Effects of adrenergic blockade on glucose kinetics in septic and burned guinea pigs

1981 ◽  
Vol 241 (3) ◽  
pp. R222-R227
Author(s):  
M. J. Durkot ◽  
R. R. Wolfe
Keyword(s):  
Guinea Pigs ◽  
Glucose Production ◽  
Constant Infusion ◽  
Adrenergic Blockade ◽  
Glucose Kinetics ◽  
Counterregulatory Hormones ◽  
Beta Adrenergic ◽  
Glucoregulatory Hormones ◽  
Adrenergic Blocker ◽  
Septic Group

We have used the primed-constant infusion of [6-3H]glucose to study the effects of phentolamine, an alpha-adrenergic blocker, and propranolol, a beta-adrenergic blocker, on glucose production and clearance in gastrostomy-fed control, septic (repeated sub-Q Escherichia coli injections), and burned (25-30% BSA) guinea pigs. Hypermetabolism and elevated glucoregulatory hormones were evident in both traumatized models, whereas their glucose kinetic response was different. Basal glucose production and clearance were elevated in the burned group and were depressed in the septic group when compared to control values. Propranolol caused a further increase in glucose production and clearance in the burned group, whereas it depressed glucose production and clearance to an even greater extent in the septic group. Phentolamine also produced an increase in glucose production and clearance in the burned group. In the septic group, phentolamine had no significant effect on glucose production, but clearance was significantly elevated. Thus, although alpha- or beta-adrenergic blockade normalized metabolic rate in both groups with respect to control animals, glucose kinetics remained different despite similar changes in counterregulatory hormones.

Beta-adrenergic contribution to glucagon-induced glucose production and insulin secretion in uremia

1986 ◽  
Vol 251 (3) ◽  
pp. E322-E327
Author(s):  
P. Baylor ◽  
S. Shilo ◽  
J. Zonszein ◽  
H. Shamoon
Keyword(s):  
Plasma Insulin ◽  
Insulin Response ◽  
Glucose Production ◽  
Adrenergic Blockade ◽  
Glucose Kinetics ◽  
Beta Adrenergic ◽  
Adrenergic Regulation ◽  
Insulin Secretory Response ◽  
Plasma Insulin Response ◽  
Normal Controls

Spontaneous or propranolol-induced hypoglycemia can occur in uremic humans. We studied glucose kinetics (using [3-3H]glucose) in five uremic humans 24 h after hemodialysis and in seven normal controls. The effect of glucagon infusion at rates of 3, 6, 12, and 18 ng X kg-1 X min-1 at 60-min intervals was compared with either saline or beta-adrenergic blockade (propranolol infusion). In uremics, plasma glucose increased by 20-25% and by 40-50% at the 3 and 6 ng X kg-1 X min-1 glucagon doses, respectively, with no further increases at higher infusion rates. Glucose production increased transiently and in tandem with glucose uptake at each glucagon increment (P less than 0.0001). During beta-adrenergic blockade, the effect of glucagon in stimulating glucose production was blunted by 14-24% at the 6-18 ng X kg-1 X min-1 doses (P less than 0.05). During saline infusion, plasma insulin concentrations increased progressively to peak levels fourfold above basal at the 18 ng X kg-1 X min-1 dose. This increase in plasma insulin was virtually abolished by concomitant beta-adrenergic blockade (P = 0.0002). In contrast to uremic subjects, normal controls exhibited lesser degrees of hyperglycemia and hyperinsulinemia at all glucagon infusion rates. Propranolol infusion had no effect on the increments in glucose production and uptake nor on the plasma insulin response. These results suggest that in uremic humans propranolol independently reduces the hepatic response to glucagon and the insulin secretory response to hyperglycemia and/or hyperglucagonemia. These observations provide a possible mechanism for the adrenergic regulation of glucose homeostasis in uremia.

Inhibitory effect of plasma free fatty acids on glucose production in the conscious dog

1984 ◽  
Vol 246 (2) ◽  
pp. E181-E186
Author(s):  
R. R. Wolfe ◽  
J. H. Shaw
Keyword(s):  
Glucose Production ◽  
Plasma Free Fatty Acid ◽  
Inhibitory Effect ◽  
Hormonal Control ◽  
Constant Infusion ◽  
Adrenergic Blockade ◽  
Beta Adrenergic ◽  
Adrenergic Activity ◽  
Plasma Ffa ◽  
Production Response

