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Biomedical subjects

H Shamoon

Publications and source records attributed to H Shamoon.

At least 55 records · Page 3Linked to original sources
PubMed1989

Regulation of counterregulatory hormone secretion in man during exercise and hypoglycemia.

We examined the role of the plasma glucose concentration per se in the secretion of counterregulatory hormones during exercise. Ten men (average age, 24 yr; maximal aerobic capacity, 31.8 mL/kg.min) were studied during two 50-min bicycle exercise periods at either normal glucose [87 +/- 1 (+/- SE) mg/dL (4.8 +/- 0.1 mmol/L)] or low glucose [59 +/- 1 mg/dL (3.3 +/- 0.1 mmol/L)]. The plasma glucose targets were achieved by exogenous insulin and variable glucose infusions. These results were compared to studies in which saline was infused. Exercise at normal glucose was associated with significant increments in plasma epinephrine (maximum 3- to 5-fold above baseline) and norepinephrine (2-fold), comparable to those that occurred during saline administration. Plasma GH increased only at the most intense exercise level, while plasma cortisol and glucagon did not increase significantly. In low glucose-exercise studies, the increase in plasma epinephrine during exercise was significantly greater than that at normal glucose (P less than 0.01), although proportional to basal preexercise levels (r = 0.73; P less than 0.001). Plasma glucagon increased almost 100%, and plasma cortisol and GH increased by 150% and 400%, respectively. Compared to the effect of the same degree of hypoglycemia in the absence of exercise, only plasma epinephrine (P = 0.002) and norepinephrine (P less than 0.001) displayed effects independent of hypoglycemia during exercise. When low glucose was reversed to normal at the midpoint of exercise, plasma epinephrine and glucagon returned to the levels obtained for the same duration of exercise at normal glucose, while norepinephrine, GH, and cortisol were only partially responsive to the rise in plasma glucose. These data suggest that 1) moderate exercise is a stimulus for a sympathoadrenal and GH response, but not a peripheral glucagon response; 2) during exercise and hypoglycemia, plasma epinephrine and norepinephrine are enhanced, while the glucagon response is entirely glucose dependent; and 3) the epinephrine response to hypoglycemia can be dissociated from that to exercise, suggesting differing control mechanisms. We conclude that the activation of counterregulatory hormones during exercise is regulated by glucose-independent mechanisms, although these responses may be augmented by concurrent hypoglycemia.

Adult↗
PubMed1988

Hormonal and metabolic effects of calcium channel antagonists in man.

Calcium is a component of many metabolic reactions. By blocking calcium transport across cell membranes, calcium channel antagonists can therefore theoretically affect numerous metabolic and hormonal processes. In vitro studies have often documented just such an effect. Because of the expanding use and prevalence of calcium antagonists in clinical practice, a review of their in vivo effects on hormones and metabolism is warranted. The effect on glucoregulatory hormones, calcium regulatory hormones, anterior and posterior pituitary secretion, the renin-angiotensin axis, plasma catecholamines, and plasma lipids and lipoproteins is herein reviewed. The various calcium antagonists, by virtue of their distinct chemical structures, influence metabolism in their own unique manner. Despite the widespread involvement of calcium in hormone action, however, calcium channel antagonists have little dramatic impact on hormone regulation. This is, in part, due to the drug dosage used in clinical practice and to the inherent compensatory mechanisms built into normal endocrine function. The development of agents with greater and more potent metabolic specificity, however, coupled with the ability to target drug action, holds promise for expanded therapeutic application in the future.

Adrenal Cortex Hormones↗
PubMed1987

Defective epinephrine and growth hormone responses in type I diabetes are stimulus specific.

The counterregulatory hormone responses to hypoglycemia and a non-glucose stimulus, exercise, were evaluated in 18 subjects with type I diabetes and in 9 normal controls. Subjects with diabetes had no overt neuropathy, with R-R variations and postural plasma norepinephrine increments that were similar to those of controls. The diabetic subjects exhibited normal increments in plasma growth hormone (GH), norepinephrine, and cortisol but blunted or absent responses in plasma epinephrine and glucagon when hypoglycemia was severe (less than 40 mg/dl). During a 60-min clamped reduction in plasma glucose at approximately 65 mg/dl, plasma GH and epinephrine increased 6- to 15-fold in controls but 2- to 4-fold in diabetics (P less than .05). However, when subjects were exercised at this plasma glucose level (50 W for 10 min), plasma epinephrine and GH in diabetics rose markedly by 150-400% to attain the peaks reached by the controls. Plasma norepinephrine and cortisol increased to similar levels in both groups, and plasma glucagon was not significantly changed. We conclude that epinephrine and GH secretion in response to hypoglycemia are reduced in type I diabetes but that these defects are stimulus specific because the responses to exercise are not reduced.

