Effects of epinephrine on insulin-stimulated glucose uptake and GLUT-4 phosphorylation in muscle

Lee, A. D.; Hansen, Polly A.; Schluter, Jane Marie; Gulve, E. A.; Gao, Jiaping; Holloszy, John O.

doi:10.1152/ajpcell.1997.273.3.c1082

Cited by 63 publications

(57 citation statements)

References 22 publications

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“…Most likely PDE3B which is a membrane associated enzyme [3] regulates a cAMP pool different from a pool regulated by PDE4, an enzyme found mainly in the cytosolic fraction of adipocytes [28]. In a number of other cell types [44][45][46] and in several PDE3 and PDE4 knock out mice models [47][48][49] A correlation between cAMP-mediated inhibition of insulin-induced glucose uptake and inhibition of translocation of GLUT-4 to the plasma membrane has been shown in some studies [8] but not in others [6]. Isoproterenol-induced inhibition of insulin-induced glucose uptake in the presence of ADA was suggested to be caused by trapping of GLUT-4 in occluded vesicles associated with the plasma membrane during exocytosis, rather than by reduction of total plasma membrane GLUT-4 content [6].…”

Section: Discussionmentioning

confidence: 95%

“…However, different effects of these agents have been reported. Thus, cAMP-increasing β-adrenergic agonists have been shown to increase [6,7], to have no effect on [8,9], or to decrease [10][11][12] insulin-induced glucose uptake in adipocytes. Studies using PDE3 inhibitors, OPC3911 and cilostamide, showed impaired, [13,14] or unaffected [15] insulin-induced glucose uptake in adipocytes.…”

Section: Introductionmentioning

confidence: 99%

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Role of PDE3B in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis in primary rat adipocytes

Zmuda-Trzebiatowska

Oknianska

Manganiello

et al. 2006

Cellular Signalling

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In adipocytes, phosphorylation and activation of PDE3B is a key event in the antilipolytic action of insulin. The role of PDE4, another PDE present in adipocytes, is not yet known. In this work we investigate the role of PDE3B and PDE4 in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis. Inhibition of PDE3 (OPC3911, milrinone) but not PDE4 (RO 20-1724) lowered insulin-induced glucose uptake and lipogenesis, especially in the presence of isoproterenol (a general β-adrenergic agonist), CL316243, a selective β3-adrenergic agonist, and pituitary adenylate cyclase-activating peptide. The inhibitory effect of OPC3911 was associated with reduced translocation of GLUT-4 from the cytosol to the plasma membrane. Both OPC3911 and RO 20-1724 increased protein kinase A (PKA) activity and lipolysis. H89, a PKA inhibitor, did not affect OPC3911-mediated inhibition of insulin-induced glucose uptake and lipogenesis, whereas 8-pCPT-2'-O-Me-cAMP, an Epac agonist which mediates PKA independent cAMP signaling events, mimicked all the effects of OPC3911. Insulin-mediated activation of protein kinase B, a kinase involved in insulininduced glucose uptake, was apparently not altered by OPC3911. In summary, our data suggest that PDE3B, but not PDE4, contributes to the regulation of insulin-induced glucose uptake, GLUT-4 translocation, and lipogenesis presumably by regulation of a cAMP/ Epac signalling mechanisms.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Role of PDE3B in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis in primary rat adipocytes

Zmuda-Trzebiatowska

Oknianska

Manganiello

et al. 2006

Cellular Signalling

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“…The administration of supra-physiological concentrations of adrenaline increases GLUT4 translocation and decreases 3-O-methyl glucose transport in perfused rat muscle, thus implying a decrease in GLUT4 intrinsic activity (Bonen et al 1992). In contrast, b-adrenergic stimulation does not directly inhibit insulin-stimulated (Lee et al 1997;Aslesen & Jensen, 1998) or contraction-stimulated (Aslesen & Jensen, 1998) glucose transport in vitro. Taken together, these findings suggest that adrenaline-mediated decreases in glucose uptake by skeletal muscle are likely to be due to a reduction in glucose phosphorylation and a subsequent inhibition of transport.…”

Section: Discussionmentioning

confidence: 98%

“…Studies conducted in vitro support such a mechanism (Chiasson et al 1981;Aslesen & Jensen, 1998). In contrast, most studies have observed that both insulin- (Lee et al 1997;Aslesen & Jensen, 1998) and contraction-(Aslesen & Jensen, 1998) stimulated glucose transport in vitro are unaffected by b-adrenergic stimulation, although this remains equivocal (Bonen et al 1992). Hence previous studies suggest a role for adrenaline in inhibiting glucose uptake via decreased glucose transport secondary to an inhibition of glucose phosphorylation.…”

mentioning

confidence: 97%

Adrenaline increases skeletal muscle glycogenolysis, pyruvate dehydrogenase activation and carbohydrate oxidation during moderate exercise in humans