We have previously reported that, in conscious, unrestrained dogs in which insulin and glucagon levels were clamped pharmacologically, combined alpha- and beta-adrenergic blockade resulted simultaneously in a fall in plasma free fatty acid (FFA) levels and an increase in glucose production. In this study we have tested the hypothesis that the increase in glucose production observed in the previous study was due to the fall in plasma FFA concentration. Glucose production was measured by means of the primed-constant infusion of [6-3H]- and/or [U-14C]glucose, and insulin and glucagon were clamped at constant levels by means of the infusion of somatostatin, insulin, and glucagon. When no attempt was made to control the FFA levels, combined alpha- and beta-adrenergic blockade significantly decreased plasma FFA levels, and this was associated with a significant increase in the rate of glucose production. However, the glucose production response to adrenergic blockade was entirely prevented by the clamping of FFA levels at a high, constant value by the infusion of a 10% lipid emulsion (Liposyn) and heparin. We conclude that basal adrenergic activity is important in the mobilization of fat but does not directly influence glucose production. Further, there is an inhibitory effect of FFA on glucose production that is unmasked during hormonal control and alpha- and beta-adrenergic blockade.

Effect of burn trauma on glucose turnover, oxidation, and recycling in guinea pigs.

1977 ◽  
Vol 233 (2) ◽  
pp. E80
Author(s):  
R R Wolfe ◽  
J F Burke
Keyword(s):  
Clearance Rate ◽  
Guinea Pigs ◽  
Glucose Oxidation ◽  
Burn Injury ◽  
Constant Infusion ◽  
Glucose Turnover ◽  
Glucose Kinetics ◽  
Burn Trauma ◽  
Glucose Clearance ◽  
Low Rate

The simultaneous primed-constant infusion of [6-3H]- and [U-14C]glucose was used to determine the effect of burn injury on glucose turnover, oxidation, and recycling in guinea pigs. Eleven burned animals survived more than 72 h (survivors), whereas five died between 60 and 72 h postburn. All of the controls (n = 9) survived more than 72 h. At 48 h postburn, glucose turnover in the burned survivors was elevated 40% above that in control animals. A greater portion of the burned survivors' turnover was due to recycling and less was directed towards oxidation. The nonsurvivors had both a significantly depressed rate of appearance of glucose and an increased glucose clearance rate. Consequently, they were profoundly hypoglycemic and had a low rate of glucose oxidation. The alterations in glucose kinetics and oxidation apparent after burn did not reflect an inability of burned animals to oxidize exogenously infused glucose, however, because of 2-h infusion of 55 mumol/kg-min of unlabeled glucose doubled glucose oxidation in the burned survivors and tripled it in the nonsurvivors.

Adrenergic blockade prevents endotoxin-induced increases in glucose metabolism

1988 ◽  
Vol 255 (5) ◽  
pp. E629-E635 ◽  
Author(s):  
D. M. Hargrove ◽  
G. J. Bagby ◽  
C. H. Lang ◽  
J. J. Spitzer
Keyword(s):  
Plasma Insulin ◽  
Lactate Concentration ◽  
Insulin Concentration ◽  
Adrenergic Blockade ◽  
Plasma Lactate ◽  
Glucose Kinetics ◽  
Plasma Insulin Concentration ◽  
Beta Adrenergic ◽  
Plasma Lactate Concentration ◽  
Adrenergic Antagonists

Combined alpha- and beta-adrenergic blockade was used to investigate the role of catecholamines in endotoxin-induced elevations in glucose kinetics. Glucose kinetics were measured before and for 4 h after the injection of endotoxin [100 micrograms/100 g body wt iv, 30% lethal dose (LD30) at 24 h]. Adrenergic blockade was achieved by the bolus injection of phentolamine and propranolol followed by their continuous infusion. Endotoxin-treated rats exhibited a transient hyperglycemia and sustained (greater than 4 h) increase in plasma lactate concentration, as well as elevated rates of glucose appearance (Ra, 83%), disappearance (Rd, 58%), recycling (160%), and metabolic clearance (23%). Adrenergic blockade prevented endotoxin-induced increases in plasma glucose concentration, Ra, Rd, and recycling but not glucose clearance. The increase in plasma lactate concentration was blunted by 35%. After 2 h, endotoxic animals infused with adrenergic antagonists developed hypoglycemia, which may have resulted from an increased plasma insulin concentration. The attenuation of elevated glucose turnover by adrenergic blockade in the endotoxin-treated animals was not due to a reduction in plasma glucagon level or differences in plasma insulin concentration. Administration of the alpha- or beta-adrenergic antagonists separately blunted but did not prevent endotoxin-induced changes in glucose kinetics, and therefore the efficacy of the adrenergic blockade could not be assigned to a single receptor class. These results indicate that catecholamines are important contributory factors to many of the early alterations in carbohydrate metabolism observed during endotoxemia.

Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals

2007 ◽  
Vol 293 (6) ◽  
pp. R2376-R2381 ◽  
Author(s):  
Dorian S. Houser ◽  
Cory D. Champagne ◽  
Daniel E. Crocker
Keyword(s):  
Adult Female ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
High Rate ◽  
Constant Infusion ◽  
Substantial Contribution ◽  
Fasting Period ◽  
Elephant Seals ◽  
Glucoregulatory Hormones

Adult female elephant seals ( Mirounga angustirostris) combine long-term fasting with lactation and molting. Glycerol gluconeogenesis has been hypothesized as potentially meeting all of the glucose requirements of the seals during these fasts. To test this hypothesis, a primed constant infusion of [2-14C]glycerol was administered to 10 ten adult female elephant seals at 5 and 21–22 days postpartum and to 10 additional adult females immediately after the molt. Glycerol kinetics, rates of lipolysis, and the contribution of glycerol to glucose production were determined for each period. Plasma metabolite levels as well as insulin, glucagon, and cortisol were also measured. Glycerol rate of appearance was not significantly correlated with mass ( P = 0.14, r2 = 0.33) but was significantly related to the percentage of glucose derived from glycerol ( P < 0.01, r2 = 0.81) during late lactation. The contribution of glycerol to glucose production was <3% during each fasting period, suggesting a lower contribution to gluconeogenesis than is observed in other long-term fasting mammals. Because of a high rate of endogenous glucose production in fasting elephant seals, it is likely that glycerol gluconeogenesis still makes a substantial contribution to the substrate needs of glucose-dependent tissues. The lack of a relationship between glucoregulatory hormones and glycerol kinetics, glycerol gluconeogenesis, and metabolites supports the proposition that fasting elephant seals do not conform to the traditional insulin-glucagon model of substrate metabolism.

Investigation of kinetics of integrated metabolic response to adrenergic blockade in conscious dogs

1981 ◽  
Vol 241 (5) ◽  
pp. E385-E395
Author(s):  
R. R. Wolfe ◽  
M. J. Durkot ◽  
M. H. Wolfe
Keyword(s):  
Metabolic Response ◽  
Glucose Production ◽  
Hepatic Glycogen ◽  
Adrenergic Blockade ◽  
Fat Mobilization ◽  
Urea Production ◽  
Glucoregulatory Hormones ◽  
Plasma Ffa ◽  
Integrated Response ◽  
Glycerol Uptake

We have used multiple isotope infusions to study the integrated response of glucose, fat, and protein metabolism to combined alpha + beta-adrenergic blockade in conscious, unstressed, fasting (15 h) dogs. The response to the blocking agents was evaluated both with and without control of the glucoregulatory hormones. The hormones were controlled at the basal level by infusions of somatostatin and metyrapone to block their secretion, and by the infusion of insulin, glucagon, growth hormone, and cortisol at physiological rates. We found that adrenergic blockade markedly inhibited lipolysis, as reflected by falls in glycerol and plasma FFA appearance. The decrease in fat mobilization after blockade resulted in a proportionate shift from fat as an energy substrate toward carbohydrate. Glucose production and oxidation were both enhanced after blockade. The source of the increased glucose production was presumably hepatic glycogen because urea production was presumably hepatic glycogen because urea production was unaffected and glycerol uptake was decreased. These results are consistent with the interpretation that basal adrenergic activity plays an important role in the mobilization of fat in fasting dogs. A secondary consequence of that action is apparently a diminution of glucose production and oxidation, although the mechanism responsible for the latter response is not clear.

Influence of beta-hydroxybutyrate infusion on glucose and free fatty acid metabolism in dogs

1984 ◽  
Vol 247 (6) ◽  
pp. E756-E764 ◽  
Author(s):  
J. H. Shaw ◽  
R. R. Wolfe
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Sympathetic Activity ◽  
Glucose Production ◽  
The Other ◽  
Co2 Production ◽  
Constant Infusion ◽  
Adrenergic Blockade ◽  
Ffa Metabolism ◽  
Beta Hydroxybutyrate

We have investigated the effect of infusion of DL-beta-hydroxybutyrate (BOHB) (30 mumol X kg-1 X min-1) on glucose and free fatty acid (FFA) metabolism by means of the primed constant infusion of [U-14C]glucose and [1,2-13C]palmitic acid. The role of the hormonal response to the ketone infusion was assessed by controlling the hormone levels pharmacologically. In one group hormones were not controlled, while in the other two groups insulin and glucagon were maintained at constant levels by infusion of somatostatin, insulin, and glucagon at constant rates. In one of these hormonally controlled groups, combined alpha- and beta-adrenergic blockade was also employed. BOHB infusion increased total ketone concentration approximately 10-fold and, when hormones were not controlled, induced a significant increase in glucagon concentration. Regardless of hormonal status, elevation of the ketone levels decreased the rate of glucose production and FFA appearance. Glucose oxidation decreased in proportion to the reduction in the rate of glucose uptake in all groups. When sympathetic activity was not blocked an increase in the percent of FFA uptake oxidized enabled the percent CO2 production from FFA oxidation to remain constant despite the decrease in FFA uptake. However, when sympathetic activity was blocked the increase in the percent of FFA uptake oxidized observed in the other groups was prevented. We conclude from these studies that an elevation in ketone levels directly affects glucose and FFA metabolism independent of changes in insulin and glucagon levels and sympathetic activity.

