Glucose Inhibition of Epinephrine Stimulation of Hepatic Gluconeogenesis by Blockade of the α-Receptor Function

Kneer, Nancy; Bosch, A.L.; Clark, Michael G.; Lardy, Henry A.

doi:10.1073/pnas.71.11.4523

Cited by 72 publications

(18 citation statements)

References 20 publications

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“…Although this is the first demonstration of an acute increase in plasma norepinehprine (as opposed to epinephrine) during insulin-induced hypoglycemia (58), other investigators using 2-deoxyglucose-induced glucopenia in man have also emphasized the importance of the axonal release of norepinephrine for glucose homeostasis (59,60). Studies in vivo as well as in vitro have shown that both catecholamines activate glycogenolysis and increase the rate of gluconeogenesis from threecarbon intermediates such as alanine (2,3,12,61,62).…”

Section: Discussionmentioning

confidence: 99%

“…Many of these hormones are thought to antagonize the hypoglycemic action of insulin, by modulating either glucose production or glucose utilization or both. Catecholamines (1)(2)(3), glucagon (4)(5)(6)(7)(8)(9), and cortisol (10,11) increase the rate of hepatic gluconeogenesis from three-carbon precursors, such as lactate and alanine. Catecholamines and glucagon also accelerate hepatic glycogenolysis (12,13).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man.

Garber¹,

Cryer²,

Santiago³

et al. 1976

J. Clin. Invest.

362

135

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A B S T R A C T Sequential determinations of glucose outflow and inflow, and rates of gluconeogenesis from alanine, before, during and after insulin-induced hypoglycemia were obtained in relation to alterations in circulating epinephrine, norepinephrine, glucagon, cortisol, and growth hormone in six normal subjects. Insulin decreased the mean (+SEM) plasma glucose from 89+3 to 39+2 mg/dl 25 min after injection, but this decline ceased despite serum insulin levels of 153±22 gtU/ml.Before insulin, glucose inflow and outflow were constant, averaging 125.3±7.1 mg/kg per h. 15 min after insulin, mean glucose outflow increased threefold, but then decreased at 25 min, reaching a rate 15% less than the preinsulin rate. Glucose inflow decreased 80% 15 min after insulin, but increased at 25 min, reaching a maximum of twice the basal rate. Gluconeogenesis from alanine decreased 68% 15 min after insulin, but returned to preinsulin rates at 25 min, and remained constant for the next 25 min, after which it increased linearly. A fourfold increase in mean plasma epinephrine was found 20 min after insulin, with maximal levels 50 times basal. Plasma norepinephrine concentrations first increased significantly at 25 min after insulin, whereas significantly increased levels of cortisol and glucagon occurred at 30 min, and growth hormone at 40 min after insulin.Thus, insulin-induced hypoglycemia in man results from both a decrease in glucose production and an increase in glucose utilization. Accelerated glycogenolysis

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man.

Garber¹,

Cryer²,

Santiago³

et al. 1976

J. Clin. Invest.

362

135

View full text Add to dashboard Cite

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“…In contrast, stimulation of hepatic gluconeogenesis by a-adrenergic agonists is accompanied by changes in membrane permeability and resultant alterations in cellular contents of several ionic species (3,4) but proceeds, under some circumstances at least, without alterations in cyclic nucleotide levels (5)(6)(7). Because of its central role in regulation of cellular function, considerable attention has focused upon the possible involvement of changes in cellular Ca2+ in the mechanism of action of the a-adrenergic hormones.…”

mentioning

confidence: 99%

Norepinephrine, vasopressin, glucagon, and A23187 induce efflux of calcium from an exchangeable pool in isolated rat hepatocytes

