Correction of chronic hyperglycemia with vanadate, but not with phlorizin, normalizes in vivo glycogen repletion and in vitro glycogen synthase activity in diabetic skeletal muscle.

Rossetti, Luciano; Lauglin, M R

doi:10.1172/jci114250

Cited by 117 publications

(104 citation statements)

References 43 publications

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“…At the end of all the in vivo studies, rats were anesthetized (pentobarbital 60 mg/kg body weight, intravenously); the abdomen was quickly opened, and the rectus abdominal muscle was freeze-clamped in situ with aluminum tongs precooled in liquid nitrogen (1,24). The time from injection of the anesthetic to freeze clamping of the muscle was approximately 30 s. All tissue samples were stored at Ϫ80°C for subsequent analysis.…”

Section: In Vivo Studiesmentioning

confidence: 99%

“…1B)-Euglycemic, hyperinsulinemic (18 milliunits/kg⅐min) clamp studies were performed for 3 h in combination with [3-3 H]glucose infusion as described previously (1,24,26). GlcN (750 mol/kg bolus, 30 mol/kg⅐min) was administered throughout the 3-h insulin clamp studies (n ϭ 5), while time control euglycemic, hyperinsulinemic clamp studies were performed with infusion of saline for 3 h in additional age-and weight-matched control rats (n ϭ 6).…”

Section: In Vivo Studiesmentioning

confidence: 99%

“…Muscle glycogen concentration was determined following digestion with amyloglucosidase as described previously (24). Muscle glycogen synthase activity was measured by a modification (24,26) of the method of Thomas et al (27) and is based on the measurement of the incorporation of radioactivity into glycogen from UDP-[U- 14 C]glucose.…”

Section: Glycogen Formation In Vivo and Glycogen Synthase Activitymentioning

confidence: 99%

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Discordant Effects of Glucosamine on Insulin-stimulated Glucose Metabolism and Phosphatidylinositol 3-Kinase Activity

Hawkins¹,

et al. 1999

Journal of Biological Chemistry

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The impact of increased GlcN availability on insulinstimulated p85/p110 phosphatidylinositol 3-kinase (PI3K) activity in skeletal muscle was examined in relation to GlcN-induced defects in peripheral insulin action. Primed continuous GlcN infusion (750 mol/kg bolus; 30 mol/kg⅐min) in conscious rats limited both maximal stimulation of muscle PI3K by acute insulin (I) (1 unit/kg) bolus (I ؉ GlcN ‫؍‬ 1.9-fold versus saline ‫؍‬ 3.3-fold above fasting levels; p < 0.01) and chronic activation of PI3K following 3-h euglycemic, hyperinsulinemic (18 milliunits/kg⅐min) clamp studies (I ؉ GlcN ‫؍‬ 1.2-fold versus saline ‫؍‬ 2.6-fold stimulation; p < 0.01). To determine the time course of GlcN-induced defects in insulin-stimulated PI3K activity and peripheral insulin action, GlcN was administered for 30, 60, 90, or 120 min during 2-h euglycemic, hyperinsulinemic clamp studies. Activation of muscle PI3K by insulin was attenuated following only 30 min of GlcN infusion (GlcN 30 min ‫؍‬ 1.5-fold versus saline ‫؍‬ 2.5-fold stimulation; p < 0.05). In contrast, the first impairment in insulin-mediated glucose uptake (Rd) developed following 110 min of GlcN infusion (110 min ‫؍‬ 39.9 ؎ 1.8 versus 30 min ‫؍‬ 42.8 ؎ 1.4 mg/kg⅐min, p < 0.05). However, the ability of insulin to stimulate phosphatidylinositol 3,4,5-trisphosphate production and to activate glycogen synthase in skeletal muscle was preserved following up to 180 min of GlcN infusion. Thus, increased GlcN availability induced (a) profound and early inhibition of proximal insulin signaling at the level of PI3K and (b) delayed effects on insulin-mediated glucose uptake, yet (c) complete sparing of insulin-mediated glycogen synthase activation. The pattern and time sequence of GlcN-induced defects suggest that the etiology of peripheral insulin resistance may be distinct from the rapid and marked impairment in insulin signaling.The hexosamine biosynthetic pathway in skeletal muscle serves a vital role in the production of the amino sugars that are utilized in multiple glycosylation pathways. Increased biosynthetic activity within the hexosamine pathway is associated with the development of insulin resistance (1-5). In fact, increasing the amount of flux into the GlcN pathway by various means has been shown to induce defects in insulin-stimulated glucose uptake (1, 2, 4 -6), GLUT4 translocation (3), and glycogen synthase activation (5,7,8).Entry into the hexosamine pathway involves the conversion of fructose 6-phosphate to glucosamine 6-phosphate via the rate-limiting enzyme glutamine fructose-6-P-amidotransferase (9). The principal end product of the pathway is UDP-GlcNAc (10), which modifies intracellular proteins by glycosylation. Thus, even modest perturbations of the amount of flux through the hexosamine pathway could have diverse effects on protein functions. The amount of flux into the pathway, estimated by the accumulation of UDP-GlcNAc in muscle, is strongly correlated with the degree of impairment in peripheral insulin action (5).The mechanism(s) of GlcN-induced defect...

