Adrenergic receptor stimulation attenuates insulin-stimulated glucose uptake in 3T3-L1 adipocytes by inhibiting GLUT4 translocation

Abstract

Activation of the sympathetic nervous system inhibits insulin-stimulated glucose uptake. However, the underlying mechanisms are incompletely understood. Therefore, we studied the effects of catecholamines on insulin-stimulated glucose uptake and insulin-stimulated translocation of GLUT4 to the plasma membrane in 3T3-L1 adipocytes. We found that epinephrine (1 microM) nearly halved insulin-stimulated 2-deoxyglucose uptake. The beta-adrenoceptor antagonist propranolol (0.3 microM) completely antagonized the inhibitory effect of epinephrine on insulin-stimulated glucose uptake, whereas the alpha-adrenoceptor antagonist phentolamine (10 microM) had no effect. When norepinephrine was used instead of epinephrine, the results were identical. None of the individual selective beta-adrenoceptor antagonists (1 microM, beta(1): metoprolol, beta(2): ICI-118551, beta(3): SR-59230A) could counteract the inhibitory effect of epinephrine. Combination of ICI-118551 and SR-59230A, as well as combination of all three selective beta-adrenoceptor antagonists, abolished the effect of epinephrine on insulin-stimulated glucose uptake. After differential centrifugation, we measured the amount of GLUT1 and GLUT4 in the plasma membrane and in intracellular vesicles by means of Western blotting. Both epinephrine and norepinephrine reduced insulin-stimulated GLUT4 translocation to the plasma membrane. These results show that beta-adrenergic (but not alpha-adrenergic) stimulation inhibits insulin-induced glucose uptake in 3T3-L1 adipocytes, most likely via the beta(2)- and beta(3)-adrenoceptor by interfering with GLUT4 translocation from intracellular vesicles to the plasma membrane.

Verification of the Antidiabetic Effects of Cinnamon (Cinnamomum zeylanicum) Using Insulin-Uncontrolled Type 1 Diabetic Rats and Cultured Adipocytes

“…35) Of the events connecting the administration of CE and the observed phenomena, we are about to verify details of the mechanism related to excitation of the central nervous system and AMPK activity. 36,37) In conclusion, CE had two major functions: i) it up-regulated mitochondrial UCP-1, and ii) enhanced the production and translocation of GLUT4 in the muscle and, at least, the translocation of GLUT4 in adipose tissues. These activities may allow cinnamon to be used in the daily care of diabetes mellitus by its dietary or supplementary use, and in alleviating the long-term complications, including cardiovascular disease, chronic renal failure and retinal damage.…”

New Insights into Cytosolic Glucose Levels during Differentiation of 3T3-L1 Fibroblasts into Adipocytes

“…Several mechanisms have been proposed by which ␤-adrenergic receptor stimulation may affect insulin-stimulated glucose uptake in 3T3-L1 and rat adipocytes (12,(31)(32)(33)(34).…”

“…6G, right plot). It has been shown that insulin-stimulated glucose uptake in rat and 3T3-L1 adipocytes could be reduced upon treatment with adrenaline, nor-adrenaline, and isoproterenol (33)(34)(35)(36). Some studies report that ␤-adrenergic receptor agonists attenuate insulin-stimulated glucose uptake by decreasing the translocation of GLUT4 in rat and 3T3-L1 adipocytes (31,34).…”

“…It has been shown that insulin-stimulated glucose uptake in rat and 3T3-L1 adipocytes could be reduced upon treatment with adrenaline, nor-adrenaline, and isoproterenol (33)(34)(35)(36). Some studies report that ␤-adrenergic receptor agonists attenuate insulin-stimulated glucose uptake by decreasing the translocation of GLUT4 in rat and 3T3-L1 adipocytes (31,34). Other studies (37) report that the binding of insulin to its receptor is attenuated, which probably results in a less stimulatory signal and, as a consequence, in a reduced increase in the rate of glucose uptake.…”

Chronic caffeine intake reverses age-induced insulin resistance in the rat: effect on skeletal muscle Glut4 transporters and AMPK activity

“…Increased circulating catecholamines contribute to insulin resistance mainly by stimulating lipolysis in adipose tissue, leading to an increase in circulating nonesterified fatty acids (NEFA) (Lafontan and Langin 2009), and by stimulating both gluconeogenesis and glycogenolysis, contributing to increased hepatic glucose production (Exton and Park 1968;Exton et al 1972). This increase in endogenous glucose production associated with decreased skeletal muscle glucose uptake and decreased fatty acid oxidation (Young et al 1985;Acheson et al 2004;Mulder et al 2005) leads to hyperglycemia and tissue triglyceride deposition, major pathophysiological hallmarks of insulin resistance. We have recently shown that chronic caffeine intake prevents the development of insulin resistance and decreases circulating catecholamines in diet-induced insulin-resistant rats (Conde et al 2012).…”