Effect of functional adrenalectomy on glucagon secretion and circulating catecholamines during insulin hypoglycemia in the dog

1990 ◽  
Vol 68 (9) ◽  
pp. 1183-1188 ◽  
Author(s):  
Nobuharu Yamaguchi ◽  
Richard Briand ◽  
Rania Gaspo
Keyword(s):  
Sham Group ◽  
Venous Blood ◽  
Glucagon Secretion ◽  
Insulin Injection ◽  
Systemic Circulation ◽  
Sodium Pentobarbital ◽  
Insulin Administration ◽  
Insulin Hypoglycemia ◽  
Control Value ◽  
Bolus Insulin

The present study was carried out to determine whether an increase in the pancreatic immunoreactive glucagon (IRG) secretion during the acute phase of insulin-induced hypoglycemia depends on circulating catecholamines of adrenal origin. Hypoglycemia was induced by a bolus insulin injection (0.15 IU/kg, i.v.) in dogs anesthetized with sodium pentobarbital (35 mg/kg, i.v.). Plasma aortic epinephrine (E) and norepinephrine (NE) concentrations increased significantly 30 min after the injection of insulin. At this time point, a functional adrenalectomy (diversion of bilateral adrenal venous blood from the systemic circulation) was performed for 5 min. The increased aortic E and NE concentrations significantly decreased reaching, within 5 min, a level below the corresponding preinjection control value. The basal output of pancreatic IRG (6.58 ± 1.12 ng/min, n = 6) significantly increased (24.93 ± 2.77 ng/min, p < 0.05, n = 6) 30 min after insulin injection. During the functional adrenalectomy, the increased pancreatic IRG output diminished rapidly, within 5 min, to approximately 50% (11.73 ± 3.19 ng/min, p < 0.05, n = 6) of the value observed 30 min after insulin administration. In the other group of dogs receiving sham adrenalectomy, the increased aortic E and NE concentrations and pancreatic IRG output following insulin injection remained elevated above the levels observed immediately before the sham adrenalectomy. The net decrease in IRG output during the adrenalectomy was significant (p < 0.05) compared with the corresponding net IRG output observed in the sham group. The net changes in pancreatic IRG output after insulin administration and during adrenalectomy observed in both groups were correlated with those in aortic E and NE concentrations (r = 0.720, p < 0.05). The study shows that the increase in pancreatic IRG secretion during the early phase of insulin-induced hypoglycemia is due, in part, to the increased circulating catecholamines of adrenal origin.Key words: catecholamine, adrenal, pancreas, glucagon, insulin, hypoglycemia, adrenalectomy.

Direct evidence that an increase in aortic norepinephrine level in response to insulin-induced hypoglycemia is due to increased adrenal norepinephrine output

1989 ◽  
Vol 67 (5) ◽  
pp. 499-505 ◽  
Author(s):  
Nobuharu Yamaguchi ◽  
Richard Briand ◽  
Martine Brassard
Keyword(s):  
Direct Evidence ◽  
Plasma Concentrations ◽  
Insulin Injection ◽  
Plasma Norepinephrine ◽  
Sodium Pentobarbital ◽  
Insulin Administration ◽  
Norepinephrine Level ◽  
Intravenous Insulin ◽  
Aortic Blood ◽  
Initial Control

