Glucagon responses to hypoglycemia in adrenalectomized man

In order to examine the possibility that epinephrine is involved in either the mediation or modulation of the enhanced glucagon release during glucopenia, glucagon responses to insulin-induced hypoglycemia were evaluated in four men with bilateral adrenalectomy in comparison with ten normal men. In the adrenalectomized patients, the mean nadir of plasma glucose and the rate of ascent to baseline levels were indistinguishable from those observed in normal subjects. Similarly, glucagon responses in the adrenalectomized group were not different from those encountered in the normal volunteers. We conclude that epinephrine does not contribute significantly to the augmented glucagon release during abrupt glucopenia in normal man and is not necessary for normal recovery from hypoglycemia.     

The source of circulating catecholamines in forced dived ducks

Plasma catecholamines have been measured in chronically adrenalectomized (ADX) ducks, in chronically adrenal-denervated ducks (DNX), and in their respective shamoperated controls (SH-adx, SH-dnx) after 3 min forced submergence. The results showed that 100% of the plasma epinephrine (EP) and 70 to 80% of plasma norepinephrine (NE) released during the dive came from the adrenal glands. Only 20 to 30% of plasma NE came from the endings of the autonomic vascular sympathetic nerves which are strongly stimulated during diving. Adrenal catecholamines were released by nerve activation only; nonneural mechanisms did not play any role in their release. The action of adrenal catecholamines on the cardiovascular system during dives was investigated by measuring heart rate and arterial blood pressure in operated and sham-operated ducks. Cardiovascular adjustments, associated with 3 min of forced diving, were not affected by any differences in the levels of plasma catecholamines.     

The influence of short term submaximal work on the plasma concentrations of catecholamines, pancreatic glucagon and growth hormone in man.

Studies were performed in 6 healthy, male volunteers to explore the effect of a work load on the blood concentrations of catecholamines in relation to pulse rate and blood pressure and the blood levels of pancreatic glucagon, insulin, growth hormone, glucose and glycerol. The work load consisted of 300 kpm/min for 5 min, followed by 600 kpm/min during the next 5 min and 900 kpm/min under a third 5 min period. The work load resulted in a marked increase in noradrenaline and adrenaline at 10 and 15 min of exercise. The pulse rate, the systolic pressure and the mean blood pressure were correlated to the blood levels of both adrenaline and noradrenaline. In spite of the rather marked activation of the sympathetic nervous system no increase occurred in glucagon as measured under exercise and up to 60 min after its completion. In 4 of the subjects the work load was followed by a prompt growth hormone response. The same 4 subjects also showed a marked increase in catecholamines. The 2 remaining subjects presented no change in growth hormone and their increase in catecholamines was relatively minor. Glycerol increased significantly during work and there was a positive correlation between the values recorded for glycerol and adrenaline. No significant changes occurred in blood sugar or insulin during work.     

Influence of physical training on the fuel-hormone response to prolonged low intensity exercise

The effects of physical training on the fuel-hormone response to prolonged (3 hr), low intensity cycle ergometer exercise (40% maximal aerobic power) which in the untrained state fails to produce a rise in blood lactate, was examined in six healthy male subjects. The training program consisted of one hour cycle ergometer exercise performed 4 times weekly for 6 weeks and resulted in a 19% increase in maximal aerobic power. Prior to training, prolonged low intensity exercise resulted in a 20% decline in plasma glucose, a 2.5-fold rise in plasma free fatty acids (FFA), a 7-fold rise in plasma epinephrine, a 3-fold elevation in plasma norepinephrine, and a 2.5-fold rise in plasma glucagon. Following training, the exercise-induced decline in glucose was 60% less than before training, the elevations in plasma FFA and norepinephrine were respectively, 45% and 90% less than before training and no significant increment in plasma norepinephrine and glucagon was observed. Training also blunted the exercise-induced elevations in circulating ketones and growth hormone and resulted in a lower respiratory exchange ratio during exercise. The data indicate that training markedly diminishes the fuel-hormone perturbations associated with low intensity exercise and in the face of a lessened increment in plasma FFA results in a greater utilization of fat and less dependence on carbohydrate during the exercise.     