Adult↗
PubMed1986

Assessment of long-term glycemia in type I diabetes using multiple blood glucose values stored in a memory-containing reflectometer.

The relationship between repetitive hemoglobin A1 values and daily blood glucose tests performed by 20 insulin-dependent diabetic outpatients was assessed over a six-week period using a modified reflectance meter capable of storing blood glucose determinations automatically. An average of four and a half determinations per subject per day was recorded with a range of average blood glucose values between 82 +/- 2 mg/dl and 316 +/- 5 mg/dl (mean +/- SE). The relationship between average blood glucose and hemoglobin A1 values was significant when hemoglobin A1 values at the end of the six-week period were correlated with the mean blood glucose level over that period (r = 0.55, p less than 0.02), but improved when a more remote hemoglobin A1 value obtained at 10 weeks was used (r = 0.64, p less than 0.005). Hemoglobin A1 values covering two-week intervals were extremely poor in reflecting average glycemia. The average fasting blood glucose level in these subjects was highly correlated with the overall daily blood glucose values (r = 0.89, p less than 0.0001), although the coefficients of variation of these parameters averaged 43 +/- 3 percent and 47 +/- 2 percent, respectively, and were greater than that of the hemoglobin A1 values over six weeks (10 +/- 2 percent). It is concluded that labile blood glucose control in patients with insulin-dependent diabetes is accurately reflected by the average fasting blood glucose level, although multiple determinations must be employed. Satisfactory assessment may be made by use of hemoglobin A1 value provided that the hemoglobin A1 determination follows a sufficiently long period of time, presumably related to the turnover of glycosylated hemoglobin.

Blood Glucose↗
PubMed1986

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

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.

Adult↗
PubMed1985

Influence of oral verapamil on glucoregulatory hormones in man.

We evaluated the effect of treatment with placebo or verapamil (320 mg/day) for 2 weeks on glucose-induced insulin secretion and hypoglycemia-stimulated counterregulatory hormone secretion in hypertensive patients. Verapamil treatment was associated with a significant reduction in diastolic blood pressure (P = 0.02 vs. placebo). During a hyperglycemic clamp (plasma glucose raised 125 mg/dl above basal level) maintained for 90 min, plasma insulin increased 4- to 5-fold (early) and then to values 8- to 10-fold above baseline (late). These increments were identical during placebo or verapamil treatment. The rates of glucose metabolized during each study also were similar, suggesting that no significant change in insulin action occurred during drug treatment. When plasma glucose was allowed to decline precipitously from hyperglycemic levels (220 mg/dl) to nadirs ranging from 42-77 mg/dl, plasma concentrations of glucagon, cortisol, epinephrine, and norepinephrine all increased; however, no consistent differences in the counter-regulatory hormone responses could be attributed to verapamil therapy. We conclude that physiologically effective drug concentrations of verapamil capable of influencing blood pressure do not have a significant effect on secretion of glucoregulatory hormones in man.

Adult↗
PubMed1985

Rest and exercise hemodynamic and adrenergic responses to enalapril, hydrochlorothiazide, and combination treatment in patients with systemic hypertension.

The effects of enalapril (10-20 mg twice daily), hydrochlorothiazide (25-50 mg twice daily), and combination enalapril-hydrochlorothiazide therapy (10-20 mg enalapril/25-50 mg hydrochlorothiazide in combination tablet twice daily) were evaluated and compared to no therapy (control) in eight patients with mild to moderate hypertension at rest and during treadmill exercise. All active treatments reduced standing blood pressure in patients at rest compared to the control group (p less than 0.05); however, none produced significant reductions of standing blood pressure in patients at peak exercise. Standing heart rates of patients at rest and at peak exercise were not changed with active therapy. However, standing heart rate in patients at rest was lower with enalapril than with hydrochlorothiazide and combination therapy (p less than 0.05). Heart rate of patients on hydrochlorothiazide was higher than with control and other therapies at Stage I of exercise (p less than 0.01). Supine norepinephrine levels in patients at rest were elevated with both hydrochlorothiazide and combination therapy when compared to that in patients with enalapril and control (p less than 0.05). Treatment with enalapril alone produced no changes in plasma catecholamine levels compared to control. There were no differences between control and all treatment regimens in peak exercise levels of catecholamines. Thus, enalapril, hydrochlorothiazide, and combination therapy, although effective in lowering resting blood pressure, may not be effective in blunting the blood-pressure response to exercise. The drugs do not appear to have any significant effects on catecholamine levels in patients at peak exercise.

