Inhibitory Effect of Epinephrine on Insulin-stimulated Glucose Uptake by Rat Skeletal Muscle

Epinephrine and b-adrenergic stimulation rapidly inhibit insulin-mediated glucose uptake by induction of insulin resistance mainly in the skeletal muscle [1,2]. The insulin signalling pathway may be altered by b-adrenergic stimulation both by cAMP and cAMP independent mechanisms [3]. An inhibitory action at multiple sites is suggested since the insulin signal is disturbed at the receptor level [4] as well as in the tyrosine kinase [5], the glucose transporter protein [6] and the glycolytic pathway [7]. Moreover, induction of lipolysis by b-adrenergic stimuli leads to decreased oxidation of glucose through the action of the Randle cycle [8].The glucose transporter protein is considered to be rate-limiting for insulin-stimulated glucose uptake in the muscle. Moreover, recent research has emphasized the importance of the capillary wall as a major determinant of the transendothelial delivery of glucose [9] and insulin [10] in skeletal muscle since the interstitial concentrations of glucose and insulin are lower than those in the arterial plasma [9,10]. This is further supported by the findings that the insulin-[11] and glucose-[12] stimulated increase in muscle blood flow correlates with glucose uptake in normal as well as in insulin resistant muscles [13].The importance of blood flow for the rate of delivery of glucose and insulin to the muscles is, however, Diabetologia (1998) Summary Muscle glucose uptake and lactate release during b-adrenergic stimulation by epinephrine (epi) and b-adrenergic blockade by propranolol (prop) were investigated during an euglycaemic hyperinsulinaemic (30 pmol × kg ±1 × min ±1 ) with or without added somatostatin (0.1 mg/min; pancreatic) clamp in female rats. To assess the interstitial insulin, glucose and lactate concentrations, microdialysis was done in the medial femoral muscle in both legs. The influence of muscle skeletal blood flow on interstitial insulin, glucose and lactate was examined with the microsphere technique, using 57 Co-microspheres. Epinephrine decreased glucose infusion rate by about 75 % (p < 0.0001) and increased concentrations of interstitial glucose by about 35 % (p < 0.001) and lactate by about 65 % (p < 0.01). Plasma insulin concentration increased during b-adrenergic stimulation by about 25 % (p < 0.05) whereas the interstitial insulin concentration was unchanged. Muscle blood flow in the hindlimb was considerably enhanced by about 130 %, (p < 0.001) by epinephrine. Infusion of propranolol totally abolished all the above effects induced by epinephrine. The data show that insulin resistance and vasodilation induced by b-adrenergic stimulation with epinephrine is accompanied by increased interstitial glucose as well as lactate concentrations in muscle. The increased interstitial glucose concentration is the result of a decreased cellular uptake of glucose together with an increased capillary delivery of glucose by vasodilation. It is concluded that the severe cellular resistance to insulin induced by epinephrine could not be overcome either by the increased...

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Induction of rat muscle insulin resistance by epinephrine is accompanied by increased interstitial glucose and lactate concentrations

1998

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“…Deibert and DeFronzo [25] reported that epinephrine impaired the tissue sensitivity to insulin by using the hyperinsulinemic euglycemic clamp technique. Chiasson et al [26] indicated that epinephrine suppressed the insulinstimulated glucose uptake in perfused hindlimbs of rats. Moreover,Lupien et al [8] provided evidence that chronic norepinephrine infusion was associated with increased basal glucose turnover and increased insulin sensitivity of peripheral tissue in rats by means of the euglycemic clamp technique.…”

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“…One proposed mechanism for the increased glucose uptake in skeletal muscle of ADMX rat is lowered muscle glycogen content and increased glycogen synthase activity [8,26]. Recently, Marette and Bukowiecki [7] showed that norepinephrine (10-8M) significantly potentiated submaximal insulin responses for glucose transport in isolated rat brown adipocytes.…”

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confidence: 99%

Effects of Adrenodemedullation on In Vivo Insulin-Stimulated Glucose Utilization in Relation to Glycolysis in Rat Peripheral Tissue.

et al. 1993

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Abstract. The effect of adrenodemedullation (ADMX) on insulin action was examined in anesthetized rats by means of a three-step euglycemic clamp procedure (insulin infusion rate: 0, 6.0 and 30.0 mU•kgBW-1•min-1) combined with a microdialysis technique in skeletal muscle and adipose tissue. The dialysate lactate levels in the above tissues increased in parallel with the plasma lactate levels during the sequential euglycemic clamp. In the euglycemic clamp, the glucose infusion rate (GIR) was significantly (P<0.01) higher in ADMX rats (13.41±0.82 mg•kgBW-1•min-1) than in SHAM rats (10.21±0.87 mg•kgBW-1•min-1) during the 6.0-mU•kgBW-1•min-1 insulin infusion, and the lack of a significant difference between ADMX and SHAM rats was observed during the 30-mU•kgBW-1 •min-1 insulin infusion. In skeletal muscle, the concentration of lactate in dialysate was significantly higher in ADMX rats (9.29±1.01 mg/dl) than in SHAM rats (6.22±0.47 mg/dl) (P<0.05) at an insulin infusion rate of 6.OmU•kgBW-1•min-1. In adipose tissue, no significant difference in dialysate lactate levels was found between ADMX and SHAM rats at any insulin infusion rate. These results suggest that 1) it is possible to determine insulin action in skeletal muscle and adipose tissue in vivo by using the microdialysis technique, that 2) ADMX appears to result in a significant increase in insulin sensitivity, and that 3) lactate formation increased in skeletal muscle, but not in adipose tissue. Correspondence to: Dr. Yoshiharu OSHIDA, Research Center of Health, Physical Fitness and Sports, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-01, Japan maximal insulin response for glucose transport in rat [7], and that chronic fJ-adrenoreceptor stimulation with norepinephrine increases insulin-stimulating glucose disposal in vivo by increasing the insulin sensitivity of rat peripheral tissues [8].It has been known that plasma levels of norepinephrine are increased and those of epinephrine are decreased one week after ADMX in rats [9]. Under these conditions it could be hypothesized that insulin-stimulated glucose uptake is increased in peripheral tissue in vivo considering the above previous reports [7, 8, 9]. In order to confirm this hypothesis, we have used a sequential euglycemic hyperinsulinemic clamp technique, adapted in our laboratory for use in rats, in combination with a microdialysis technique