This study reports on the major source of circulating norepinephrine that is known to increase, progressively, during sustained hypoglycemia induced by intravenous insulin administration. Plasma concentrations of epinephrine, norepinephrine, and dopamine were simultaneously determined for adrenal venous and aortic blood in dogs anesthetized with sodium pentobarbital. The model used allowed us to perform a functional adrenalectomy (ADRX), while continuously monitoring the adrenal medullary secretory function. Under basal conditions, the net output (μg/min) of adrenal epinephrine, norepinephrine, and dopamine were 0.169 ± 0.074, 0.067 ± 0.023, and 0.011 ± 0.003, respectively. Plasma concentrations (ng/mL) of aortic epinephrine, norepinephrine, and dopamine were 0.132 ± 0.047, 0.268 ± 0.034, and 0.034 ± 0.009. Following insulin injection (0.15 IU/kg, i.v.), the net output (μg/min) of adrenal epinephrine, norepinephrine, and dopamine increased gradually (p < 0.05), reaching the values of 0.918 ± 0.200, 0.365 ± 0.058, and 0.034 ± 0.007 30 min after insulin administration. Similarly, aortic epinephrine, norepinephrine, and dopamine concentrations (ng/mL) increased significantly (p < 0.05) to 0.702 ± 0.144, 0.526 ± 0.093, and 0.066 ± 0.024. The aortic glucose concentration (mg/dL) was diminished from 81.8 ± 4.1 to 36.9 ± 3.4 (p < 0.01). After taking the blood sample at 30 min following insulin administration, ADRX was immediately performed. Five minutes after the onset of ADRX, the net output (μg/min) of adrenal epinephrine, norepinephrine, and dopamine increased further to 1.707 ± 0.374 (p < 0.05), 0.668 ± 0.139 (p < 0.05), and 0.052 ± 0.017. By contrast, aortic epinephrine, norepinephrine, and dopamine concentrations rapidly diminished (p < 0.05) to their initial control levels reaching 0.051 ± 0.014, 0.252 ± 0.023, and 0.031 ± 0.005 ng/mL, 5 min after ADRX. The present results indicate that during the early phase of insulin-induced hypoglycemia, circulating norepinephrine in aortic blood significantly increases due, primarily, to the enhanced adrenal norepinephrine output.Key words: insulin, plasma norepinephrine, adrenal catecholamines, functional adrenalectomy, hypoglycemia.

Selective hypoglycemia in the liver induces adrenomedullary counterregulatory response

1996 ◽  
Vol 270 (6) ◽  
pp. R1307-R1316 ◽  
Author(s):  
L. Lamarche ◽  
N. Yamaguchi ◽  
F. Peronnet
Keyword(s):  
Jugular Vein ◽  
Average Rate ◽  
Venous Blood ◽  
Systemic Circulation ◽  
Control Group ◽  
Insulin Administration ◽  
Normal Range ◽  
Aortic Blood ◽  
Hepatic Venous Blood ◽  
Normoglycemic Control

The present study was designed to investigate adrenal medullary responses to a selective regional hypoglycemia in the liver of dogs with hepatic cross-perfusion. The liver of recipient dogs (Rc) was perfused with vena caval and aortic blood of donor dogs (Dn) through the portal vein and hepatic artery, respectively. Total hepatic venous blood of Rc was returned to Dn through the left jugular vein. Upon the cross-perfusion, glucose (Glc, 5%) was infused at an average rate of 3.5 +/- 0.2 mg.kg-1.min-1 (n = 12) in Rc to compensate the loss of hepatic Glc delivery into the systemic circulation. Insulin (5.0 IU/kg i.v.) was administered to Dn followed by infusion with an average rate of 0.95 +/- 0.17 IU kg-1.min-1 (n = 6), and this served as the hepatic hypoglycemic group. Saline was similarly administered to Dn, which served as the normoglycemic control group. In the hepatic hypoglycemic group, aortic and vena caval Glc levels in Dn, which represent Glc concentrations entering the liver of Rc, decreased from 129.9 +/- 7.1 and 122.5 +/- 7.8 to 44.6 +/- 6.1 and 38.0 +/- 5.9 mg/dl (P < 0.05) 45 min after insulin administration, respectively. During this regional hepatic hypoglycemia in Rc, the systemic glycemia being kept within a normal range, adrenal epinephrine and norepinephrine output increased from 245.5 +/- 55.8 and 39.1 +/- 9.9 to 618.9 +/- 180.4 and 134.3 +/- 52.7 ng/min (P < 0.05), respectively. By contrast, aortic Glc and insulin levels in Dn of the normoglycemic control group remained unchanged, as did adrenal epinephrine and norepinephrine output in Rc. The results indicate that the regional hepatic hypoglycemia can significantly increase adrenal catecholamine secretion even during systemic (central) normoglycemia. The study suggests that the hepatoadrenal Glc counter-regulatory reflex may be functionally implicated in insulin-induced hypoglycemia.