Counterregulation of insulin-induced hypoglycaemia in primary hypothyroidism

Hypothyroidism has been alleged to modulate insulin action and influence the secretion of growth hormone and catecholamines. We recently investigated the influence of hypothyroidism on glucose counter-regulatory capacity and the hormonal responses to insulin-induced hypoglycaemia in 6 patients with primary hypothyroidism (age 32-52 years, TSH-values 66-200 mU/l). Hypoglycaemia was induced in the hypothyroid state and again when the subjects were euthyroid. After an overnight fast a constant rate infusion of insulin (2.4 U/h) was given for 4 h. Glucose was measured every 15 min and insulin. C-peptide, glucagon, epinephrine, norepinephrine, growth hormone and cortisol every 30 min for 5 h. During insulin infusion somewhat higher concentrations of the hormone were obtained in the hypothyroid state and simultaneously glucose levels were 0.5 mmol/l lower. As expected, basal norepinephrine levels were higher in hypothyroidism. However, no increase in circulating norepinephrine during hypoglycaemia was registered in the two experiments. The responses of counterregulatory hormones showed an enhanced response of cortisol, similar responses of growth hormone and epinephrine while the glucagon response was paradoxically impaired. Our findings suggest that hypothyroidism alters insulin metabolism, and that the glucagon response to hypoglycaemia is impaired in this condition.     

Effect of glucagon and glucose load on glucose kinetics, plasma FFA, and insulin in dogs treated with methylprednisolone

Glucose turnover, plasma lactate, FFA, and insulin levels were measured on trained, unanesthetized dogs with indwelling arterial and venous catheters. 2-t-Glucose was used as a tracer according to the primed-constant rate infusion technique to estimate the rate of appearance (R_a) of glucose in and its disappearance (R_d) from the plasma. After establishing base-line values, glucagon (30 or 60 ng/kg/min) or glucose (4.5, 7.5, or 15 mg/kg/min) was infused for 135 min. In normal dogs, glucagon increased the plasma $\text{glucose +}\text{14 mg}\text{100 ml}$, R_a + 1.2 mg/kg/min and caused a transient decrease of plasma FFA. Three days of treatment with methylprednisolone (3–3.5 mg/kg/day) almost doubled the glucose turnover at only slightly elevated plasma glucose and insulin levels. This treatment strikingly potentiated the effect of glucagon on the hepatic glucose output (20-fold) and on plasma sugar (12-fold). In these animals, glucagon also caused a greater decrease of FFA and a greater rise of insulin levels. Plasma lactate was not altered significantly by glucagon. Infusion of glucose decreased R_a and increased R_d to nearly the same extent in both groups. However, the FFA lowering effect of glucose infusion was less pronounced after glucocorticoid treatment. It is concluded that one of the most spectacular consequences of a brief treatment with large doses of glucocorticoid is the greatly increased effect of glucagon on hepatic glycogenolysis. The possible mechanism of this synergism is discussed.     

Adrenoceptor antagonists, but not guanethidine, reduce glucopenia-induced glucagon secretion from perfused rat pancreas

