Effect of Glucagon on Glucose Turnover and Plasma Free Fatty Acids in Depancreatized Dogs Maintained on Matched Insulin Infusions

1972 ◽  
Vol 50 (10) ◽  
pp. 946-954 ◽  
Author(s):  
A. Cherrington ◽  
M. Vranic ◽  
P. Fono ◽  
N. Kovacevic

It has been shown previously that glucagon can increase the turnover of glucose in normal dogs and can enhance the secretion of insulin. The aim of this study was to determine the metabolic effects of glucagon independent of the effects of the insulin it releases directly through an action on β cells, and indirectly through hyperglycemia. Eight conscious dogs which could not mobilize extra insulin were obtained by replacing the endogenous insulin secretion of each with an equivalent intraportal infusion of the hormone immediately following removal of a remnant pancreatic autograft. Such infusions (200 μU/kg-min) maintained normal plasma concentrations of glucose and free fatty acids (FFA), as well as normal tracer-determined rates of glucose appearance (Ra) and disappearance (Rd) prior to glucagon infusion.There was a highly significant regression of the increments in glucose production on the rate of glucagon infusion (1.00–3.00 μg/kg-h). Rd increased proportionally to glucose levels, and there was therefore no significant change in the metabolic clearance of glucose. Hence a direct inhibitory effect of glucagon on glucose utilization could not be demonstrated. Corrections for recycling of the infused label did not appreciably affect the observed changes in Ra or Rd. Glucagon infusions did not increase the FFA level in plasma; when hyperglycemia was prominent a small decrease occurred. The role of glucagon in the net release of FFA from adipocytes in dogs is therefore questioned.

1975 ◽  
Vol 53 (1) ◽  
pp. 124-128 ◽  
Author(s):  
Suzanne Rousseau-Migneron ◽  
Jacques LeBlanc ◽  
Louise Lafrance ◽  
Florent Depocas

Following a subcutaneous injection of adrenaline (300 μg/kg), blood-glucose levels were lower in rats treated chronically with adrenaline (300 μg/kg twice a day for 28 days) than in control rats during at least 2.5 h after the injection. To explain this difference of response, the turnover rate of glucose was measured in control and adrenaline-treated rats during adrenaline infusion (0.75 μg/kg−1 min−1), with [U-14C]glucose as tracer. It was found that the rate of appearance of glucose was greater in the control than in the adrenaline-treated group after a 120-min infusion of adrenaline. The rate of disappearance of glucose in the treated rats increased during the first 60 min of infusion and stayed at this elevated level for a subsequent 2 h, whereas in the control rats, it remained unchanged at the beginning of adrenaline infusion and significantly increased only during the second and third hours of infusion. In addition, the metabolic-clearance rate of glucose was not modified by adrenaline in the treated group, but in the control group, the initial clearance rate was significantly less than in the treated group, and decreased during the first hour of adrenaline infusion even though blood glucose reached values of 244 mg/100 ml. From these data, it is suggested that rats adapt to a chronic exogenous supply of adrenaline by a reduced increase in glucose production in response to adrenaline infusion and a better glucose utilization, which possibly indicates a decrease in the inhibitory effect of adrenaline on insulin secretion.


1976 ◽  
Vol 50 (5) ◽  
pp. 401-407
Author(s):  
I. A. Nimmo ◽  
R. H. Smith ◽  
M. A. Dolder ◽  
M. F. Oliver

1. The turnover of plasma glucose and free fatty acids was measured in ten patients within 24 h of the onset of symptoms of acute myocardial infarction and in two with symptoms of acute myocardial ischaemia. The measurements were repeated in seven of the patients 12–40 weeks after the acute episode. 2. Both for the patients with acute myocardial infarction alone and for all the individuals studied the turnover of glucose increased with plasma glucose concentration but was not related to the turnover of free fatty acids or the plasma concentrations of free fatty acids, insulin or total catecholamines. There was no obvious difference in the nature of the glucose turnover—concentration relationship between the patients with acute myocardial infarction, with acute myocardial ischaemia and on re-examination. 3. For all the individuals studied the turnover of free fatty acids increased with the concentration of these but was not related to the turnover of glucose or the plasma concentrations of glucose, insulin or total catecholamines. There was no obvious difference in the nature of the free fatty acids turnover—concentration relationship between the patients with acute myocardial infarction, with acute myocardial ischaemia and on re-examination.


