Exercise-Induced Increase in Glucose Transporters in Plasma Membranes of Rat Skeletal Muscle*

Douen, Andre G.; Ramlal, Toolsie; Klip, Amira; Young, Douglas A.; Cartee, Gregory D.; Holloszy, John O.

doi:10.1210/endo-124-1-449

Cited by 125 publications

(70 citation statements)

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“…p38 MAPK␣ and p38 MAPK␤ are activated by electrically-induced contraction. Contraction is a potent stimulator of glucose uptake in muscle (24), yet the signaling pathway linking contraction to glucose transporters is still unknown. Several enzymes have been shown to be activated and/or phosphorylated in exercising and/or contracting mus- …”

Section: R Somwar and Associatesmentioning

confidence: 99%

Activation of p38 mitogen-activated protein kinase alpha and beta by insulin and contraction in rat skeletal muscle: potential role in the stimulation of glucose transport.

et al. 2000

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The stress-activated p38 mitogen-activated protein kinase (MAPK) was recently shown to be activated by insulin in muscle and adipose cells in culture. Here, we explore whether such stimulation is observed in rat skeletal muscle and whether muscle contraction can also affect the enzyme. Insulin injection (2 U over 3.5 min) resulted in increases in p38 MAPK phosphorylation measured in soleus (3.2-fold) and quadriceps (2.2-fold) muscles. Increased phosphorylation (3.5-fold) of an endogenous substrate of p38 MAPK, cAMP response element binder (CREB), was also observed. After in vivo insulin treatment, p38 MAPK␣ and p38 MAPK␤ isoforms were found to be activated (2.1-and 2.4-fold, respectively), using an in vitro kinase assay, in immunoprecipitates from quadriceps muscle extracts. In vitro insulin treatment (1 nmol/l over 4 min) and electrically-induced contraction of isolated extensor digitorum longus (EDL) muscle also doubled the kinase activity of p38 MAPK␣ and p38 MAPK␤. The activity of both isoforms was inhibited in vitro by 10 µmol/l SB203580 in all muscles. To explore the possible participation of p38 MAPK in the stimulation of glucose uptake, EDL and soleus muscles were exposed to increasing doses of SB203580 before and during stimulation by insulin or contraction. SB203580 caused a significant reduction in the insulin-or contractionstimulated 2-deoxyglucose uptake. Maximal inhibition (50-60%) occurred with 10 µmol/l SB203580. These results show that p38 MAPK␣ and -␤ isoforms are activated by insulin and contraction in skeletal muscle. The data further suggest that activation of p38 MAPK may participate in the stimulation of glucose uptake by both stimuli in rat skeletal muscle.

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Section: R Somwar and Associatesmentioning

confidence: 99%

Activation of p38 mitogen-activated protein kinase alpha and beta by insulin and contraction in rat skeletal muscle: potential role in the stimulation of glucose transport.

et al. 2000

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“…Data shown are the average Ϯ standard deviation of three independent experiments. translocation and glucose uptake (16,17,36,42,49,53). Although the mechanism of exercise-contraction stimulation is not known, this process occurs independently of PI 3-kinase function (30,31,50).…”

Section: Fig 8 Vamp3mentioning

confidence: 99%

VAMP3 Null Mice Display Normal Constitutive, Insulin- and Exercise-Regulated Vesicle Trafficking

Yang¹,

Mora²,

Ryder³

et al. 2001

Molecular and Cellular Biology

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To investigate the physiological function of the VAMP3 vesicle SNARE (v-SNARE) isoform in the regulation of GLUT4 vesicle trafficking, we generated homozygotic VAMP3 null mice by targeted gene disruption. The VAMP3 null mice had typical growth rate and weight gain, with normal maintenance of fasting serum glucose and insulin levels. Analysis of glucose disposal and insulin sensitivity demonstrated normal insulin and glucose tolerance, with no evidence for insulin resistance. Insulin stimulation of glucose uptake in isolated primary adipocytes was essentially the same for the wild-type and VAMP3 null mice. Similarly, insulin-, hypoxia-, and exercise-stimulated glucose uptake in isolated skeletal muscle did not differ significantly. In addition, other general membrane trafficking events including phagocytosis, pinocytosis, and transferrin receptor recycling were also found to be unaffected in the VAMP3 null mice. Taken together, these data demonstrate that VAMP3 function is not necessary for either regulated GLUT4 translocation or general constitutive membrane recycling.Insulin increases glucose uptake in adipose and striated muscle tissues primarily by recruiting the GLUT4 glucose transporter protein to the cell surface (37). In the basal noninsulin-stimulated state, the majority of GLUT4 resides in one or more intracellular compartments (44,45). Upon addition of insulin, the signaling cascade triggered by the insulin receptor leads to rapid translocation of the GLUT4 transporter to the plasma membrane, thereby increasing the number of transporters at the cell surface and the rate of glucose uptake (12,27,38,41).The process of GLUT4 translocation shares important features with the exocytosis of synaptic vesicles during neurotransmitter release. For example, the plasma membrane docking and fusion of GLUT4 vesicles appears to require the t-SNARE protein isoforms syntaxin 4 and SNAP23 (9,37,48). GLUT4 vesicles contain the v-SNARE-interacting partners VAMP2 and VAMP3, both of which translocate to the plasma membrane in parallel with GLUT4 (33,47). Recent studies using various toxins and endosomal ablation techniques have indicated that VAMP2 is the predominant v-SNARE responsible for insulin-stimulated GLUT4 translocation in cultured 3T3-L1 adipocytes and in the L6 muscle cell line (9,32,33,40). In contrast, guanosine-5Ј-O-(3-thiotriphosphate) (GTP␥S)-stimulated GLUT4 translocation was found to be dependent on VAMP3, thereby suggesting the presence of two independently regulated pools of GLUT4 storage compartments (35). In this regard, skeletal muscle has also been shown to contain two pools of GLUT4 vesicles, one that responds to insulin and another that is responsive to exercise and contraction (1,11,39).In addition, the skeletal muscle exercise-contraction subpopulation utilizes a signaling pathway independent of the phosphatidylinositol (PI) 3-kinase (30, 31, 50). Similarly, GTP␥S stimulation in adipocytes is also independent of the PI 3-kinase, suggesting that the GTP␥S and exercise-contraction pathways may util...

