Physiological insulin action is opposed by beta-adrenergic mechanisms in dogs

1988 ◽  
Vol 255 (1) ◽  
pp. E33-E40 ◽  
Author(s):  
G. A. Werther ◽  
S. Joffe ◽  
R. Artal ◽  
M. A. Sperling
Keyword(s):  
Insulin Infusion ◽  
Glucose Production ◽  
Beta Blockade ◽  
Base Line ◽  
Adrenergic Blockade ◽  
Hormonal Changes ◽  
Beta Adrenergic ◽  
Adrenergic Mechanisms ◽  
Alpha Blockade

To investigate the possible role of adrenergic mechanisms in modulating glucose homeostasis during physiological insulin changes, we studied the effects of alpha-, beta-, or combined alpha- and beta-adrenergic blockade on glucose production (Ra) and utilization (Rd) via isotope ([3-(3)H]glucose) dilution during nonstressful, nonhypoglycemic conditions in response to physiological insulin changes in conscious dogs. Without adrenergic blockade, infusion of insulin at 0.275 mU.kg-1.min-1 (control) caused glucose to fall from 92 +/- 4 to 82 +/- 4 mg/dl over 30 min, because of transient fall in Ra from 2.8 +/- 0.4 to 2.3 +/- 0.3 mg.kg-1.min-1, which recovered to base line by 30 min. There was a later rise in Rd to 3.9 +/- 0.4 mg.kg-1.min-1 at 45 min, but no counter-regulatory hormonal changes (glucagon, cortisol, epinephrine, and norepinephrine) to account for these findings in glucose kinetics. alpha-Blockade alone led to an initial rise in base-line insulin and consequent fall in glucose, associated with a transient fall in Ra but no change in Rd; infusion of insulin led to a further small fall in glucose, with no change in Ra, but with a rise at 30 min in Rd similar to controls. beta-Blockade alone led to an initial fall in insulin and modest rise in glucose; insulin infusion led to a greater rate of fall in glucose than in controls (from 112 +/- 6 to 78 +/- 7 mg/dl over 30 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced beta-adrenergic-receptor responsiveness in hypoxic neonatal pulmonary circulation

1981 ◽  
Vol 240 (5) ◽  
pp. H697-H703 ◽  
Author(s):  
J. E. Lock ◽  
P. M. Olley ◽  
F. Coceani
Keyword(s):  
Pulmonary Circulation ◽  
Beta Blockade ◽  
Base Line ◽  
Pulmonary Resistance ◽  
Beta Adrenergic ◽  
Beta Receptor ◽  
Adrenergic Activity ◽  
Alpha Blockade ◽  
Alveolar Hypoxia ◽  
Constrictor Response

The influence of alveolar hypoxia on pulmonary vascular adrenergic receptors was studied in conscious newborn lambs. In control animals, pulmonary vessels were directly constricted by epinephrine and norepinephrine, but were unaffected by isoproterenol. Pulmonary resistance (PVR) was also unaffected by propranolol, thus implying minimal beta-receptor activity under normoxic conditions. Hypoxia raised PVR but also modified the pulmonary vascular responses to catecholamines: isoproterenol became a dilator, whereas the constrictor effects of epinephrine and norepinephrine were abolished. Although beta-blockade did not alter base-line PVR, propranolol increased the constrictor response to hypoxia, implying that hypoxia increases beta-adrenergic activity or reactivity in the pulmonary circulation. Consistent with this hypothesis are the following: 1) in alpha-blocked lambs, epinephrine was without local effects during normoxia, but caused vasodilation during hypoxia; 2) the absent constrictor response to epinephrine during hypoxia is fully restored by propranolol; and 3) although alpha-blockade blunts the hypoxic constrictor response, the full response is restored when beta-blockade is added. These results indicate that the hypoxic constrictor response is partially opposed by increased beta-mediated vasodilation. These enhanced beta-receptor effects are due, at least in part, to increased beta-receptor reactivity of unknown mechanism.