Adult↗
PubMed1984

Beta-adrenergic blockade is more effective in suppressing adrenaline-induced glucose production in Type 1 (insulin-dependent) diabetes.

To examine whether diabetes affects the ability of beta-blockade to suppress adrenaline-stimulated hepatic glucose production, we infused adrenaline with and without propranolol into normal subjects and diabetic patients receiving a constant insulin infusion in basal amounts. In normal subjects, propranolol did not block the transient 50%-60% rise in glucose production during adrenaline infusion. In contrast, propranolol virtually abolished adrenaline-induced hyperglycaemia and glucose production was virtually abolished by propranolol in the diabetic patients, even though they demonstrated an exaggerated response to adrenaline alone (persistent increase in glucose production of 50%-90% above baseline). When insulin was infused together with adrenaline and propranolol in normal subjects in doses exceeding those given to the diabetics (plasma insulin rose threefold), the rise in glucose production was still threefold greater than in the diabetic patients (p less than 0.02). We conclude that beta-blockade is more effective in suppressing the hepatic response to adrenaline in diabetics than in normal subjects. Our data may explain why diabetic subjects are more vulnerable to hypoglycaemia during treatment with propranolol.

Adolescent↗
PubMed1984

Reliability of blood glucose monitoring by patients with diabetes mellitus.

Nineteen patients with insulin-dependent diabetes mellitus were evaluated for overall reliability of self-generated data from capillary blood glucose monitoring. For a period of 12 to 14 days, standard reflectance meters used by these subjects were replaced by meters internally modified with memory chips capable of storing all glucose readings by date and time. The subjects were not aware of this modification and were instructed to continue to test capillary blood glucose as they had been and to continue their practice of recording the meter readings in a logbook. To assess reliability of patient-generated data as recorded in the logbook, the addition, deletion, and alteration of test results were determined. A significantly lower (p less than 0.0001) mean blood glucose level was reported in the logbooks than recorded in the memory reflectance meters. Differences in logbooks and memory reflectance meters ranged from 0 to 109 mg/dl. Three fourths of the subjects had reported lower than actual mean blood glucose values. Under-reporting, or omission of memory reflectance meter readings, averaged 10 percent, whereas over-reporting or addition of phantom values averaged 40 percent. An average of 26 percent of the logbook entries were not identical to memory reflectance meter values determined at the corresponding time. Two thirds of the subjects had reported values in such a manner as to obscure hyper- and hypoglycemia, leading to misleading clinical impressions about the fluctuation in metabolic control. Previous glycemic control, patterns of logbook recording, or visits to the clinic were not found to be predictive of the reliability of patient self-monitoring regimens.

Adolescent↗
PubMed1983

Impaired counterregulation of hypoglycemia in insulin-dependent diabetes mellitus.

We evaluated the recovery of blood glucose after insulin-induced hypoglycemia in six insulin-dependent diabetics (insulin-infused and initially euglycemic) and six normal controls after comparable reductions in plasma glucose. In contrast to controls, the recovery of plasma glucose was delayed in diabetics (2-h plasma glucose 80 +/- 5 mg/dl and 58 +/- 5 mg/dl, respectively, P less than 0.01). This delay was due to the absence of a rebound in hepatic glucose output in the diabetics, whereas glucose output rose two- to threefold above baseline in normals. The impaired rebound in glucose output in diabetics could not be attributed to hyperinsulinemia. Rather, hypoglycemia-induced secretion of epinephrine and glucagon was reduced in the diabetics by 60-80% as compared with normals (P less than 0.001). The diabetics did not suffer from overt neuropathy and plasma cortisol, growth hormone, and norepinephrine increased normally following hypoglycemia. The data suggest that prolonged hypoglycemia may frequently occur in tightly controlled type I diabetics because of impaired rebound in hepatic glucose release which in turn may be a consequence of reduced secretion of epinephrine and glucagon.

Adult↗
PubMed1982

Comparative effects of abrupt withdrawal of propranolol and verapamil in angina pectoris.