Hepatic denervation reduces adrenal catecholamine secretion during insulin-induced hypoglycemia

1995 ◽  
Vol 268 (1) ◽  
pp. R50-R57 ◽  
Author(s):  
L. Lamarche ◽  
N. Yamaguchi ◽  
F. Peronnet
Keyword(s):  
Sham Group ◽  
Adrenal Glands ◽  
Maximum Level ◽  
Insulin Injection ◽  
Immunoreactive Insulin ◽  
Control Value ◽  
Afferent Nerves ◽  
Anesthetized Dogs ◽  
Series Of Experiments ◽  
The Difference

The present study was designed to investigate the functional implication of hepatic afferent nerves in controlling adrenal medullary counterregulatory response to insulin-induced hypoglycemia in anesthetized dogs subjected to an acute surgical denervation of the liver. Aortic glucose concentration decreased similarly in the groups of dogs with hepatic denervation (n = 8) and sham denervation (n = 8) reaching a glucose nadir 30 min after insulin injection (0.15 IU/kg i.v.) from a control value of 89.46 +/- 3.15 and 88.91 +/- 2.86 mg/dl to 52.92 +/- 3.27 and 48.80 +/- 4.18 mg/dl (P < 0.05), respectively. The catecholamine output from the adrenal glands in the sham group significantly increased (P < 0.05), reaching a maximum level 45 min after insulin injection from a control value for epinephrine of 86.35 +/- 26.65 ng/min and for norepinephrine of 32.14 +/- 11.68 ng/min to 659.03 +/- 269.39 and 181.21 +/- 63.03 ng/min, respectively. By contrast, however, adrenal catecholamine output increased only slightly in the hepatic-denervated group during insulin-induced hypoglycemia, from 148.37 +/- 95.29 and 52.06 +/- 28.05 ng/min to 210.49 +/- 96.09 and 79.61 +/- 26.11 ng/min for epinephrine and norepinephrine, respectively, the difference being statistically nonsignificant compared with the corresponding preinjection control value. The maximum net response of adrenal epinephrine and norepinephrine output observed in dogs with hepatic denervation was significantly attenuated by approximately 90 and 82% of the values obtained from the sham group, respectively. In a separate series of experiments, aortic immunoreactive insulin and glucagon concentrations were measured and found to be similar between hepatic-denervated and sham-denervated groups after insulin-induced hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Transhepatic absorption and biliary excretion of insulin

1987 ◽  
Vol 65 (9) ◽  
pp. 1982-1987 ◽  
Author(s):  
Walter Zingg ◽  
Aron M. Rappaport ◽  
Bernard S. Leibel
Keyword(s):  
Intravenous Administration ◽  
Biliary Excretion ◽  
Venous Blood ◽  
Intraperitoneal Administration ◽  
Liver Cells ◽  
Insulin Concentration ◽  
Secretory Process ◽  
Insulin Administration ◽  
Hepatic Cells ◽  
Liver Surface

The application of insulin to the liver in rats is followed by an increase of the insulin concentration in the bile. The pathway of insulin from the liver surface to the bile may include a secretory process by the hepatic cells, or it may bypass the hepatic cells, using direct anatomical pathways from blood and lymph to bile. The concentration of insulin in arterial and venous blood, in lymph, and in bile was measured following application of insulin to the liver surface and following peritoneal or intravenous administration. The results confirm that insulin is absorbed from the surface of the liver, but the glucose modulating effect was less effective than after intravenous administration. The insulin concentration in bile was increased after insulin administration by all routes, with the highest and most prolonged increases found after intraperitoneal administration. The results suggest that following transhepatic and intravenous administration, insulin reaches the bile without passing through the liver cells.

Effects of PACAP1–27 on the canine endocrine pancreas in vivo: interaction with cholinergic mechanism

2003 ◽  
Vol 81 (7) ◽  
pp. 720-729 ◽  
Author(s):  
Nobuharu Yamaguchi ◽  
Tamar Rita Minassian ◽  
Sanae Yamaguchi
Keyword(s):  
Endocrine Pancreas ◽  
Venous Blood ◽  
Insulin Response ◽  
Glucagon Secretion ◽  
Venous Blood Flow ◽  
Dependent Manner ◽  
Cholinergic Mechanism ◽  
Insulin And Glucagon Secretion ◽  
Anesthetized Dogs

The aim of the present study was to characterize the effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the endocrine pancreas in anesthetized dogs. PACAP1–27 and a PACAP receptor (PAC1) blocker, PACAP6–27, were locally administered to the pancreas. PACAP1–27 (0.005–5 μg) increased basal insulin and glucagon secretion in a dose-dependent manner. PACAP6–27 (200 μg) blocked the glucagon response to PACAP1–27 (0.5 μg) by about 80%, while the insulin response remained unchanged. With a higher dose of PACAP6–27 (500 μg), both responses to PACAP1–27 were inhibited by more than 80%. In the presence of atropine with an equivalent dose (128.2 μg) of PACAP6–27 (500 μg) on a molar basis, the insulin response to PACAP1–27 was diminished by about 20%, while the glucagon response was enhanced by about 80%. The PACAP1–27-induced increase in pancreatic venous blood flow was blocked by PACAP6–27 but not by atropine. The study suggests that the endocrine secretagogue effect of PACAP1–27 is primarily mediated by the PAC1 receptor, and that PACAP1–27 may interact with muscarinic receptor function in PACAP-induced insulin and glucagon secretion in the canine pancreas in vivo.Key words: atropine, PACAP, PAC1, muscarinic, interaction.

The Generation of Kinins in the Blood of Dogs during Hypotension Due to Haemorrhage

1970 ◽  
Vol 39 (3) ◽  
pp. 349-365 ◽  
Author(s):  
H. E. Berry ◽  
J. G. Collier ◽  
J. R. Vane
Keyword(s):  
Blood Pressure ◽  
Time Course ◽  
Venous Pressure ◽  
Venous Blood ◽  
Systemic Circulation ◽  
Substantial Effect ◽  
Mixed Venous Blood ◽  
Shed Blood ◽  
Arterial Blood ◽  
Organ Technique

1. Circulating kinins were detected and continuously assayed during hypotension due to haemorrhage in dogs, using the blood-bathed organ technique and isolated strips of cat jejunum as the assay tissue. 2. In arterial blood kinin concentrations of 1–5 ng/ml were attained after a hypotension of 35–65 mmHg had been maintained for 10–190 min. When portal venous blood was simultaneously assayed kinins appeared earlier and in concentrations 1–2 ng/ml higher than in arterial blood. No differences in time course of kinin generation or in concentration were found when mixed venous blood and arterial blood were compared. In those instances in which the blood pressure was restored to normal by returning the shed blood, kinin formation stopped. 3. Kinin generation was due to the presence in the circulation of a kinin-forming enzyme, such as kallikrein. When kallikrein was infused into the portal vein, it was partially inactivated by the liver. 4. Prolonged intravenous infusions of kallikrein (20–60 mu kg−1 min−1) generated kinins in the circulation in concentrations (1–5 ng/ml) which were well maintained throughout the infusion, demonstrating that kinin generation is not limited by depletion of the precursor kininogen; nevertheless, the effects of kallikrein infusions on the blood pressure and central venous pressure waned. 5. It is concluded that in hypotension due to haemorrhage, an active kallikrein appears in the portal circulation. Delay in the appearance of kallikrein in the systemic circulation may be due to the kallikrein inactivating mechanism of the liver. This inactivating mechanism may fail during shock. Kinins are generated in amounts sufficient to have a substantial effect on the circulation and an influence on the course of events in shock.

