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.

Studies on the carbohydrate metabolism of sheep. III. The blood glucose during insulin hypoglycaemia

1951 ◽  
Vol 2 (2) ◽  
pp. 132 ◽  
Author(s):  
RL Reid
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Carbohydrate Metabolism ◽  
Glucose Level ◽  
Insulin Injection ◽  
Experimental Results ◽  
Intermediary Metabolism ◽  
Insulin Administration ◽  
Intravenous Insulin

The response of sheep to intravenous insulin administration in doses of 0.5-10.0 units per kg. body weight has been studied in detail. The rate of fall of blood glucose following insulin injection is considerably slower than in non-ruminants. Increasing the dosage of insulin from 1 to 5 units per kg., and sometimes to 10 units per kg., does not increase the depth of hypoglycaemia, but merely increases its duration. The blood-glucose level following such doses of insulin falls, in most sheep, to a level of 5-10 mg. per cent. and remains relatively constant until it returns to normal. At these levels, severe hypoglycaemic signs were never observed, even when the hypoglycaemia was of several hours' duration. These results are compared with those obtained by others on cattle and goats and it is suggested that the response of sheep to insulin is similar in all respects to that shown by cattle and goats. From a consideration of the experimental results, it is suggested that the differences in response to insulin between ruminants and non-ruminants may be due to fundamental differences in endocrine balance which, in turn, are conditioned by differences in intermediary metabolism.

Low-Dose Intravenous Insulin Infusion Versus Subcutaneous Insulin Injection: A Controlled Comparative Study of Diabetic Ketoacidosis

PEDIATRICS ◽  
1977 ◽  
Vol 59 (5) ◽  
pp. 733-738
Author(s):  
Stenvert L. S. Drop ◽  
Bertrand J. M. Duval-Arnould ◽  
Alan E. Gober ◽  
Joseph H. Hersh ◽  
Paul T. McEnery ◽  
...  
Keyword(s):  
Diabetic Ketoacidosis ◽  
Insulin Infusion ◽  
Low Dose ◽  
Insulin Injection ◽  
Serum Glucose ◽  
Constant Infusion ◽  
Control Group ◽  
Study Group ◽  
Insulin Administration ◽  
Intravenous Insulin

Fourteen patients, 5 to 17 years old, with 18 episodes of uncomplicated diabetic ketoacidosis were randomly allocated and studied prospectively. The study group received 0.1 units of insulin per kilogram of body weight per hour as a continuous intravenous infusion: the control group received insulin subcutaneously. In both groups, a gradual fall in serum glucose and ketone levels was achieved. Serum ketones persisted longer in the intravenous group. No complications were encountered. The study suggests that both regimens of insulin administration are equally effective, but a low-dose constant infusion may provide more simplified and controlled management than the standard subcutaneous regimen.

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.

SECRETION OF β-ENDORPHIN INTO THE MATERNAL CIRCULATION BY UTEROPLACENTAL TISSUES IN RESPONSE TO HYPOGLYCAEMIC STRESS

1988 ◽  
Vol 118 (2) ◽  
pp. R5-R8 ◽  
Author(s):  
J. Falconer ◽  
E.-C. Chan ◽  
G. Madsen ◽  
M. Thomson ◽  
J. Davies ◽  
...  
Keyword(s):  
Analysis Of Variance ◽  
Femoral Artery ◽  
Plasma Concentrations ◽  
Insulin Injection ◽  
Plasma Samples ◽  
Maternal Circulation ◽  
Pregnant Uterus ◽  
Intravenous Insulin ◽  
Pregnant Sheep

ABSTRACT The placenta has been shown to contain ACTH and β-endorphin but the roles of these peptides are unknown. To investigate whether they are released into the maternal circulation from the placenta in response to physiological stimuli the effects of hypoglycaemic stress were investigated. Plasma samples were collected from the femoral artery (FA) and uterovarian (UV) vein of nine pregnant sheep before and during hypoglycaemia induced by intravenous insulin (100U). Plasma concentrations of ovine β-endorphin (oβ-EP) were measured by radioimmunoassay. Concentrations of oβ-EP rose in both vessels by 60 min after insulin. The peak concentrations of oβ-EP (pmol/l) were 122 ± 29 (mean ± SEM, n=8) in the UV and 96±24 (n=9) fmol/ml in the FA 60 min after insulin injection. There was no difference between the concentrations of oβ-EP in the vessels before insulin injection but at 60 and 120 min after insulin the concentrations of oβ-EP were significantly higher in the UV than FA (P<0.02, analysis of variance). This indicates that the pregnant uterus or placenta can respond to hypoglycaemia by secreting β-EP into the maternal circulation. It is therefore possible that placental pro-opiomelanocortin (POMC) peptides may have a role in maternal endocrinology and metabolism.