The potential hazards of abrupt withdrawal of propranolol have been described in patients with angina pectoris; however, the effects of abrupt withdrawal from long-term therapy with verapamil have not previously been investigated. The comparative effects of withdrawal from long-term treatment with propranolol and verapamil were assessed in a placebo-controlled double-blind randomized crossover study of 20 patients received placebo for 2 weeks, then increasing doses of propranolol (60 to 320 mg/day) or verapamil (240 to 480 mg/day) for 3 weeks. Patients were then abruptly withdrawn from drug onto placebo for 1 week, followed by crossover to the other drug treatment and a second withdrawal period. All 20 patients were withdrawn from verapamil without evidence of a rebound increase in frequency of anginal attacks, blood pressure, heart rate, or rate-pressure product and without a rebound deterioration in exercise tolerance. In contrast, with propranolol withdrawal, 2 patients (with the highest baseline angina attack rate) had a severe exacerbation of their anginal syndrome and could not undergo formal exercise testing; the other 18 patients were withdrawn from propranolol without incident. Plasma catecholamines were increased during exercise compared with rest during all treatments; however, the levels of catecholamines during exercise were significantly higher with propranolol than with verapamil and placebo (p less than 0.05). Levels of exercise catecholamines returned to placebo baseline values after withdrawal of propranolol.

Angina Pectoris↗
PubMed1982

Selective counterregulatory hormone responses after oral glucose in man.

The plasma response of various counterregulatory hormones was measured after an oral glucose tolerance test in 19 normal subjects. Significant elevations in plasma epinephrine (P less than 0.05) and human GH (P less than 0.05) were observed late in the course of the oral glucose tolerance test coincident with the fall in plasma glucose. Plasma norepinephrine, glucagon, and cortisol levels did not change during the latter phase of the test. The elevations in plasma human GH and epinephrine levels were unrelated to either absolute hypoglycemia or to clinical symptoms of hypoglycemia. These data suggest a possible role for adrenergic mechanisms in glucose counterregulation under physiological conditions.

Adult↗
PubMed1981

Synergistic interactions among antiinsulin hormones in the pathogenesis of stress hyperglycemia in humans.

We infused epinephrine, glucagon, and cortisol in combination into health overnight-fasted subjects in doses designed to simulate changes in severe stress. When all three hormones were infused simultaneously, glucose levels rose above 200 mg/dl in spite of a 100-200% increase in plasma insulin. In contrast, infusion of each hormone individually produced either a mild (less than 120 mg/dl) or a transient elevation in the plasma glucose concentration. With the combined hormone infusion, the increment in plasma glucose was 3-fold greater than the sum of the responses to the individual hormones (P less than 0.001). The marked hyperglycemia in this setting is a result of ongoing glucose overproduction which is stimulated by epinephrine and glucagon and sustained by cortisol. Furthermore, epinephrine (and possibly cortisol) inhibited glucose disposal despite concomitant hyperinsulinemia. In contrast to their effects on glucose regulation, the simultaneous infusion of epinephrine, glucagon, and cortisol failed to cause hyperketonemia. We conclude that the combined infusion of epinephrine, glucagon, and cortisol produces a greater than additive hyperglycemic response in normal humans. These data suggest that the clinical occurrence of fasting hyperglycemia in a setting of hypersecretion of multiple antiinsulin hormones (stress hyperglycemia) may result, at least in part, from synergistic interactions among these hormones.

Adult↗
PubMed1980

Epinephrine and the regulation of glucose metabolism: effect of diabetes and hormonal interactions.

Elevations of plasma epinephrine comparable to those observed in physiologic stress, cause a sustained 20--35 mg/dl elevation of plasma glucose in normal humans. This hyperglycemic action is due to a transient increase in hepatic glucose output as well as a reduction in the rate of glucose disposal which accounts for the persistence of hyperglycemia. The latter results from epinephrine-induced suppression of endogenous insulin secretion and, more importantly from a direct inhibitory effect on insulin-stimulated glucose utilization. In diabetes, the hyperglycemic effect of epinephrine is markedly accentuated. The enhanced rise in plasma glucose is due to an alternation in response of the liver to epinephrine. Despite infusion of insulin, epinephrine produces a sustained rather than transient elevation in hepatic glucose output in diabetic subjects. In contrast, the inhibitory effect of epinephrine on glucose utilization is unchanged by the diabetic state. In normal subjects, the hyperglycemic action of epinephrine is enhanced by simultaneous elevations of glucagon and cortisol. The former increases the magnitude, but not the duration, of the rise in hepatic glucose output induced by epinephrine. The latter, converts epinephrine's hepatic action from a transient to a sustained response. Our data thus suggest that marked hyperglycemia in normal subjects requires the concomitant elevation of multiple anti-insulin hormones, whereas such changes may occur in diabetes if any member of this group of hormones is increased. These findings may account for long-standing clinical observation that stress adversely affects blood glucose regulation to a much greater extent in diabetics as compared to normal subjects.