Role of beta-adrenergic mechanisms during exercise in poorly controlled diabetes

1985 ◽  
Vol 59 (4) ◽  
pp. 1282-1289 ◽  
Author(s):  
D. H. Wasserman ◽  
H. L. Lickley ◽  
M. Vranic
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Beta Blockade ◽  
Metabolic Clearance ◽  
Beta Adrenergic ◽  
Hepatic Glucose ◽  
Elevated Glucose ◽  
Lactate Levels ◽  
Response To Exercise

To examine the beta-adrenergic effects of the catecholamines in poorly controlled diabetes, we have studied insulin-deprived alloxan-diabetic (A-D) dogs during 90 min of moderate exercise (100 m/min, 10–12 degrees) alone (C) or with propranolol (5 micrograms . kg-1 . min-1) (P) or combined P and somatostatin infusion (0.5 microgram . kg-1 . min-1) (P + St). In P, in contrast to C, immunoreactive glucagon (IRG) rose only after 50 min of exercise. However, hepatic glucose production (Ra) rose normally. In P + St, IRG fell 50% below basal, and the Ra response to exercise was abolished. Interestingly, in P and P + St, glucose metabolic clearance rate (MCR) rose by 400% above the inadequate MCR response to exercise in C, despite 30% lower insulin levels. Compared with C, free fatty acids (FFA) and lactate were sharply reduced during P and P + St. Plasma glucose (G) did not change in C, but due to elevated glucose uptake, G fell over 120 mg/dl in P, and due to diminished Ra, G fell 170 mg/dl in P + St. Norepinephrine was similar in all groups. Epinephrine and cortisol were higher in P + St by 90 min of exercise, perhaps as a result of hypoglycemia. In summary, during exercise in poorly controlled A-D dogs, beta-blockade does not appear to affect Ra; beta-blockade leads to diminished mobilization of extrahepatic substrate as evidenced by reduced FFA and lactate levels; beta-blockade increases MCR to levels seen in normal dogs during exercise alone.

Glucoregulation during insulin and glucagon deficiency: role of catecholamines

1982 ◽  
Vol 243 (3) ◽  
pp. E225-E233
Author(s):  
D. J. Koerker ◽  
J. B. Halter
Keyword(s):  
Plasma Catecholamines ◽  
Glucose Production ◽  
Glucagon Secretion ◽  
Hormone Deficiency ◽  
Beta Blockade ◽  
Adrenergic Blockade ◽  
Beta Adrenergic ◽  
Adrenergic Mechanism ◽  
Islet Hormone ◽  
Alpha Receptors

Glucose production decreases markedly following acute reduction in insulin and glucagon secretion (induced by somatostatin). After about an hour, however, glucose production is restored nearly to basal rates. To study the mechanism by which this occurs, islet hormone deficiency was superimposed on beta-adrenergic blockade. It was found that the hypoglycemia that accompanies insulin and glucagon deficiency is an adequate stimulus for catecholamine secretion. During combined hormone deficiency and beta-blockade, glucose production fell and remained very low for 2-3 h. This resulted in a profound hypoglycemia (glucose less than 30 mg/dl). We conclude from these studies that restoration of glucose production during sustained insulin and glucagon deficiency is not attributable to a) onset of insulin deficiency because insulin is equally depressed in both experimental settings, b) glucose autoregulation even though adequate substrate is available, or c) an alpha-adrenergic mechanism because plasma catecholamines were very high and alpha-receptors were not blocked. Rather, the glucose counterregulation during insulin and glucagon deficiency must be heavily dependent on a beta-adrenergic mechanism.

Role of gluconeogenesis in sustaining glucose production during hypoglycemia caused by continuous insulin infusion in conscious dogs

Diabetes ◽  
1988 ◽  
Vol 37 (6) ◽  
pp. 749-759 ◽  
Author(s):  
R. T. Frizzell ◽  
G. K. Hendrick ◽  
D. W. Biggers ◽  
D. B. Lacy ◽  
D. P. Donahue ◽  
...  
Keyword(s):  
Insulin Infusion ◽  
Glucose Production ◽  
Conscious Dogs ◽  
Continuous Insulin Infusion