scholarly journals Glucose-Induced Insulin Hypersecretion in Lipid-Infused Healthy Subjects Is Associated with a Decrease in Plasma Norepinephrine Concentration and Urinary Excretion

2001 ◽  
Vol 86 (10) ◽  
pp. 4901-4907 ◽  
Author(s):  
Christophe Magnan ◽  
Céline Cruciani ◽  
Laurence Clément ◽  
Pierre Adnot ◽  
Mylène Vincent ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Urinary Excretion ◽  
Healthy Subjects ◽  
Plasma Concentrations ◽  
Sympathetic Tone ◽  
Plasma Norepinephrine ◽  
C Peptide ◽  
Lipid Infusion ◽  
Hyperglycemic Clamp ◽  
Glucose Injection

We investigated the effect of a 48 h triglyceride infusion on the subsequent insulin secretion in response to glucose in healthy men. We measured the variations in plasma concentration and urinary excretion of catecholamines as an indirect estimation of sympathetic tone. For 48 h, 20 volunteers received a triglyceride/heparin or a saline solution, separated by a 1-month interval. At time 48 h, insulin secretion in response to glucose was investigated by a single iv glucose injection (0.5 g/kg−1) followed by an hyperglycemic clamp (10 mg·kg−1·min−1, during 50 min). The triglyceride infusion resulted in a 3-fold elevation in plasma free fatty acids and an increase in insulin and C-peptide plasma concentrations (1.5- and 2.5-fold, respectively, P &lt; 0.05), compared with saline. At time 48 h of lipid infusion, plasma norepinephrine (NE) concentration and urinary excretion levels were lowered compared with saline (plasma NE: 0.65 ± 0.08 vs. 0.42 ± 0.06 ng/ml, P &lt; 0.05; urinary excretion: 800 ± 70 vs. 620 ± 25 nmol/24 h, P &lt; 0.05). In response to glucose loading, insulin and C-peptide plasma concentrations were higher in lipid compared with saline infusion (plasma insulin: 600 ± 98 vs. 310 ± 45 pm, P &lt; 0.05; plasma C-peptide 3.5 ± 0.2 vs. 1.7 ± 0.2 nm, P &lt; 0.05). In conclusion, in healthy subjects, a 48-h lipid infusion induces basal hyperinsulinemia and exaggerated insulin secretion in response to glucose which may be partly related to a decrease in sympathetic tone.

Hypoxic effect of exogenous insulin on normal and diabetic peripheral nerve

1994 ◽  
Vol 266 (6) ◽  
pp. E980-E985 ◽  
Author(s):  
M. Kihara ◽  
P. J. Zollman ◽  
I. L. Smithson ◽  
T. D. Lagerlund ◽  
P. A. Low
Keyword(s):  
Blood Flow ◽  
Peripheral Nerve ◽  
Oxygen Tension ◽  
Glycosylated Hemoglobin ◽  
Diabetic Rats ◽  
Insulin Administration ◽  
Dissociation Curve ◽  
Nerve Blood Flow ◽  
Intravenous Insulin ◽  
Arteriovenous Shunts

Insulin administration can cause or worsen experimental and human diabetic neuropathy ("insulin neuritis"). In this study, we tested the hypothesis that insulin administration impairs tissue oxygenation. We infused insulin under nonhypoglycemic conditions and evaluated its effect on endoneurial oxygen tension, nerve blood flow, and the oxyhemoglobin dissociation curve of peripheral nerve in normal and diabetic rats. Intravenous insulin infusion resulted in a dose-dependent reduction in endoneurial oxygen tension in normal nerves (from 26% at 0.04 U/kg insulin to 55% at 32 U/kg). The nerves of rats with streptozotocin-induced diabetes were resistant, but with control of hyperglycemia this susceptibility to the endoneurial hypoxic effect of insulin returned. The reduction in endoneurial oxygen tension regressed with glycosylated hemoglobin (Y = 53.8-2.7X, where Y = %reduction in endoneurial oxygen tension and X = HbA1; r = 0.87; P = < 0.001). Diabetes or insulin administration resulted in only minimal and physiologically insignificant alterations in the oxygen dissociation curve and 2,3-diphosphoglycerate of sciatic nerve. Instead, insulin administration resulted in a reduction in nerve nutritive blood flow and an increase in arteriovenous shunt flow. When the latter was eliminated by the closure of arteriovenous shunts (infusion of 5-hydroxytryptamine), endoneurial oxygen reverted to normal. These findings indicate a deleterious vasoactive effect of insulin and may explain the development of insulin neuritis.

