipids, generated by the action of PI 3-kinases, has been suggested to lead to the metabolic effects of insulin, including the activation of glucose transport and glycogen sy...

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Regulation of GLUT4 protein and glycogen synthase during muscle glycogen synthesis after exercise

Cited by 105 publications

References 46 publications

Anti-diabetic activity of stigmasterol from soybean oil by targeting the GLUT4 glucose transporter

Anti-diabetic activity of stigmasterol from soybean oil by targeting the GLUT4 glucose transporter

Regulation of Glycogen Synthase Kinase-3 in Human Skeletal Muscle

Insulin signaling and insulin sensitivity after exercise in human skeletal muscle.

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