This study was designed to investigate (1) whether norepinephrine is released in response to glucopenia in vitro, thereby stimulating glucagon secretion and, (2) the modulating effects of norepinephrine on insulin and glucagon secretion, using isolated perfused rat pancreas preparations. Simultaneous addition of the adrenergic receptor antagonists yohimbine, prazosin and propranolol, each at a concentration of 10⁻⁵ mol/l, significantly potentiated glucose-stimulated insulin secretion (6.23 ± 0.76 vs. 2.11 ± 0.72 (control) nmol/min, P < 0.01), and suppressed glucopenia-induced glucagon secretion (0.59 ± 0.10 vs. 1.34 ± 0.18 (control) ng/min, P < 0.05). Also, 10⁻⁵ mol/l yohimbine alone significantly potentiated glucose-stimulated insulin secretion (4.86 ± 0.50 nmol/min, P < 0.05). The norepinephrine release inhibitor, guanethidine, significantly inhibited tyramine-induced secretion of both norepinephrine (7.86 ± 0.77 vs. 49.7 ± 2.3 nmol/min, P < 0.01) and glucagon (0.31 ± 0.08 vs. 1.21 ± 0.15 ng/min, P < 0.01), but exerted no effects on glucopenia-induced secretion of either norepinephrine or glucagon. We conclude that these results further support the concept that the neurotransmitter norepinephrine is released in response to glucopenia in vitro, and modulates insulin and glucagon secretion. Our data do not, however, provide evidence indicating that glucopenia-induced glucagon secretion is mainly mediated by activation of sympathetic nerve terminals around the -cells in the isolated perfused rat pancreas.     

Alteration by fasting of the effects of methylprednisolone on carbohydrate metabolism in the normal dog

Replacement regimen of cortisol was found to increase hepatic glucose release and overall glucose uptake by tissues (glucose turnover) in the postabsorptive adrenalectomized or hypophysectomized dog, but had no effect in the normal dog. A more potent glucocorticoid, methylprednisolone, has been reported to increase glucose turnover in the normal dog. In the present study, measurements of glucose turnover are correlated with measurements of liver glycogen and of plasma glucose, lactate and insulin. The studies were done in normal postabsorptive and starved dogs, in the control state and during a methylprednisolone regimen. Glucose turnover was measured in unanesthetized, trained dogs, using glucose -6-¹⁴C, which was administered in tracer amounts as a priming injection following immediately by a constant infusion. Methylprednisolone (2–2.5 mg/kg/day for 3–4 days) increased glucose turnover in the postabsorptive state. Plasma glucose concentration was unchanged, but lactate and insulin levels were elevated and liver glycogen was markedly increased. Fasting for 5 days decreased glucose turnover as well as liver glycogen and plasma insulin, with little change in plasma levels of glucose and lactate. Administration of methylprednisolone for 3–4 days with continuation of the fast did not alter significantly the plasma levels of glucose and lactate, but insulin levels increased to values seen in the postabsorptive state. The most striking effect was the increase in liver glycogen from the low values of the long-fasted state to values exceeding those in the postabsorptive state. Despite the elevated glycogen content hepatic glucose release (and turnover) was not increased above the depressed values of the long-fasted state. It was established that these glycogen stores could be mobilized by glucagon infusion.     

Stimulative effects of TMB-8 and trifluoperazine on pancreatic hormone release

The effects of 8-N-N-diethylamino octyl 3,4,5-trimethoxybenzoate (TMB-8) and trifluoperazine (TFP) on the early phase (10 min) of the release of pancreatic hormones from isolated rat islets were investigated. TMB-8 and TFP stimulated insulin, glucagon, and somatostatin release in a dose-dependent manner at a low glucose concentration (2.5 mM). The levels of glucagon and somatostatin release were also stimulated by these two agents at a high glucose concentration (10 mM). Their effects were independent of external calcium ion level. These two agents did not modify insulin release at the high glucose concentration. The stimulative effects of the two agents on the release of these hormones were partially suppressed when the islets were pretreated with 6-hydroxydopamine (6-OHDA), a chemical adrenergic denervator that acts at nerve endings. In this situation, the norepinephrine (NE) released from pancreatic islets decreased to 44% of that of non-treated islets (P less than 0.01). The addition of NE (10(-9) M) to the incubation medium increased insulin, glucagon, and somatostatin secretion by 20-30% over control levels (P less than 0.05). In conclusion, the early phase of pancreatic hormone release was stimulated by TMB-8 and TFP. Our results strongly suggest that these two drugs could be mediated by the NE released from nerve endings in the islets.     