Effect of beta-adrenergic blockade on lactate turnover in exercising dogs

1984 ◽  
Vol 57 (6) ◽  
pp. 1754-1759 ◽  
Author(s):  
B. Issekutz
Keyword(s):  
Plasma Glucose ◽  
Lactate Production ◽  
Hormonal Control ◽  
Glucose Turnover ◽  
Beta Blockade ◽  
Adrenergic Blockade ◽  
Metabolic Clearance ◽  
Beta Adrenergic ◽  
Indwelling Catheters ◽  
Lactate Turnover

Dogs with indwelling catheters in the jugular vein and in the carotid artery ran on the treadmill (slope: 15%, speed: 133 m/min). Lactate turnover and glucose turnover were measured using [U-14C]lactate and [3-3H]glucose as tracers, according to the primed constant-rate infusion method. In addition, the participation of plasma glucose in lactate production (Ra-L) was measured with [U-14C]glucose. Propranolol was given either (A) before exercise (250 micrograms/kg, iv) or (B) in form of a primed infusion administered to the dog running at a steady rate. Measurements of plasma propranolol concentration showed that in type A experiments plasma propranolol fell in 45 min below the lower limit of the complete beta-blockade. In the first 15 min of work Ra-L rose rapidly; then it fell below that of the control (exercise) values. During steady exercise, the elevated Ra-L was decreased by propranolol infusion close to resting values. beta-Blockade doubled the response of glucose production, utilization, and metabolic clearance rate to exercise. In exercising dogs approximately 40-50% of Ra-L arises from plasma glucose. This value was increased by the blockade to 85-90%. It is concluded that glycogenolysis in the working muscle has a dual control: 1) an intracellular control operating at the beginning of exercise, and 2) a hormonal control involving epinephrine and the beta-adrenergic receptors.

Beta-adrenergic blockade alters whole-body leucine metabolism in humans

1989 ◽  
Vol 67 (1) ◽  
pp. 221-225 ◽  
Author(s):  
L. S. Lamont ◽  
D. G. Patel ◽  
S. C. Kalhan
Keyword(s):  
Skeletal Muscle ◽  
Blocking Agent ◽  
Whole Body ◽  
Beta Blockade ◽  
Adrenergic System ◽  
Adrenergic Blockade ◽  
Beta Adrenergic ◽  
Leucine Metabolism ◽  
Leucine Oxidation ◽  
Tracer Dilution

This study examined the effects of a nonselective beta-blocking agent on whole-body leucine metabolism in humans. Five normal, healthy subjects (4 male, 1 female) underwent a 6-h primed, constant-rate infusion of L-[1–13C]leucine after 5 days of twice daily oral use of 80 mg propranolol and a placebo. Leucine turnover was determined by tracer dilution and leucine oxidation by 13C enrichment of the expired CO2. Propranolol decreased the total daily energy expenditure from 1,945 +/- 177.5 to 1,619 +/- 92.5 kcal/day (P less than 0.05). A fasting associated decrease in blood glucose and an attenuated rise in free fatty acids and ketones were observed during beta-blockade. Propranolol also increased plasma leucine concentrations (73.1 +/- 8.7 to 103.4 +/- 7.3 mumol/l; P less than 0.05) and leucine oxidation (13.2 +/- 1.2 to 17.1 +/- 1.3 mumol.kg-1.h-1; P less than 0.05), although leucine turnover was not significantly altered (100.5 +/- 7.3 vs. 126.0 +/- 12.3 mumol.kg-1.h-1). In addition, the urinary urea nitrogen-to-creatinine ratio was greater during propranolol administration (0.24 +/- 0.04 vs. 0.34 +/- 0.02 mol/g; P less than 0.05). These data suggest that the beta-adrenergic system plays a role in the modulation of whole-body leucine metabolism in humans. Whether these changes are the result of a direct effect on skeletal muscle or an indirect effect mediated by altering the fuel supply to skeletal muscle cannot be discriminated by the present study.

scholarly journals The Role of Cardioselective versus Non-Cardioselective Beta-Adrenergic Blockade in the Acute Phase of Takotsubo Cardiomyopathy

2019 ◽  
Vol 25 (8) ◽  
pp. S28
Author(s):  
Muhhammad Saad ◽  
Hitesh Gurjar ◽  
Miguel Rodriguez ◽  
Pranav Sharma ◽  
Swathi Roy ◽  
...  
Keyword(s):  
Acute Phase ◽  
Takotsubo Cardiomyopathy ◽  
Adrenergic Blockade ◽  
Beta Adrenergic