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“…6 -8 ' 21 ' 22 Catecholamines, indeed, display potent metabolic effects. 23 - 29 Particularly, suppression of insulin secretion by catecholamines is mediated through a-adrenergic receptors, 25 whereas in human subjects, the direct effects of catecholamines on periph-eral and hepatic glucose metabolism appear to be mediated largely through /3-adrenergic receptors. 26 Acute /3-adrenergic stimulation results in impaired insulin action, mainly through the decrease in net glycogen deposition (stimulation of glycogen phosphorylase and inhibition of glycogen synthase) and the increase in hepatic glucose output.…”

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“…26 Acute /3-adrenergic stimulation results in impaired insulin action, mainly through the decrease in net glycogen deposition (stimulation of glycogen phosphorylase and inhibition of glycogen synthase) and the increase in hepatic glucose output. 23 - 29 However, the effect of the chronic elevation of the plasma catecholamine concentration on insulin action is still controversial. Some discrepancies between a-and /3-adrenergic responsiveness have been demonstrated when adrenergic sensitivity in hypertension was examined.…”

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Increased insulin sensitivity in the high sodium one-kidney, one figure-8 hypertensive rat.

et al. 1992

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This study examines the relation between sympathetic activity and in vivo insulin-mediated glucose metabolism in a rat model of acquired hypertension. Two groups of conscious, unrestrained rats were studied in the postabsorptive state: sham-operated normotensive rats (n=10) and renal-wrapped hypertensive rats (n = 10). Mean arterial pressure was increased in the hypertensive compared with the normotensive group in the fed (184±9 versus 144±6 mm Hg; p<0.01) and in the fasting (147±8 versus 112±7 mm Hg; p<0.01) state. After a 24-hour fast, hepatic glucose production, plasma glucose, insulin, and norepinephrine concentrations were similar in the two groups. Blood pressure did not change in either group during the 3-milliunits/kg • min euglycemic insulin clamp study; however, plasma norepinephrine concentration rose significantly in hypertensive (207±24 versus 329±11 pg/ml;p<0.05) but not in normotensive rats (229±23 versus 267±27 pg/ml; p=NS). During the insulin clamp study, the hepatic glucose production was similar in the hypertensive (3.8±0.8 mg/kg • min) compared with the normotensive (4.0±0-3 mg/kg • min) rats. Insulin-mediated glucose uptake was significantly higher in hypertensive than in normotensive rats (33.0±0.7 versus 25.8±0.8;p<0.01). This increase was mostly due to a marked increase in skeletal muscle glycogen synthesis in the hypertensive versus the normotensive group (11.9±1.0 versus 6.9±0.8;/?<0.01), whereas the stimulation of whole body glycolysls (production of 3 H 2 O) was not significantly different in the two groups (14.7±0.8 versus 15.9±0.9 mg/kg • min in normotensive and hypertensive rats, respectively; p=NS). After euglycemic insulin infusion, plasma norepinephrine concentration increased in hypertensive but not in normotensive rats; however, the blood pressure did not change in either group. Peripheral insulin sensitivity is increased in rats with acquired sodium-sensitive hypertension. These results indicate that sodium-dependent hypertension is associated with enhanced response of the sympathetic nervous system to insulin and with increased insulin sensitivity. (Hypertension 1992^0:192-198) KEY WORDS • insulin • sodium • renovascular hypertension • sympathetic nervous system • hypertension, sodium-dependent R ecent metabolic and epidemiological observations demonstrate the association of essential hypertension and insulin resistance. 1 -10 Increased sympathoadrenal activity has been suggested to play a determinant role in the development and maintenance of high blood pressure in human essential hypertension and in several animal models of hypertension.11 -20 These findings have prompted speculation on the role of the sympathetic nervous system in the onset of insulin resistance.6 -8 ' 21 ' 22 Catecholamines, indeed, display potent metabolic effects.23 -29 Particularly, suppression of insulin secretion by catecholamines is mediated through a-adrenergic receptors, 25 whereas in human subjects, the direct effects of catecholamines on periph- eral and hepatic glucose metabolism appear to...

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Inhibitory Effect of Epinephrine on Insulin-stimulated Glucose Uptake by Rat Skeletal Muscle

Cited by 169 publications

References 36 publications

Induction of rat muscle insulin resistance by epinephrine is accompanied by increased interstitial glucose and lactate concentrations

Induction of rat muscle insulin resistance by epinephrine is accompanied by increased interstitial glucose and lactate concentrations

Effects of Adrenodemedullation on In Vivo Insulin-Stimulated Glucose Utilization in Relation to Glycolysis in Rat Peripheral Tissue.

Increased insulin sensitivity in the high sodium one-kidney, one figure-8 hypertensive rat.

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