Chen

Babcock

Lardy

1978

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

170

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Isolated rat hepatocytes do not actively accumulate Ca2+ during prolonged incubation in vitro; however, these cells do exhibit a limited exchange of intracellular with extracellular Ca2+. The exchangeable pool represents about 2 nmol of CaS+ per mg of protein. In medium containing either a low (20 MM) or high (1 mM) concentration of Ca2+, the divalent cation ionophore, A23187 (at concentrations of 0.03-0.1 nmol/ mg of protein), causes release of 42Cad+ from this exchangeable pool but does not allow net influx of extracellular CaZ+ detectable by the use of a Ca2+-sensitive electrode. Like A23187, the hormones norepinephrine, vasopressin, and glucagon (at concentrations that stimulate gluconeogenesis) each induces a similar net efflux of Ca2+. Treatment with one hormone decreases the subsequent reponse to the others, whereas treatment with A23187 abolishes the hormonal effects upon both Ca2. release and gluconeogenesis. The action of norepinephrine, but not of glucagon, upon CaO+ efflux is prevented by the a-adrenergic antagonist, phenoxybenzamine. The action of norepinephrine is not prevented by the ,B-adrenergic antagonist, propranolol Together these results indicate that the release of Ca2+ from a common pool of exchangeable Ca2+ is important to the action of a variety of hormones on hepatocytes. This Ca2+ pool in the isolated hepatocyte is characterized as being similar in size and having exchange kinetics that are com arable to those reported for the major intracellular pool of Ca + in the intact liver. The possibility that this pool is intramitochondrial calcium is discussed.The effects of glucagon upon gluconeogenesis in intact, perfused liver are mediated through alterations in cyclic nucleotide levels (1,2 Zahlten and Stratman (11). Routinely, cells were suspended at 6.5 X 106 cells per ml in Krebs-Henseleit bicarbonate medium containing 1.5% bovine serum albumin, 10 mM Na lactate, and 1 mM Na pyruvate without added calcium (the free calcium in the cell suspension was estimated at 15-30 gM). Cell suspensions (1.0 or 2.5 ml) were incubated in plastic scintillation vials at 370 in a Dubnoff shaker with agitation (110 cycle/min) under 95% 02/5% CO2.45Ca2+ Exchange Studies. After 40 min of equilibration, 10 gCi of 45Ca2+ was added to each 1.0 ml of cell suspension. Subsequently 20-,ul aliquots were removed for determination of isotopic Ca uptake. Each aliquot was layered on the top of 0.35 ml of 7% bovine serum albumin in 5 mM CaCl2/150 mM NaCl all contained in a 0.45-ml polyethylene centrifuge tube (no. 47/7, Sarstedt Co., Princeton, NJ). The tubes were then centrifuged for 15 sec at 2000 X g. The tips containing the cell pellet were cut off and their contents were flushed into scintillation vials by injecting 0.5 ml of 1% sodium dodecyl sulfate solution. The cells were solubilized with 5 ml of Aquasol and the associated radioactivity was determined.Ca2+ Electrode Studies. Cell suspensions of 2.5 ml were prepared as described above with each vial containing a Ca2+-sensitive and a reference electrod...

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“…Hypoglycaemia increases the circulating levels of several hormones, some of which, CA (Kneer, Bosch, Clark & Lardy, 1974), glucagon (Clark, Kneer, Bosch & Lardy, 1974) and cortisol (Exton, 1972), directly Figure 4 Effect of anti-angiotensin I antibodies on catecholamine release from cat adrenal medulla in response to hypoglycaemia: (-) control cats injected wiith insulin (10 u/kg; n = 9); (0) experimental group, cats administered insulin (10 u/kg; n = 4) and angiotensin I antibodies; the period of angiotensin I antibodies (Ab) infusion (0.1 ml kg-' min-') is indicated; I I Indicates time of insulin injection. *P < 0.05; **P < 0.02; ***P < 0.001.…”

Section: Discussionmentioning

confidence: 99%

Renin‐angiotensin Mediation of Adrenal Catecholamine Secretion Induced by Hypoglycaemia in the Cat

Bumpus

Feuerstein²,

Gutman³

et al. 1980

British J Pharmacology

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The mechanism involved in catecholamine (CA) release from the cat adrenal gland in response to insulin hypoglycaemia was studied. In intact cats, hypoglycaemia induced an 11 fold increase in adrenomedullary CA secretion. Acute bilateral nephrectomy nearly abolished the increased CA release from the adrenal gland during hypoglycaemia. Infusion of Sar1‐Ileu8‐Angiotensin II (AII), a competitive AII antagonist, suppressed the adrenomedullary response to the insulin‐induced hypoglycaemia. After termination of the antagonist infusion, CA secretion from the adrenal medulla increased rapidly, reaching the same level as in insulin‐treated cats. Infusion of rabbit anti‐angiotensin I antibodies suppressed CA release from the adrenal gland of hypoglycaemic cats. This effect was more prolonged than that of Sar1‐Ileu8‐AII. These results indicate that CA release from the adrenal medulla of the cat in response to insulin‐induced hypoglycaemia, is mediated through the renal reninangiotensin system. Since hypoglycaemia causes sympathetic stimulation through a central mechanism, angiotensin may act through the central nervous system.

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Glucose Inhibition of Epinephrine Stimulation of Hepatic Gluconeogenesis by Blockade of the α-Receptor Function

Cited by 72 publications

References 20 publications

The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man.

The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man.

Norepinephrine, vasopressin, glucagon, and A23187 induce efflux of calcium from an exchangeable pool in isolated rat hepatocytes

Renin‐angiotensin Mediation of Adrenal Catecholamine Secretion Induced by Hypoglycaemia in the Cat

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