Role of glucagon in hyperglycemic response during a short period of hemorrhage in anesthetized dogs

A role of pancreatic glucagon in hemorrhage induced hyperglycemia was studied in anesthetized dogs with or without functional adrenalectomy (ADRX), surgical hepatic denervation (HNX), and surgical pancreatectomy (PCX). Plasma epinephrine, norepinephrine, and glucose concentrations were determined in both hepatic venous and aortic blood. Plasma glucagon (IRG) and insulin (IRI) levels were determined in aortic blood. All dogs were bled until aortic systolic pressure dropped to approximately 50% (64.8 +/- 1.6 mmHg, n = 25) of its control value (136.7 +/- 4.4 mmHg, n = 25), and the hypotension was maintained for 5 min. In control dogs (n = 10), hemorrhage markedly increased aortic epinephrine and hepatic venous norepinephrine. Similarly, aortic IRG, hepatic venous glucose and aortic glucose rose significantly during hemorrhage. In dogs with HNX combined with ADRX (n = 10), aortic epinephrine and hepatic venous norepinephrine remained unchanged during hemorrhage. Aortic IRG concentration, however, increased to a level similar to that observed in the control group. Aortic glucose increased significantly along with significant increases in hepatic venous glucose. In dogs with PCX combined with HNX and ADRX (n = 5), the increases in aortic IRG, hepatic venous glucose and aortic glucose observed in the first two groups in response to hemorrhage were virtually abolished. The results indicate that the increase in aortic IRG during hemorrhage is of pancreatic origin. We conclude that the pancreatic glucagon may be involved in the hyperglycemic response to hemorrhage, most likely through glucose mobilization by the liver during the early phase of hemorrhagic hypotension.     

Sympathoadrenal function in patients with paroxysmal hypertension: pseudopheochromocytoma

OBJECTIVES: The causes of paroxysmal hypertension in patients in whom pheochromocytoma has been excluded ('pseudopheochromocytoma') usually remain unclear. Blood pressure disturbances and symptoms of catecholamine excess in these patients may reflect activation of the sympathetic nervous and adrenal medullary systems. We therefore examined sympathoadrenal function in patients with pseudopheochromocytoma compared with age-matched control subjects in whom there was no suspicion of pheochromocytoma. METHODS: Plasma catecholamines and hemodynamics were examined in response to intravenous glucagon, yohimbine, and trimethaphan in 11 patients with pseudopheochromocytoma and a comparison group of nine normotensive and five hypertensive volunteers. Adrenomedullary function was also assessed by abdominal F-fluorodopamine positron emission tomography and measurements of plasma metanephrine, the O-methylated metabolite of epinephrine. RESULTS: Compared with controls, patients with pseudopheochromocytoma had normal plasma concentrations of norepinephrine, but 120% higher (P < 0.05) baseline plasma concentrations of epinephrine, 80% higher (P < 0.01) baseline plasma concentrations of metanephrine, and sixfold larger (P < 0.05) increases in plasma epinephrine after glucagon. Adrenal 18F-fluorodopamine-derived radioactivity did not differ between groups. Compared with changes in plasma norepinephrine, falls in blood pressure after trimethaphan were 13-fold larger (P < 0.005) and increases in blood pressure after yohimbine were threefold larger (P < 0.01) in pseudopheochromocytoma patients than in controls. CONCLUSION: Patients with pseudopheochromocytoma exhibit a pattern of normal sympathetic noradrenergic outflow, adrenomedullary activation, and augmented blood pressure responses to changes in the sympathoneural release of norepinephrine.     

