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Biomedical subjects

M A Pfeifer

Publications and source records attributed to M A Pfeifer.

At least 55 records · Page 3Linked to original sources
PubMed1985

Hemodynamic effects of epinephrine: concentration-effect study in humans.

The hemodynamic effects of three different infusion rates of epinephrine (25, 50, or 100 ng X kg-1 X min-1 for 14 min) were examined in 10 normal human subjects. Ejection fraction and changes in cardiac volumes were assessed by radionuclide ventriculography. Plasma epinephrine was increased to levels that spanned the normal physiological range (178 +/- 15, 259 +/- 24, and 484 +/- 69 pg/ml, respectively). Epinephrine infusions resulted in dose-dependent increases in heart rate (8 +/- 3, 12 +/- 2, and 17 +/- 1 beats/min, mean +/- SE) and systolic pressure (8 +/- 1, 18 +/- 2, and 30 +/- 6 mmHg). Although epinephrine infusions had minimal effects on end-diastolic volume, there were significant increases in stroke volume (+26 +/- 2, 31 +/- 4, and 40 +/- 4%), ejection fraction (+0.10 +/- 0.01, 0.14 +/- 0.02 and 0.16 +/- 0.03 ejection fraction units), and cardiac output (+41 +/- 4, 58 +/- 5, and 74 +/- 1%). These increases in left ventricular performance were associated with a decreased systemic vascular resistance (-31 +/- 3, -42 +/- 2, and -48 +/- 8%). Supine bicycle exercise resulted in similar plasma epinephrine levels (417 +/- 109 pg/ml) and similar changes in stroke volume, ejection fraction, and systemic vascular resistance but greater increases in heart rate and systolic blood pressure. Since infusion-associated hemodynamic changes occurred at plasma epinephrine levels commonly achieved during many types of physical and emotional stress, epinephrine release may have an important role in regulating systemic vascular resistance, stroke volume, and ejection fraction responses to stress in man.

Adult↗
PubMed1984

Lack of a direct alpha-adrenergic effect of epinephrine on glucose production in human subjects.

To determine whether alpha-adrenergic stimulation can directly increase glucose production in humans, we infused epinephrine plus propranolol in six normal subjects. The contribution of pancreatic islet effects was eliminated by the infusion of somatostatin. Despite high levels of epinephrine (1,234 +/- 255 pg/ml; mean +/- SE), plasma glucose fell from 85 + 1 to 71 +/- 7 mg/dl. Glucose production rate fell from 1.88 +/- 0.06 to 1.50 +/- 0.16 mg X kg-1 X min-1. During control studies in the same subjects (propranolol and somatostatin without epinephrine), plasma glucose fell from 87 +/- 1 to 75 +/- 3 mg/dl and glucose production fell from 1.93 +/- 0.10 to 1.58 +/- 0.13 mg X kg-1 X min-1. Thus, under conditions of suppressed insulin and falling glucose levels, both of which favor a positive response, a high level of alpha-adrenergic stimulation failed to directly increase glucose production. To ensure that the liver was not refractory to other stimuli, glucagon was administered during infusion of epinephrine and propranolol. In these studies, plasma glucose rose to 175 +/- 20 mg/dl and glucose production plateaued at 3.71 +/- 0.30 mg X kg-1 X min-1 (n = 7). These findings were similar to the effects of propranolol, somatostatin, and glucagon without epinephrine on plasma glucose (196 +/- 15 mg/dl) and glucose production (3.65 +/- 0.29 mg X kg-1 X min-1). Thus, although the liver remained responsive to glucagon during alpha-adrenergic stimulation, no alpha-adrenergic augmentation of glucose production was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Dexamethasone-induced insulin resistance enhances B cell responsiveness to glucose level in normal men.

To determine whether islet adaptation during insulin resistance involves increased responsiveness to the level of plasma glucose, insulin resistance was induced in nine normal men by giving dexamethasone (Dex) (3 mg twice daily for 2 days). Plasma insulin and acute insulin responses (AIR) to isoproterenol were measured at three different glucose levels under control and Dex conditions. During Dex there were elevations above control levels of basal glucose (104 +/- 2 vs. 94 +/- 3 mg/dl) and insulin (21 +/- 3 vs. 13 +/- 2 microU/ml, both P less than 0.03). When glucose levels were raised stepwise by matching amounts using glucose clamps, AIR to isoproterenol rose as a linear function of glucose level under both conditions but rose more steeply during Dex. That is, the potentiating effect of glucose (delta AIR/delta glucose) was greater during Dex: 1.3 +/- 0.2 vs. 0.8 +/- 0.2 (P less than 0.01). Similarly, matched increments in glucose level produced greater increments in prestimulus insulin level during Dex (P less than 0.03). We conclude that 48 h of Dex raises the "gain" of the potentiating effect of glucose. Because the direct effect of glucocorticoids on B cell function has been reported to be inhibitory, the observed stimulation is likely to be a result of the insulin resistance caused by Dex.

Adaptation, Physiological↗
PubMed1984

Variations in circulating catecholamines fail to alter human platelet alpha-2-adrenergic receptor number or affinity for [3H]yohimbine or [3H]dihydroergocryptine.

A series of studies were performed to determine the relationship between physiologic levels of circulating plasma norepinephrine and epinephrine and human platelet alpha-2 binding site number and the affinity (KD) of these sites for antagonist radioligands. In one study, alpha-2-adrenergic binding site number and affinity were compared using both [3H]yohimbine and [3H]dihydroergocryptine as radioligands. There was good absolute and relative comparison for binding site number, but only a relative relationship for KD. In 46 normal subjects, there was no significant relationship between site number or KD and age, plasma epinephrine, or plasma norepinephrine concentration. Even after plasma epinephrine was raised nearly 20-fold by means of an intravenous infusion for 4 h in seven normal subjects, neither sites (608 +/- 68 vs. 567 +/- 120 sites/platelet) nor KD (2.01 +/- 0.94 vs. 2.14 +/- 1.15 nM) were significantly changed. Similarly, neither sites (445 +/- 55 vs. 421 +/- 53 sites/platelet) nor KD (1.44 +/- 0.29 vs. 2.10 +/- 0.75 nM) were significantly changed in six normal subjects when plasma norepinephrine levels increased during oral administration of prazosin for 1 wk. Thus, in a cross-sectional analysis and after a change in plasma catecholamine concentrations, there was no relationship in normal subjects between platelet alpha-2 binding site number or affinity of these sites for antagonist radioligands and the circulating catecholamine levels to which the platelets were exposed. In a group (n = 7) of patients who lack epinephrine-induced platelet aggregation due to abnormal thrombopoiesis, binding site number was decreased (304 +/- 36 vs. 572 +/- 29 sites/platelet, P less than 0.001) and KD tended to be greater (8.69 +/- 2.44 vs. 5.40 +/- 0.31 nM, P = NS) than in normal subjects (n = 46), despite having similar plasma catecholamine levels. There was no difference in binding site number (491 +/- 116 sites/platelet) and KD (5.61 +/- 0.84 nM) in patients (n = 5) with autonomic insufficiency and low levels of upright plasma norepinephrine when compared with the normal subjects. Two patients were examined before and after the removal of a pheochromocytoma. