Regulation of gluconeogenesis by norepinephrine, vasopressin, and angiotensin II: A comparative study in the absence and presence of extracellular Ca2+

Kneer, Nancy; Lardy, Henry A.

doi:10.1016/0003-9861(83)90022-x

Cited by 47 publications

(29 citation statements)

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“…18 Previous reports of the beneficial effects of ACEIs on insulin sensitivity and glucose metabolism have generated much speculation regarding potential mechanisms, including inhibition of angiotensin II formation, 19,20 inhibition of BK degradation, 2 vasodilatation of insulin-sensitive tissues, or reduction in circulating catecholamines. 5,19,20 There is, however, increasing experimental evidence to suggest that the BK-NO pathway plays a major role, 2 partly independent of changes in muscle blood flow. In experimental models of diabetes, exogenous BK and ACEI were found to enhance insulin sensitivity and increase glucose uptake by both skeletal 3,4 and cardiac muscle.…”

Section: Discussionmentioning

confidence: 99%

“…The role of BK in mediating the insulin-sensitizing effect of OMA on myocardium might not be as great as its role in skeletal muscles and adipose tissues. Reduction of angiotensin II levels by OMA could have directly affected the myocardium (OMA ϩ inhibitors induced the same insulinstimulated glucose uptake as losartan), because angiotensin II has both glycogenolytic and gluconeogenic properties 19,20 and may play an important role in myocardial glycogen-rich tissue. 28 In addition, the NO effect in myocardium is still controversial, with some reports showing that NO actually decreases myocardial glucose uptake.…”

Section: Discussionmentioning

confidence: 99%

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Vasopeptidase Inhibitor Omapatrilat Induces Profound Insulin Sensitization and Increases Myocardial Glucose Uptake in Zucker Fatty Rats

et al. 2003

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Background-ACE inhibitors (ACEIs) improve insulin resistance and prevent type 2 diabetes, possibly mediated by inhibition of bradykinin (BK) degradation. The vasopeptidase inhibitor omapatrilat (OMA) raises BK to a greater extent than ACEIs by dual enzyme inhibition, whereas its insulin-sensitizing effects and mechanisms have not been investigated. Methods and Results-We compared the insulin-sensitizing effects of OMA, ramipril (an ACEI), losartan (an angiotensin II type 1 receptor blocker), and placebo by 2-step euglycemic hyperinsulinemic clamp in insulin-resistant Zucker fatty rats (nϭ6 to 7 in each group). OMA resulted in a lower rate of endogenous glucose production than placebo at baseline (35Ϯ5 versus 54Ϯ4 mmol · kg Ϫ1 · min Ϫ1 , PϽ0.01), greater suppression of endogenous glucose production by low-dose insulin (73Ϯ11% versus 27Ϯ18%, PϽ0.05), and greater glucose disposal at high-dose insulin (135Ϯ5 versus 92Ϯ4 mmol · kg Ϫ1 · min

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vasopeptidase Inhibitor Omapatrilat Induces Profound Insulin Sensitization and Increases Myocardial Glucose Uptake in Zucker Fatty Rats

et al. 2003

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“…These effects have been observed as calcium-dependent stimulation of glucose production from sorbitol [32], glycerol [16,32,331 and xylitol [34]. These compounds are reduced with respect to glucose and require shuttle activity for their metabolism.…”

Section: Discussionmentioning

confidence: 99%

Calcium and 2‐oxoglutarate‐mediated control of aspartate formation by rat heart mitochondria