1961 ◽  
Vol 16 (2) ◽  
pp. 339-341 ◽  
Author(s):  
William T. McElroy ◽  
John J. Spitzer

To assay changes in plasma free fatty acids (FFA) during a stress reported to activate a sympathetic discharge, dogs were made hypercapnic by inhaling mixtures of gases containing 15–30% CO2 in O2. Results showed that during such a maneuver, plasma FFA and glucose concentrations were elevated. Blood pH and heart rates were decreased and mean blood pressures fell in the early stage of hypercarbia, but gradually rose back to normal within 30 minutes. Dogs with adrenal glands occluded from the circulation showed little or no change in plasma concentrations of FFA or glucose, although blood pH and heart rates declined quantitatively the same as in intact dogs. 'Adrenalectomized' dogs were unable to reset lowered blood pressures at pre-CO2 levels when breathing 30% CO2. It is concluded that, during the stress of respiratory acidosis, a sympathetic discharge activates a release of adrenal medullary amines, and these in turn raise not only glucose levels, but also FFA, an important energy source. Submitted on August 22, 1960


2001 ◽  
Vol 91 (6) ◽  
pp. 2523-2530 ◽  
Author(s):  
Thomas Schricker ◽  
Ralph Lattermann ◽  
Pierre Fiset ◽  
Linda Wykes ◽  
Franco Carli

The aim of this study was to assess dynamic changes in protein and glucose metabolism during surgery. Twelve patients undergoing colorectal surgery received either intravenous propofol anesthesia ( n = 6) or inhalational anesthesia with desflurane ( n = 6). Pre- and intraoperative protein and glucose kinetics were analyzed by an isotope dilution technique usingl-[1-13C]leucine and [6,6-2H2]glucose. Plasma concentrations of glucose, lactate, free fatty acids, insulin, glucagon, and cortisol were measured before and after 2 h of surgery. The rates of appearance of leucine and glucose, leucine oxidation, protein synthesis, and glucose clearance decreased during surgery, independent of the type of anesthesia ( P < 0.05). A correlation between the rate of appearance of leucine and glucose was observed ( r = 0.755, P < 0.001). Intraoperative plasma cortisol and glucose concentrations increased ( P< 0.05), whereas plasma concentrations of lactate, free fatty acids, insulin, and glucagon did not change. Surgery causes a depression of whole body protein and glucose metabolism, independent of the anesthetic technique. There is a correlation between perioperative glucose production and protein breakdown.


1989 ◽  
Vol 257 (5) ◽  
pp. E686-E696 ◽  
Author(s):  
G. Paolisso ◽  
A. J. Scheen ◽  
A. Albert ◽  
P. J. Lefebvre

The purpose of the present study was to investigate the respective effects of continuous intravenous delivery of both insulin and glucagon compared with those of pulsatile insulin (and continuous glucagon), pulsatile glucagon (and continuous insulin) and both hormones administered in a pulsatile manner (but out of phase) on various parameters of glucose turnover. The study was performed on six healthy male volunteers submitted to a 325-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of pancreatic hormones was inhibited by somatostatin (2 micrograms/min). Four combinations of continuous and pulsatile infusions of insulin and glucagon were performed on different days and in random order. The amounts of hormone infused were identical in all instances and were 0.2 mU.kg-1.min-1 (continuous insulin), 67 ng/min (continuous glucagon), 1.3 mU.kg-1.min-1 and 435 ng/min with a switching on-off length of 2-11 min (for intermittent insulin and glucagon delivery, respectively). In the case of pulsatile administration of both hormones, the pulses of insulin and glucagon were given out of phase with a 6-min interval. Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classic methodology using a D-[3-3H]glucose infusion allowed to study glucose turnover. When compared with pulsatile insulin and continuous glucagon, pulsatile glucagon and continuous insulin were characterized by a significantly higher endogenous (hepatic) glucose production. When both insulin and glucagon were delivered in a pulsatile manner, the effect of pulsatile glucagon was predominant, maintaining a high endogenous glucose production. Under no circumstance was an effect on glucose utilization or clearance detected. This study demonstrates that pulsatile delivery of insulin or glucagon in humans has greater effects in modulating endogenous glucose production than continuous infusion. Furthermore, when both insulin and glucagon are delivered intermittently and out of phase, the stimulatory effect of glucagon on endogenous glucose production prevails over the inhibitory effect of insulin.