Management of Diabetes Resistant to Subcutaneous Insulin with Intravenous Insulin via an Implanted Infusion Pump

1988 ◽  
Vol 33 (2) ◽  
pp. 239-243 ◽  
Author(s):  
K.R. Paterson ◽  
I.W. Campbell ◽  
S.M. MacRury ◽  
D.G. Gilmour ◽  
A.C. MacCuish
Keyword(s):  
Treatment Option ◽  
Insulin Infusion ◽  
Rare Complication ◽  
Infusion Pump ◽  
Insulin Injection ◽  
Management Problem ◽  
Subcutaneous Insulin ◽  
Intravenous Insulin ◽  
Infusion Devices ◽  
Insulin Dependent

Diabetes resistant to conventional subcutaneous insulin injection is a rare complication of insulin-dependent diabetes which poses a major management problem. We report three cases treated for a total of over seven patient years with fully implanted insulin infusion devices. Technical difficulties with the devices and their operation have been substantial but the patients are much improved and hospitalisation has been dramatically reduced. We suggest that implanted insulin pumps are a real treatment option for patients with this unusual syndrome.

Exercise-dependent growth hormone release is linked to markers of heightened central adrenergic outflow

2000 ◽  
Vol 89 (2) ◽  
pp. 629-635 ◽  
Author(s):  
Arthur Weltman ◽  
Cathy J. Pritzlaff ◽  
Laurie Wideman ◽  
Judy Y. Weltman ◽  
Jeffery L. Blumer ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Regression Analysis ◽  
Exercise Intensity ◽  
Acute Exercise ◽  
Peak Plasma ◽  
Linear Regression Analysis ◽  
Plasma Concentrations ◽  
Intensity Change ◽  
Plasma Norepinephrine ◽  
The Difference

To test the hypothesis that heightened sympathetic outflow precedes and predicts the magnitude of the growth hormone (GH) response to acute exercise (Ex), we studied 10 men [age 26.1 ± 1.7 (SE) yr] six times in randomly assigned order (control and 5 Ex intensities). During exercise, subjects exercised for 30 min (0900–0930) on each occasion at a single intensity: 25 and 75% of the difference between lactate threshold (LT) and rest (0.25LT, 0.75LT), at LT, and at 25 and 75% of the difference between LT and peak (1.25LT, 1.75LT). Mean values for peak plasma epinephrine (Epi), plasma norepinephrine (NE), and serum GH concentrations were determined [Epi: 328 ± 93 (SE), 513 ± 76, 584 ± 109, 660 ± 72, and 2,614 ± 579 pmol/l; NE: 2.3 ± 0.2, 3.9 ± 0.4, 6.9 ± 1.0, 10.7 ± 1.6, and 23.9 ± 3.9 nmol/l; GH: 3.6 ± 1.5, 6.6 ± 2.0, 7.0 ± 2.0, 10.7 ± 2.4, and 13.7 ± 2.2 μg/l for 0.25, 0.75, 1.0, 1.25, and 1.75LT, respectively]. In all instances, the time of peak plasma Epi and NE preceded peak GH release. Plasma concentrations of Epi and NE always peaked at 20 min after the onset of Ex, whereas times to peak for GH were 54 ± 6 (SE), 44 ± 5, 38 ± 4, 38 ± 4, and 37 ± 2 min after the onset of Ex for 0.25–1.75LT, respectively. ANOVA revealed that intensity of exercise did not affect the foregoing time delay between peak NE or Epi and peak GH (range 17–24 min), with the exception of 0.25LT ( P < 0.05). Within-subject linear regression analysis disclosed that, with increasing exercise intensity, change in (Δ) GH was proportionate to both ΔNE ( P = 0.002) and ΔEpi ( P = 0.014). Furthermore, within-subject multiple-regression analysis indicated that the significant GH increment associated with an antecedent rise in NE ( P = 0.02) could not be explained by changes in Epi alone ( P = 0.77). Our results suggest that exercise intensity and GH release in the human may be coupled mechanistically by central adrenergic activation.

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