Studies on the Physiology of Awareness: An Oximetric Investigation of the Anoxaemia Accompanying Insulin Coma Therapy

1952 ◽  
Vol 98 (412) ◽  
pp. 411-420 ◽  
Author(s):  
John W. Lovett Doust ◽  
Robert A. Schneider
Keyword(s):  
Clinical Symptoms ◽  
Venous Blood ◽  
Insulin Injection ◽  
Personal Contact ◽  
Blood Oxygen Saturation ◽  
The Real ◽  
Arterial Blood ◽  
Schizophrenic Patients ◽  
Insulin Coma ◽  
Insulin Coma Therapy

This investigation deals with the measurement, by a peripheral method of discontinuous spectroscopic oximetry, of the arterial blood oxygen saturation levels in a group of schizophrenic patients undergoing insulin coma therapy.The association between tissue anoxia and insulin hypoglycaemia was first established by Campbell and Dudley in 1924. Dameshek and Meyerson (1935), using the arterio-venous oxygen difference method with the internal jugular vein as the source of venous blood, showed that the injection of insulin in coma doses was accompanied by an anoxaemia in the schizophrenic patients they studied. This work was confirmed by Himwich, Bowmanet al.(1939), and in another paper Himwich (1951, p. 277) and his co-workers found that the correlation of progressively developing clinical symptoms with the decrease of cerebral oxygen uptake was a closer one than the correlation with the more acute fall in the blood-sugar curve. An important symptomatic aspect of insulin hypoglycaemia includes the progressive changes in the levels of consciousness accompanying the approach towards coma. Wilder (1943) has outlined some of these changes, and Frostig (1940) and Himwich (1951, pp. 258-265) have delineated these awareness thresholds and discussed their relationship to the Hughlings Jackson theory of the phyletic organization of the central nervous system. Thus, during thefirst hourfollowing insulin injection, somnolence and lassitude appear to be associated with suppression of cortical and cerebellar activity; in thesecond hourfurther clouding of consciousness, sometimes with excitement, perceptual disturbances, periods of confusion, exacerbations of previously existing hallucinations and latent psychotic syndromes are seen; in thethird hourmotor restlessness and loss of consciousness suggest the release of basal ganglia and hypothalamus; in thefourth hourdeepening stupor and depression of exteroceptive sensitivity indicate a probable release of the midbrain and suppression of pyramidal function; in thefifth hourthe deep pre-mortal coma presages medullary release. Similarly, it is with awareness changes that many workers prefer to diagnose the “real coma” level in a patient under treatment. Thus Sakel (1937) held that coma was to be diagnosed when no further personal contact with the patient was possible, and Kalinowsky and Hoch (1946) agree that the real coma level is reached when it is completely impossible to awaken the patient.

scholarly journals Megakaryocytes in the Pulmonary Circulation

Blood ◽  
1963 ◽  
Vol 22 (1) ◽  
pp. 82-87 ◽  
Author(s):  
T. M. SCHEININ ◽  
A. P. KOIVUNIEMI
Keyword(s):  
Malignant Disease ◽  
Venous Blood ◽  
Systemic Circulation ◽  
Severe Anemia ◽  
Blood Samples ◽  
Direct Observations ◽  
Arterial Blood ◽  
Nonmalignant Disease ◽  
Abundant Cytoplasm ◽  
Pulmonary Arterial

Abstract The streptolysin 0 hemolysis method for isolation of cancer cells in the blood was employed for direct observations of the incidence and some characteristics of circulating megakaryocytes. In a series of 168 patients, circulating megakaryocytes were found in 77 per cent of the blood samples. Each sample contained an average of 1.2 megakaryocytes per ml. of blood. The megakaryocytes were most frequent in pulmonary arterial blood and a number of the cells had an apparently intact abundant cytoplasm. Pulmonary venous blood contained megakaryocytes much less frequently. These were almost always without cytoplasm or with only a narrow rim of it and as a rule small naked nuclei or their fragments were found. Manipulation of lung tissue resulted in an increased amount of megakaryocytes in the pulmonary venous blood. The megakaryocytes in pulmonary and systemic circulation were more numerous in advanced malignant disease than in early cases, and more common in inflammatory disease or severe anemia than in other nonmalignant disease.