Impaired modulation of hepatic glucose output overnight after a 72-h fast in normal man

We have previously reported a 25% fall in glucose utilization (Rd) and glucose production (Ra) in normal volunteers during an overnight fast, when glycogenolysis accounts for approximately 70% of hepatic glucose output (HGO). This reduction in Ra and Rd was positively correlated with reductions in glycerol and FFA. To determine if a similar fall in HGO occurs after a prolonged fast when HGO depends solely upon gluconeogenesis, seven normal male volunteers were fasted for 72 h. Glucose kinetics were then assessed overnight using a [3-3H]glucose infusion from 2200-0800 h. Plasma glucose (3.6 +/- 0.1 mM), immunoreactive insulin (2.7 +/- 0.4 mU/L), C-peptide (0.22 +/- 0.03 nmol/l), Rd (1.30 +/- 0.03 mg/kg.min), and Ra (1.28 +/- 0.03 mg/kg.min) were suppressed, and plasma glucagon (98.8 +/- 13.2 pmol/L) was elevated compared to values obtained during the overnight fast, but none of these parameters changed overnight after the 3-day fast. Plasma lactate (0.98 +/- 0.09 mmol/L) and alanine (0.18 +/- 0.03 mmol/L) levels were also unchanged throughout the night. Plasma glycerol (0.14 +/- 0.03 mmol/L) and FFA (0.98 +/- 0.07 mmol/L) were significantly elevated compared to values during the overnight fast, but failed to fall during the study as had been observed during a 14-h fast. We conclude that the modulation of HGO observed during an overnight fast does not occur during prolonged fasting. The lack of nocturnal modulation of HGO when plasma FFA and glycerol levels are fixed at elevated concentrations supports a role of FFA and/or glycerol in the modulation of HGO during an overnight fast.     

Adrenergic influence on glucocounterregulation in man

Summary To investigate the adrenergic role in glucocounterregulatory mechanisms, single-blind randomised studies were performed in 7 normal males during severe insulin-induced hypoglycaemia with or without adrenergic blockade. Intravenous phentolamine administration (5 mg stat and 0.5 mg/ min) did not interfere with the restoration of euglycaemia from hypoglycaemia. However, recovery of blood glucose in the presence of propranolol (3 mg/ 3 min and 0.8 mg/min) was retarded when compared with control studies (mean plasma glucose levels ±SEM, 50±6 mg/dl versus 66±4 mg/dl at 120 min after insulin administration) despite appropriate glucagon, epinephrine, cortisol, and growth hormone responses. Plasma norepinephrine response was unaffected by propranolol but augmented threefold by phentolamine. Increases in plasma lactate, pyruvate and non-esterified fatty acids were blunted with propranolol while rebound non-esterified fatty acid was observed with phentolamine infusion. These data suggest that complete recovery of blood glucose from severe hypoglycaemia requires full sympathetic nervous system activity despite the integrity of other counterregulatory mechanisms.     

Effect of exercise on splanchnic exchange of free fatty acids

Splanchnic exchange of free fatty acids (FFA) was studied in seven healthy male subjects at rest and during bicycle exercise at 700–900 kg-m/min following arterial and hepatic venous catheterization. The arterial-hepatic venous (A-HV) FFA difference correlated significantly with arterial FFA both at rest and during exercise. The regression lines for rest and exercise differed significantly, indicating an increased release of FFA from the extrahepatic splanchnic area during exercise. The A-HV FFA difference did not differ significantly from zero during exercise and correlated negatively to the arterial lactate level. A net release of FFA from the splanchnic area was observed under extreme exercise condition with low FFA levels and arterial lactate above 5 mmole/liter. It is concluded that the net splanchnic FFA uptake is reduced during exercise permitting a redistribution of the body's FFA turnover towards greater FFA utilization by muscle.     

Epinephrine directly antagonizes insulin-mediated activation of glucose uptake and inhibition of free fatty acid release in forearm tissues.