Adult↗
PubMed1980

Effects of physiological infusion of epinephrine in normal humans: relationship between the metabolic response and beta-adrenergic binding.

In normal humans, infusion of epinephrine for 4 h increased plasma epinephrine to 411 +/- 38 pg/ml but had no significant effect on palsma insulin or glucagon levels. Epinephrine produced a prompt 45% rise in glucose output (P less than 0.01) and a 120% rise in FFA (P less than 0.001), both of which declined to basal levels by 60-90 min. Glucose clearance decreased by 25% (P less than 0.005) and remained suppressed for 4 h. The binding of [125I]hydroxybenzylpindolol to lymphocytes was unchanged after epinephrine infusion. We conclude that in normal humans 1) physiological increments in epinephrine have a persistent effect in decreasing glucose clearance but only transiently increase hepatic glucose output and FFA levels and 2) this refractoriness of liver and adipose tissue to epinephrine occurs without a concomitant decrease in beta-adrenergic binding to lymphocytes.

Adult↗
PubMed1980

The influence of acute physiological increments of cortisol on fuel metabolism and insulin binding to monocytes in normal humans.

The role of physiological hypercortisolemia in the regulation of fuel metabolism in man was examined during a 5-h primed-continuous infusion of cortisol which raised plasma cortisol levels to 40 microgram/dl. Plasma glucose increased by 15--20 mg/dl (P less than 0.005) in spite of unchanged rates of glucose production. Glucose uptake and clearance, on the other hand, fell by 15% (P less than 0.05) and 30% (P less than 0.005), respectively, thereby accounting for cortisol-induced hyperglycemia. Total blood ketones during cortisol infusion increased 3-fold above saline control values (P less than 0.01) despite comparable FFA levels in the two groups. In addition, there was a selective 40% rise in total branched chain amino acids (P less than 0.005) during cortisol infusion. These effects of cortisol on glucose, ketone, and amino acid metabolism occurred in the absence of significant changes in the plasma insulin or glucagon concentration. Furthermore, cortisol infusion had no effect on [125I]insulin binding to circulating monocytes. Our data thus suggest that acute elevations of plasma cortisol have antiinsulin effects in man which may occur independent of alterations in insulin receptors.

Adult↗
PubMed1980

Epinephrine-induced hypoaminoacidemia in normal and diabetic human subjects: effect of beta blockade.

To evaluate the effect of epinephrine on the circulating amino acids, we infused epinephrine into normal human subjects and juvenile-onset diabetic patients given a constant basal infusion of insulin. Epinephrine infusion produced an identical 350--400 pg/ml rise in plasma epinephrine in both groups. In normal subjects, epinephrine caused a progressive 26% reduction in total circulating amino acids, despite unchanged levels of plasma insulin. This effect was most pronounced for the branched amino acids, which fell by 40% (P < 0.001). Plasma alanine was the only amino acid which failed to decline. Similarly, infusion of epinephrine in the insulin-infused diabetics produced a 23% fall in total amino acids, a 37% decline in branched chain amino acids, but no change in plasma alanine. Saline infusion in the insulin-infused diabetics had no effect on plasma amino acid concentrations. In addition, when epinephrine was infused into two insulin-withdrawn diabetics, a comparable hypoaminoacidemic response was observed. The infusion of propranolol in both normal and diabetic subjects totally prevented the epinephrine-induced fall in plasma amino acids. It is concluded that (1) increments in epinephrine similar to those observed in stress cause a decline in circulating amino acids (except alanine) which is greatest for the branched chain amino acids; (2) this hypoaminoacidemic effect occurs in the absence of a rise in plasma insulin and diabetic subjects, as well; and (3) epinephrine-induced changes in amino acid regulation are prevented by beta-adrenergic blockade. Our findings suggest that, in contrast with glucose and fat metabolism, epinephrine and insulin may have similar, rather than antagonistic, effects on plasma amino acid metabolism.

Adult↗