RENAL CLEARANCE OF SODIUM AND POTASSIUM IN HYPOTHERMIA

1962 ◽  
Vol 40 (1) ◽  
pp. 113-122 ◽  
Author(s):  
G. S. Kanter
Keyword(s):  
Artificial Respiration ◽  
Plasma Potassium ◽  
Sodium Concentration ◽  
Plasma Sodium ◽  
Renal Tubules ◽  
Sodium Pentobarbital ◽  
Clearance Ratio ◽  
Control Value ◽  
The Difference ◽  
Sodium And Potassium

The handling of sodium and potassium by the renal tubules at various levels of hypothermia was studied. Fourteen dogs were anesthetized with 30 mg/kg sodium pentobarbital. After suitable control clearance measurements, the rectal temperature was lowered progressively by ice-packing to about 25 °C while renal clearances were continuously measured. Artificial respiration was not used. No change in plasma sodium was detected but plasma potassium fell significantly from a control value of 4.1 ± 0.09 meq/1. at 38 °C to 3.4 ± 0.12 meq/1. at 25 °C. Urine sodium concentration fell during exposure to cold while potassium concentration increased slightly. In spite of the marked fall in glomerular nitration rate (69.0 ± 3.1 ml/minute control to 17.0 ± 3.6 ml/minute at 25 °C) the final urine flow at 25 °C was slightly greater than that of control. The clearance ratios (in percentage) increased significantly, reflecting the marked decrease in tubular reabsorption: water, 0.49 ± 0.05 at 38 °C to 2.02 ± 0.25 at 25 °C; sodium, 0.47 ± 0.12 to 1.13 ± 0.27; potassium, 18.0 ± 2.6 to 54.0 ± 12.0. The difference in clearance ratio alterations is a reflection of the dissimilar effect of hypothermia on particular renal regulations.

Cardiovascular response to oxygen inhalation in the anesthetized cat

1961 ◽  
Vol 16 (5) ◽  
pp. 858-862 ◽  
Author(s):  
John A. Bevan ◽  
M. Anthony Verity
Keyword(s):  
Arterial Pressure ◽  
Cardiovascular Response ◽  
Hypotensive Effect ◽  
Second Phase ◽  
Sodium Pentobarbital ◽  
Control Value ◽  
Oxygen Inhalation ◽  
Significant Difference ◽  
Bilateral Vagotomy ◽  
Anesthetized Cat

An analysis of the cardiovascular response to short periods of inhalation of O2 is presented. In cats anesthetized with chloralose, an immediate acute fall in arterial pressure, accompanied by a varying degree of bradycardia was followed by an equilibrium state lower than the control value. Following bilateral vagotomy the initial hypotension was still present but the arterial pressure during the second phase returned to the preoxygen value. With inactivation of the caroticoaortic chemoreceptor regions, no hypotensive effect was seen, but a small, slowly developing hypertension was observed, originating peripherally. A similar, but significantly smaller hypotensive effect was seen in cats under sodium pentobarbital anesthesia. No significant difference in the arterial O2 saturation between animals anesthetized with chloralose and pentobarbital was noted, but in both groups the largest fall in arterial pressure occurred with the greater degree of anoxia. Experiments in which an increased degree of anoxemia was induced demonstrated the significantly different reactivity of the chemoreflex system under the anesthetics studied and suggests the presence of a central selective depression of the tonic anoxic chemoreceptor drive with barbiturate anesthesia. Submitted on February 27, 1961

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