To determine whether the anti-insulin effect of epinephrine is due to a direct antagonism on target tissues or is mediated by indirect mechanisms (systemic substrate and/or hormone changes), insulin and epinephrine were infused intrabrachially in five normal volunteers using the forearm perfusion technique. Insulin (2.5 mU/min) was infused alone for 90 minutes and in combination with epinephrine (25 ng/min) for an additional 90 minutes, so as to increase the local concentrations of these hormones to physiological levels (60 to 75 microU/mL and 200 to 250 pg/mL for insulin and epinephrine, respectively). Systemic plasma glucose and free fatty acids (FFA) concentrations remained stable at their basal values during local hormone infusion. Forearm glucose uptake (FGU) increased in response to insulin alone from 0.8 +/- 0.2 mg.L-1.min-1 to 4.3 +/- 0.8. Addition of epinephrine completely abolished the insulin effect on FGU, which returned to its preinfusion value (0.7 +/- 0.2). Forearm lactate release was slightly increased by insulin alone, but rose markedly on addition of epinephrine (from 5.2 +/- 0.8 mumol.L-1.min-1 to 17 +/- 2; P less than .02). During infusion of insulin alone, forearm FFA release (FFR) decreased significantly from the postabsorptive value of 1.76 +/- 0.25 mumol.L-1.min-1 to 1.05 +/- 0.11 (P less than .01). Epinephrine addition reverted insulin suppression of FFR, which returned to values slightly above baseline (2.06 +/- 0.47 mumol.L-1.min-1; P less than .05 v insulin alone). The data demonstrate that epinephrine is able to antagonize directly insulin action on forearm tissues with respect to both stimulation of glucose uptake and inhibition of FFA mobilization.     

Interactions of insulin and epinephrine in human metabolism: their influence on carbohydrate and lipid oxidation rate.

Two groups of normal male subjects were given an infusion of insulin and an infusion of epinephrine + insulin respectively. Blood glucose, plasma free fatty acids (FFA), insulin, growth hormone, cortisol, and urinary catecholamines were determined. Continuous indirect calorimetry was used to measure metabolic rate and oxidation rates of carbohydrate and lipids. The first group (n equals 7) received a 30-minute insulin infusion (0.1 IU/kg). While blood glucose and plasma FFA decreased, carbohydrate oxidation and metabolic rate significantly increased after some delay, whereas lipid oxidation decreased. The increase in carbohydrate oxidation amounted to 5 g/120 min. The decrease in blood glucose during insulin administration did not correlate with the increase in carbohydrate oxidation. In the second group (n equals 7), a 150-minute epinephrine infusion (900 mug in 500 ml saline) was administered, and superimposed upon it, a similar insulin infusion initiated after 60 min. Epinephrine alone increased blood glucose and plasma FFA levels, and decreased insulinemia. The rise in the metabolic rate was sharp and significant. After a short but significant increase the oxidation rate of carbohydrate decreased, whereas that of lipids markedly rose. This increase significantly correlated with that in FFA. Addition of insulin markedly decreased the elevated FFA levels and lowered blood glucose. After some delay this was followed by a marked increase in carbohydrate oxidation and a decrease in lipid oxidation. In this test the total increase in carbohydrate oxidation was 11 g/120 min. In comparison with the insulin test, this double amount seems to correlate well with the higher blood glucose levels measured before insulin administration. The results suggest that insulin indirectly stimulates carbohydrate oxidation by facilitating glucose transport into the cells and lowering FFA levels, and that epinephrine favours lipid oxidation through its lipolytic effects and its suppression of insulin release.     

The effect of acute glucagon removal on the metabolic response to stress hormone infusion in the conscious dog