1997 ◽  
Vol 78 (5) ◽  
pp. 805-813 ◽  
Author(s):  
Kjell Holtenius ◽  
Paul Holtenius

The metabolic effects of a phlorizin-induced drainage of glucose were studied in six lactating ewes with or without peroral alanine drenches in a study of crossover design. Phlorizin gave rise to a small, but significant, elevation of plasma β-hydroxybutyrate. The plasma level of alanine decreased by about 30 % due to the phlorizin injections and alanine was negatively correlated to β-hydroxybutyrate. The plasma level of free fatty acids increased due to phlorizin. Plasma insulin and glucose concentrations were not significantly affected by phlorizin while glucagon level showed a small but significant increase. Peroral alanine drenches to phlorizin-treated ewes gave rise to a transitory elevation of alanine in plasma. The plasma level of free fatty acids was about 40 % lower in phlorizin-treated ewes receiving alanine and β-hydroxybutyrate tended to be lower (P < 0.08). We suggest that β-hydroxybutyrate, apart from its function as an oxidative fuel, might play an important role by limiting glucose oxidation and protein degradation in skeletal muscles during periods of negative energy balance in ruminants. Furthermore, it is suggested that alanine supplementation decreases lipolysis and ketogenesis in lactating ewes.


2009 ◽  
Vol 205 (1-6) ◽  
pp. 299-301 ◽  
Author(s):  
Harald Wang ◽  
Knut Rasmussen ◽  
Harald Vik-Mo ◽  
Ole D. Mjøs ◽  
Helge Grendahl

1986 ◽  
Vol 106 (2) ◽  
pp. 209-217 ◽  
Author(s):  
Sarah C. Bolton ◽  
T. E. C. Weekes

SUMMARYAdrenaline was infused at three rates, 40, 15 or 3 μ/kg/h, in normal sheep and in sheep rendered hypercortisolaemic by infusion of cortisol at 150 μg/kg/h. In both normal and hypercortisolaemic animals, plasma concentrations of glucose and free fatty acids were increased by adrenaline treatment; plasma phosphate decreased with all treatments; plasma magnesium and potassium decreased on infusion of adrenaline at 40 or 15, but not at 3 μg/kg/h; plasma calcium decreased only on infusion of adrenaline in hypercortisolaemic animals, and plasma sodium concentration was unaffected by treatment.Induction of a degree of lipolysis likely to occur in the field was not associated with a marked decrease in plasma magnesium.


1979 ◽  
Vol 236 (3) ◽  
pp. E255
Author(s):  
H L Lickley ◽  
G G Ross ◽  
M Vranic

To study the importance of glucagon and insulin in diabetes, somatostatin (ST) was infused, alone or with insulin or glucagon, in 11 conscious dogs. Plasma immunoreactive insulin (IRI) and glucagon (IRG) levels fell 65 +/- 4% and 33 +/- 3%, respectively, with somatostatin infusion. Glucose production (Ra) assessed by [3-3H]glucose, [2-3H]glucose, or [1-14C]glucose decreased transiently. This is in contrast to the rise in Ra seen after insulin withdrawal in depancreatized dogs, which have normal levels of IRG. Thus, suppression of IRG with somatostatin prevented an increase in Ra in spite of suppression of IRI. When near basal IRG levels were provided during ST infusion in normal dogs, Ra increased, indicating that glucagon contributes to the acute development of diabetes. When basal IRI levels were provided with ST, suppression of Ra was maintained, suggesting that the transience of the metabolic effects of ST-induced glucagon suppression requires concomitant insulin suppression. A comparison of glucose turnover measured using different tracers showed that ST-related hormonal changes did not alter the rate of futile cycling in the liver. ST induced a rise in plasma free fatty acid (FFA) levels, attributed solely to insulin deficiency, as glucagon suppression did not significantly alter FFA concentrations when normal insulin levels were maintained.


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