Watt

Howlett

Febbraio

et al. 2001

The Journal of Physiology

137

103

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Muscle glycogen degradation is catalysed by glycogen phosphorylase, which exists in a less active b and more active a form. During exercise, transformation of phosphorylase b to a is regulated by increases in cytosolic Ca 2+ , liberated during muscle contraction, and an adrenaline-mediated increase in 3fi,5fi-cyclic adenosine monophosphate (cAMP), thereby setting an upper limit for muscle glycogenolysis (Howlett et al. 1998). Factors linked to the energy state of the cell (e.g. AMP and IMP) or substrate (glycogen, inorganic phosphate -P i ) then 'fine-tune' the flux rate according to the metabolic demands (Ren & Hultman, 1990;Johnson, 1992).Increased adrenaline often (Jansson et al. 1986;Spriet et al. 1988;Febbraio et al. 1998), but not always (Chesley et al. 1995;Wendling et al. 1996), results in increased muscle glycogen utilisation during exercise in man. The discrepancies in these studies may be related to the infusion of supraphysiological concentrations of adrenaline (Jansson et al. 1986;Spriet et al. 1988) and/or the marked differences in exercise intensity (Chesley et al. 1995;Febbraio et al. 1998). During exercise where the energy state of the cell is challenged (Chesley et al. 1995), factors such as increased P i , and allosteric modulation via increased free AMP (AMP f ) may maximally activate 1. To evaluate the role of adrenaline in regulating carbohydrate metabolism during moderate exercise, 10 moderately trained men completed two 20 min exercise bouts at 58 ± 2 % peak pulmonary oxygen uptake (V O 2 ,peak ). On one occasion saline was infused (CON), and on the other adrenaline was infused intravenously for 5 min prior to and throughout exercise (ADR). ; means ± S.E.M.) and this effect was maintained throughout exercise. Total carbohydrate oxidation increased by 18 % and this effect was due to greater skeletal muscle glycogenolysis (P < 0.05) and pyruvate dehydrogenase (PDH) activation (P < 0.05, treatment effect). Glucose rate of appearance was not different between trials, but the infusion of adrenaline decreased (P < 0.05, treatment effect) skeletal muscle glucose uptake in ADR.3. During exercise muscle glucose 6-phosphate (G-6-P) (P = 0.055, treatment effect) and lactate (P < 0.05) were elevated in ADR compared with CON and no changes were observed for pyruvate, creatine, phosphocreatine, ATP and the calculated free concentrations of ADP and AMP.4. The data demonstrate that elevated plasma adrenaline levels during moderate exercise in untrained men increase skeletal muscle glycogen breakdown and PDH activation, which results in greater carbohydrate oxidation. The greater muscle glycogenolysis appears to be due to increased glycogen phosphorylase transformation whilst the increased PDH activity cannot be readily explained. Finally, the decreased glucose uptake observed during exercise in ADR is likely to be due to the increased intracellular G-6-P and a subsequent decrease in glucose phosphorylation.

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“…␤-Adrenergic action and cAMP have been implicated as negative regulators of insulin action (20,23,26,38,43). GS, the rate-limiting enzyme for the storage of intracellular glucose as glycogen in skeletal muscle (25), is activated in the presence of insulin and inhibited by agents that increase intracellular cAMP concentrations ([cAMP]) (7,25,38).…”

mentioning

confidence: 99%

Levodopa with carbidopa diminishes glycogen concentration, glycogen synthase activity, and insulin-stimulated glucose transport in rat skeletal muscle

Smith¹,

Ju²,

Saha³

et al. 2004

Journal of Applied Physiology

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. Levodopa with carbidopa diminishes glycogen concentration, glycogen synthase activity, and insulin-stimulated glucose transport in rat skeletal muscle. J Appl Physiol 97: 2339 -2346, 2004; doi:10.1152/japplphysiol.01219.2003.-We hypothesized that levodopa with carbidopa, a common therapy for patients with Parkinson's disease, might contribute to the high prevalence of insulin resistance reported in patients with Parkinson's disease. We examined the effects of levodopa-carbidopa on glycogen concentration, glycogen synthase activity, and insulin-stimulated glucose transport in skeletal muscle, the predominant insulin-responsive tissue. In isolated muscle, levodopa-carbidopa completely prevented insulin-stimulated glycogen accumulation and glucose transport. The levodopa-carbidopa effects were blocked by propranolol, a ␤-adrenergic antagonist. Levodopa-carbidopa also inhibited the insulin-stimulated increase in glycogen synthase activity, whereas propranolol attenuated this effect. Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate (IRS)-1 was reduced by levodopa-carbidopa, although Akt phosphorylation was unaffected by levodopacarbidopa. A single in vivo dose of levodopa-carbidopa increased skeletal muscle cAMP concentrations, diminished glycogen synthase activity, and reduced tyrosine phosphorylation of IRS-1. A separate set of rats was treated intragastrically twice daily for 4 wk with levodopa-carbidopa. After 4 wk of treatment, oral glucose tolerance was reduced in rats treated with drugs compared with control animals. Muscles from drug-treated rats contained at least 15% less glycogen and ϳ50% lower glycogen synthase activity compared with muscles from control rats. The data demonstrate ␤-adrenergic-dependent inhibition of insulin action by levodopa-carbidopa and suggest that unrecognized insulin resistance may exist in chronically treated pa-

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Effects of epinephrine on insulin-stimulated glucose uptake and GLUT-4 phosphorylation in muscle

Cited by 63 publications

References 22 publications

Role of PDE3B in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis in primary rat adipocytes

Role of PDE3B in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis in primary rat adipocytes

Adrenaline increases skeletal muscle glycogenolysis, pyruvate dehydrogenase activation and carbohydrate oxidation during moderate exercise in humans

Levodopa with carbidopa diminishes glycogen concentration, glycogen synthase activity, and insulin-stimulated glucose transport in rat skeletal muscle

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