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“…Muscle contraction is another powerful trigger for glucose metabolism (34,35) and provides an additional, potential compensatory mechanism whereby mice deficient in muscle Insr signaling can overcome insulin resistance. Indeed, contraction-stimulated glucose uptake in MIRKO mice is normal (36).…”

mentioning

confidence: 99%

Lilly Lecture 2003

2004

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Type 2 diabetes arises from a combination of impaired insulin action and defective pancreatic ␤-cell function. Classically, the two abnormalities have been viewed as distinct yet mutually detrimental processes. The combination of impaired insulin-dependent glucose metabolism in skeletal muscle and impaired ␤-cell function causes an increase of hepatic glucose production, leading to a constellation of tissue abnormalities that has been referred to as the diabetes "ruling triumvirate." Targeted mutagenesis in mice has led to a critical reappraisal of the integrated physiology of insulin action. These studies indicate that insulin resistance in skeletal muscle and adipose tissue does not necessarily lead to hyperglycemia, so long as insulin sensitivity in other tissues is preserved. Additional data suggest a direct role of insulin signaling in ␤-cell function and regulation of ␤-cell mass, thus raising the possibility that insulin resistance may be the overarching feature of diabetes in all target tissues. I propose that we replace the original picture of a ruling triumvirate with that of a squabbling republic in which every tissue contributes to the onset of the disease. Diabetes 53: [1633][1634][1635][1636][1637][1638][1639][1640][1641][1642] 2004 T he classic view of the development of type 2 diabetes is that skeletal muscle (1) and adipose tissue (2) are resistant-be it on a genetic or on an environmental basis-to insulin-dependent glucose uptake and nonoxidative disposal (3). However, the onset of hyperglycemia reflects two separate events occurring at different sites, namely a failure of the ␤-cell's compensatory ability (4) with an attendant rise in hepatic glucose production (5). In this context, hyperglycemia is viewed as a vicarious mechanism to promote peripheral glucose utilization by mass action, in the face of insulin resistance ( Fig. 1) (6). The paradox implicit in this view is that, whereas insulin resistance occurs primarily in muscle and adipose tissue, diabetes is actually a disease of liver and ␤-cells, which do not appear to be primary targets of insulin resistance. One school of thought contends that metabolic mediators engendered by the insulin-resistant muscle and fat cause metabolic abnormalities in liver and ␤-cells (Fig. 2). There is ample experimental evidence to support this view (7,8) and no shortage of candidate mediators of insulin resistance (9). However, a different mechanism has begun to emerge from studies of mice with targeted gene mutations, namely that liver and ␤-cell are primary sites of insulin resistance. This question bears on the therapeutic approach to diabetes, for if the response of the liver and the ␤-cell observed in insulin-resistant individuals is indeed a compensatory one, then we should endeavor to preserve it. If, on the other hand, the liver and ␤-cell response is detrimental to long-term preservation of insulin sensitivity, then we should redouble our efforts to treat diabetes by acting on insulin resistance at those sites. The elusive genetics of insulin...

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Exercise-Induced Increase in Glucose Transporters in Plasma Membranes of Rat Skeletal Muscle*

Cited by 125 publications

References 0 publications

Activation of p38 mitogen-activated protein kinase alpha and beta by insulin and contraction in rat skeletal muscle: potential role in the stimulation of glucose transport.

Activation of p38 mitogen-activated protein kinase alpha and beta by insulin and contraction in rat skeletal muscle: potential role in the stimulation of glucose transport.

VAMP3 Null Mice Display Normal Constitutive, Insulin- and Exercise-Regulated Vesicle Trafficking

Lilly Lecture 2003

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