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Section: In Vivo Studiesmentioning

confidence: 99%

Section: In Vivo Studiesmentioning

confidence: 99%

Section: Glycogen Formation In Vivo and Glycogen Synthase Activitymentioning

confidence: 99%

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Discordant Effects of Glucosamine on Insulin-stimulated Glucose Metabolism and Phosphatidylinositol 3-Kinase Activity

Hawkins¹,

et al. 1999

Journal of Biological Chemistry

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“…Под действием ортованадата повышается содержание и активность ферментов, участвующих в синтезе гликогена -гликогенсинтазы (КФ 2.4.1.11) и фосфорилазы (КФ 2.4.1.1) [61,62]. В скелетной мышце крыс со стрептозотоциновым диабетом ванадил оказывает похожие эффекты: ингибирует образование глюкозы в процессе глюконеогенеза, усиливает гликолиз [63] и синтез гликогена [64].…”

Section: таблица формулы соединений (продолжение)unclassified

The vanadium compounds: chemistry, synthesys, insulinomimetic properties

et al. 2014

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The review considers the biological role of vanadium, its participation in various processes in humans and other mammals, and the anti-diabetic effect of its compounds. Vanadium salts have persistent hypoglycemic and antihyperlipidemic effects and reduce the probability of secondary complications in animals with experimental diabetes. The review contains a detailed description of all major synthesized vanadium complexes having antidiabetic activity. Currently, vanadium complexes with organic ligands are more effective and safer than the inorganic salts. Despite the proven efficacy of these compounds as the anti-diabetic agents in animal models, only one organic complex of vanadium is currently under the second phase of clinical trials. All of the considered data suggest that vanadium compound are a new promising class of drugs in modern pharmacotherapy of diabetes.

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“…Because the basal muscle glycogen concentration was similar in all rats and the muscle mass in the rat represents 40% of the body weight, 146 it is possible to calculate the contribution of skeletal muscle glycogen synthesis to the whole body glucose uptake from the increment in glycogen concentration. 44 - 46 The difference in glucose incorporation into glycogen between normotensive and hypertensive rats can account for the majority of the increase in whole body glucose uptake observed in hypertensive animals. These results demonstrate an increased sensitivity to insulin of glucose uptake and muscle glycogen synthesis in a sodiumsensitive model of renal hypertension that is associated with increased sympathetic nervous system function.…”

Section: Sham Wrap Bmentioning

confidence: 99%

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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Correction of chronic hyperglycemia with vanadate, but not with phlorizin, normalizes in vivo glycogen repletion and in vitro glycogen synthase activity in diabetic skeletal muscle.

Cited by 117 publications

References 43 publications

Discordant Effects of Glucosamine on Insulin-stimulated Glucose Metabolism and Phosphatidylinositol 3-Kinase Activity

Discordant Effects of Glucosamine on Insulin-stimulated Glucose Metabolism and Phosphatidylinositol 3-Kinase Activity

The vanadium compounds: chemistry, synthesys, insulinomimetic properties

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

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