The effect of acute glucagon removal on glucose metabolism following long-term (70-hour) stress hormone infusion (day 3) was investigated in 20-hour-fasted conscious dogs. Stress hormone infusion increased arterial plasma glucagon, cortisol, epinephrine, and norepinephrine (∼ fivefold), as well as arterial plasma glucose (Δ82 ± 16 mg/dL) and insulin (Δ26 ± 5 μU/mL). After assessing basal glucose metabolism on day 3, the long-term glucagon infusion was discontinued (n = 6), and the remaining hormones were infused for an additional 180 minutes. Constant glycemia was maintained by an exogenous glucose infusion. In five dogs, the stress hormone infusion containing glucagon was continued for 180 minutes. Glucose production and gluconeogenesis were assessed using tracer and arteriovenous-difference techniques. Acute removal of glucagon decreased arterial plasma glucagon from 220 ± 24 to 32 ± 4 pg/mL and net hepatic glucose output (Δ1.6 ± 0.3 mg/kg/min). Net hepatic handling of lactate, alanine, and glycerol was not altered. The efficiency of gluconeogenesis, on the other hand, was decreased by 40%. Liver biopsies taken following discontinuation of glucagon indicated that both³H- and¹⁴C-glucose accumulated in glycogen. The calculated rate of plasma glucose and gluconeogenic precursor diversion to glycogen increased by fivefold and fourfold, respectively. The increased gluconeogenic precursor diversion to glycogen accounted for 58% of the decrease in the efficiency of gluconeogenesis. In conclusion, acute removal of glucagon during stress hormone infusion decreased net hepatic glycogenolysis in the face of prevailing hyperglycemia and hyperinsulinemia, while having minimal effects on the gluconeogenic process per se.     

Metabolic and endocrine responses to a standard mixed meal. A physiologic study

Summary In order to study endocrine and metabolic responses to normal food ingestion, 8 ‘healthy’ subjects received a standard mixed meal which reflected the composition of Western diet (CHO 47%, protein 23%, fat 26%, alcohol 4%), in 20 min. Before and after the meal, in each subject glucose, lactate, FFA, insulin, C-peptide, glucagon and HGH were determined. The results showed that glycemic and insulinemic responses were not very different from those observed after the classical oral glucose tolerance test. Plasma FFA and blood lactate decreased progressively after the meal. Plasma glucagon and HGH showed opposite changes: pancreatic glucagon rose and HGH slightly declined after composite food ingestion. Supported by C.N.R. grant No. 76.01321.04 115.1187.     

Comparative assessment of stimuli that release neuronal and adrenomedullary catecholamines in man.

We assessed the release of neuronal and adrenomedullary catecholamines in response to various stimuli of the sympathetic nervous system in normal subjects. Plasma catecholamines and their urinary metabolites, normetanephrine and metanephrine, were measured. Sodium restriction increased supine plasma norepinephrine by 37% and ambulatory plasma norepinephrine by 22%, with urinary normetanephrine excretion increased 29%. The sodium restriction did not elevate plasma epinephrine or urinary metanephrine. The most potent stimuli of norepinephrine were treadmill exercise, orthostasis, caffeine, the cold pressor test, sodium restriction and handgrip exercise, in descending order. Plasma epinephrine was increased by caffeine, treadmill exercise, the cold pressor test, handgrip exercise and the Valsalva maneuver, in that order. Syncope resulted in profound changes in plasma epinephrine but only modest changes in plasma norepinephrine. We conclude that in man, there is frequent dissociation between the effects of different stimuli on neuronal and adrenomedullary catecholamine release.     

Impaired plasma catecholamine response to submaximal treadmill exercise in obese women

After an overnight fast, blood samples were obtained from seven obese women (50% +/- 3% body fat) and from seven control women (25% +/- 1% body fat) before, during, and after 10 minutes of treadmill exercise at 70% of each individual's maximal oxygen uptake (VO2max). During exercise, peak plasma epinephrine (E), norepinephrine (NE), and glucagon concentrations in the control group significantly exceeded corresponding peak values in the obese group by 1.4-fold to twofold, whereas lactate responses did not differ. After 5 minutes of rest, peak plasma glucose, free fatty acid (FFA), and growth hormone (GH) concentrations in the control group also were significantly higher than in the obese women, but the plasma cortisol responses were comparable. Although plasma insulin concentrations decreased during exercise and rose to maximum values at 5-minute recovery in all individuals, levels were more than 3.5-fold higher in the obese group throughout the study. We conclude that the combination of heightened plasma insulin and diminished catecholamine and other counterregulatory hormone responses may account for subnormal plasma substrate increments that distinguish obese from non-obese women during exercise at comparable work intensities.