Scaduto

1994

European Journal of Biochemistry

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Studies of the influence of calcium on the metabolism of cardiac mitochondria have indicated that calcium activates key enzymes involved in the citric acid cycle. Calcium-mediated activation of one of these enzymes, 2-oxoglutarate dehydrogenase, has been shown to cause a marked decrease in the steady-state concentration of 2-oxoglutarate in both heart and liver mitochondria. In liver, 2-oxoglutarate is a potent inhibitor of oxalacetate transamination to aspartate and activation of this enzyme by calcium-mobilizing hormones leads to a stimulation of aspartate formation and gluconeogenesis. Since mitochondrial aspartate formation is a key step in the malate/aspartate shuttle, we investigated the control of aspartate formation by cardiac mitochondria. In mitochondria incubated with glutamate and malate, activation of 2-oxoglutarate dehydrogenase by calcium led to an inhibition of aspartate formation. However, calcium caused a stimulation of aspartate production when incubations were supplemented with pyruvate as an additional substrate. Estimates of the mitochondrial redox potential (NADWNAD') indicated that both calcium and pymvate increased the redox potential. The observed influence of calcium on aspartate formation was found to be due to a balance between its inhibitory effect, caused by an increased redox potential, and its stimulatory effect, caused by a decreased 2-oxoglutarate concentration. Under conditions in which the redox component was held constant, a kinetic analysis indicated that the apparent K, for 2-oxoglutarate inhibition of aspartate formation is 0.2 mM. The data suggest that activation of cardiac 2-oxoglutarate dehydrogenase by calcium could lead to stimulation of the mitochondrial oxidation of cytosolic NADH via the malate/aspartate cycle.It is generally accepted that the rate of energy utilization within the cell by various ATPases is well matched to the rate of ATP production such that the cellular concentration of ATP does not vary widely despite physiological fluctuations in energy expenditure. However, the manner by which the cell achieves this tight coupling remains a topic of active study. In now classical studies of isolated mitochondria, the control of mitochondrial respiration was viewed as being regulated solely through either ADP availability [l] or the ATP/ ADP ratio [2, 31. More recently, however, these conclusions have been brought into question since these variables have been found not to change appreciably over a wide range of oxygen consumption in studies of the intact heart using more noninvasive techniques [4, 51. Reviews of this topic have appeared [6 -81.It is now well established that mitochondria contain three dehydrogenases that are sensitive to changes in matrix calcium [9]. These enzymes are pyruvate dehydrogenase, isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase. All of these enzymes are displaced far from thermodynamic equilibrium and hence modulation of their activity by calcium can have an important influence on citric acid cycle flux [lo]. In previous...

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“…Several in vitro hepatocyte studies have shown that angiotensin II stimulates glycogen phosphorylase activity (4)(5)(6) and gluconeogenesis (7)(8)(9)(10). Recently, we have shown that RAS involvement in blood glucose regulation is of physiological significance, with angiotensin II producing a dose-dependent hyperglycemic response (1).…”

mentioning

confidence: 99%

The hyperglycemia induced by angiotensin II in rats is mediated by AT1 receptors

Machado

Marubayashi

Reis

et al. 1998

Braz J Med Biol Res

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We have shown that the renin-angiotensin system (RAS) is involved in glucose homeostasis during acute hemorrhage. Since almost all of the physiological actions described for angiotensin II were mediated by AT 1 receptors, the present experiments were designed to determine the participation of AT 1 receptors in the hyperglycemic action of angiotensin II in freely moving rats. The animals were divided into two experimental groups: 1) animals submitted to intravenous administration of angiotensin II (0.96 nmol/100 g body weight) which caused a rapid increase in plasma glucose reaching the highest values at 5 min after the injection (33% of the initial values, P<0.01), and 2) animals submitted to intravenous administration of DuP-753 (losartan), a nonpeptide antagonist of angiotensin II with AT 1 -receptor type specificity (1.63 µmol/100 g body weight as a bolus, iv, plus a 30-min infusion of 0.018 µmol 100 g body weight -1 min -1 before the injection of angiotensin II), which completely blocked the hyperglycemic response to angiotensin II (P<0.01). This inhibitory effect on glycemia was already demonstrable 5 min (8.9 ± 0.28 mM, angiotensin II, N = 9 vs 6.4 ± 0.22 mM, losartan plus angiotensin II, N = 11) after angiotensin II injection and persisted throughout the 30-min experiment. Controls were treated with the same volume of saline solution (0.15 M NaCl). These data demonstrate that the angiotensin II receptors involved in the direct and indirect hyperglycemic actions of angiotensin II are mainly of the AT 1 -type. Key wordsIn addition to affecting fluid volume, electrolytes and hemodynamic states, the renin-angiotensin system (RAS) is also involved in the regulation of metabolic and endocrine function, especially blood glucose homeostasis (1-3). Several in vitro hepatocyte studies have shown that angiotensin II stimulates glycogen phosphorylase activity (4-6) and gluconeogenesis (7-10). Recently, we have shown that RAS involvement in blood glucose regulation is of physiological significance, with angiotensin II producing a dose-dependent hyperglycemic response (1). In contrast, intravenous infusion of an angiotensin II peptide-analog antagonist, [1-sar,8-thr]-angiotensin II (sarthran), had an

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Regulation of gluconeogenesis by norepinephrine, vasopressin, and angiotensin II: A comparative study in the absence and presence of extracellular Ca2+

Cited by 47 publications

References 53 publications

Vasopeptidase Inhibitor Omapatrilat Induces Profound Insulin Sensitization and Increases Myocardial Glucose Uptake in Zucker Fatty Rats

Vasopeptidase Inhibitor Omapatrilat Induces Profound Insulin Sensitization and Increases Myocardial Glucose Uptake in Zucker Fatty Rats

Calcium and 2‐oxoglutarate‐mediated control of aspartate formation by rat heart mitochondria

The hyperglycemia induced by angiotensin II in rats is mediated by AT1 receptors

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