Effects of beta-adrenergic agents in lungs of normal and air-embolized awake sheep

1988 ◽  
Vol 64 (6) ◽  
pp. 2647-2652 ◽  
Author(s):  
M. R. Bonsignore ◽  
E. H. Jerome ◽  
P. L. Culver ◽  
P. M. Dodek ◽  
N. C. Staub
Keyword(s):  
Air Embolism ◽  
Lymph Flow ◽  
Beta Agonist ◽  
Beta Blockade ◽  
Base Line ◽  
Pulmonary Hemodynamics ◽  
Beta Adrenergic ◽  
Adrenergic Agents ◽  
Venous Air Embolism ◽  
Lung Lymph

It is unclear whether beta-adrenergic agonists or antagonists affect lung liquid and protein exchange by changing pulmonary hemodynamics or microvascular leakiness. In 23 unanesthetized, instrumented sheep with long-term lung lymph fistulas, we assessed the effect of the beta-agonist terbutaline or the beta-antagonists propranolol, nadolol, and atenolol, all infused intravenously, on lung lymph flow under base-line conditions and during the acute lung injury caused by 4 h of venous air embolism. Under base-line conditions, neither beta-stimulation nor blockade had any effect. During air embolism, terbutaline decreased pulmonary vascular resistance and lymph flow by 25%. Propranolol and nadolol (non-selective beta 1,beta 2-antagonists) but not atenolol (selective beta 1-antagonist) also decreased lymph flow by 22% on average. We favor the more conservative (hemodynamic) over the more liberal (altered permeability) explanation for our results. First, beta-stimulation clearly caused vasodilation, which lowered the pulmonary microvascular pressure at the site of injury. beta-blockade caused changes similar to alpha-stimulation (J. Appl. Physiol. 62: 2147–2153, 1987). We therefore interpret the beta-blockade as unmasking pulmonary arterial alpha-receptors stimulated by the air-embolism injury, thus allowing vasoconstriction upstream to the site of injury. We do not believe the explanation of the beta-agent effects requires any modulation of lung microvascular leakiness by beta-adrenergic agents.

Adrenoceptor control of lung fluid and protein exchange

1981 ◽  
Vol 51 (1) ◽  
pp. 68-72 ◽  
Author(s):  
T. S. Hakim ◽  
F. L. Minnear ◽  
H. van der Zee ◽  
P. S. Barie ◽  
A. B. Malik
Keyword(s):  
Steady State ◽  
Surface Area ◽  
Left Atrial ◽  
Endothelial Permeability ◽  
Base Line ◽  
Adrenergic Blockade ◽  
Beta Adrenergic ◽  
Lung Fluid ◽  
Vascular Surface ◽  
Protein Exchange

We studied the effects of alpha- and beta-adrenergic antagonists on lung fluid and protein exchange in anesthetized sheep. alpha-Adrenergic blockade with 2 mg/kg phentolamine caused a transient and small decrease in lung lymph flow (Qlym), which was associated with a decrease in mean pulmonary arterial pressure (Ppa); but the steady-state Qlym and mean left atrial pressure were not different from base-line values. In contrast, beta-adrenergic blockade with propranolol (2 mg/kg) caused an increase in Qlym from a base-line value of 7.7 +/- 2.2 ml/h to a steady-state value of 10.6 +/-2.3 ml/h within 2 h (P less than 0.05), which was not associated with a change in Ppa. The increase in Qlym persisted for the 4-h duration of the study. The 39% increase in Qlym after propranolol was associated with a 50% increase in transvascular protein clearance (CL), whereas in control animals the 100% increase in Qlym after left atrial hypertension was associated with only a 36% increase in CL, indicating increased transvascular transport of proteins after propranolol. The transient decrease in Qlym after phentolamine may be due to the short-lasting decreased in pulmonary microvascular pressure and vascular surface area. However, the long-lasting increases in Qlym and CL after propranolol may be due to an increase in vascular surface area and to an increase in endothelial permeability of proteins. The results suggests that beta-adrenergic receptors regulate the transendothelial transport of fluid and proteins.

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