Platelet-activating factor-induced increases in glucose kinetics

1988 ◽  
Vol 254 (2) ◽  
pp. E193-E200
Author(s):  
C. H. Lang ◽  
C. Dobrescu ◽  
D. M. Hargrove ◽  
G. J. Bagby ◽  
J. J. Spitzer
Keyword(s):  
Blood Pressure ◽  
Plasma Glucose ◽  
Infusion Rate ◽  
Bolus Injection ◽  
Platelet Activating Factor ◽  
Whole Body ◽  
Constant Infusion ◽  
Adrenergic Blockade ◽  
Glucose Kinetics ◽  
Infusion Period

Platelet-activating factor (PAF) is a postulated mediator of many of the early hemodynamic effects of endotoxin. The aim of the present study was to determine whether in vivo administration of PAF could produce alterations in whole-body glucose metabolism that would mimic those seen during endotoxemia. Glucose kinetics were assessed in chronically catheterized conscious rats by the constant infusion of [6-3H]- and [U-14C]glucose before and for 4 h after either a bolus injection (300 ng/kg) or a constant infusion (20 or 220 ng.min-1.kg-1) of PAF. The bolus injection of PAF produced a 30% decrease in blood pressure by 5 min that returned to control levels by 30 min. Increased plasma glucose (40%) and lactate (150%) levels after injection of PAF were also transient. In contrast, the bolus injection of PAF elevated the rate of glucose appearance (Ra; 44%) for 1.5 h. The lower PAF infusion rate decreased blood pressure 11% to 104 mmHg, whereas the higher infusion rate decreased pressure 34% to 77 mmHg. Both PAF infusion rates produced elevations in plasma glucose (28, 150%) and glucose Ra (20, 60%) throughout the 4-h infusion period in a dose-related manner. The PAF infusions also induced dose-related increases in plasma glucagon and catecholamine levels throughout the infusion period. In a separate group of experiments a complete adrenergic blockade, produced by the constant infusion of propranolol and phentolamine, completely prevented PAF-induced increases in glucose kinetics and the hyperglucagonemia.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effects of β-adrenergic blockade on hepatic and renal glucose production during hypoglycemia in conscious dogs

1998 ◽  
Vol 275 (5) ◽  
pp. E792-E797
Author(s):  
Eugenio Cersosimo ◽  
Irina N. Zaitseva ◽  
Mohamed Ajmal
Keyword(s):  
Glucose Production ◽  
Constant Infusion ◽  
Hepatic Veins ◽  
Adrenergic Blockade ◽  
Flow Probe ◽  
Before And After ◽  
Liver And Kidney ◽  
Arteriovenous Difference ◽  
Arterial Glucose

To investigate the role of β-adrenergic mechanisms in the counterregulatory response of the liver and kidney to hypoglycemia, we studied 10 dogs before and after a 2-h constant infusion of insulin (4 mU ⋅ kg−1 ⋅ min−1) either without ( n = 4) or with (8 μg/min, n = 6) propranolol and variable dextrose to maintain hypoglycemia, 7 days after surgical placement of sampling catheters in left renal and hepatic veins and femoral artery. Systemic glucose appearance (Ra) and endogenous (EGP), hepatic (HGP), and renal (RGP) glucose production were measured by a combination of arteriovenous difference and peripheral infusion of [6-3H]glucose, renal blood flow with a flow probe, and hepatic plasma flow by indocyanine green clearance. Without β-adrenergic blockade, arterial glucose decreased from 5.12 ± 0.02 to 2.53 ± 0.07 mmol/l, glucose Ra increased from 17.8 ± 0.7 to 30.5 ± 2.5 ( P< 0.01) when EGP was 22.2 ± 0.5, HGP from 13.5 ± 1.1 to 19.3 ± 1.3, and RGP from 2.4 ± 1.0 to 8.6 ± 0.9 μmol ⋅ kg−1 ⋅ min−1(all P < 0.05). When propranolol was infused, glucose decreased from 5.97 ± 0.02 to 2.71 ± 0.03 mmol/l, glucose Ra increased from 16.3 ± 1.0 to 25.1 ± 1.6 when EGP was 9.9 ± 0.4, HGP decreased from 14.4 ± 0.7 to 10.4 ± 0.6, and RGP decreased from 3.8 ± 1.3 to 1.1 ± 0.8 μmol ⋅ kg−1 ⋅ min−1(all P < 0.05). Our data indicate that β-adrenergic blockade impairs glucose recovery during sustained hypoglycemia, in part, by preventing the simultaneous compensatory increase in HGP and RGP.

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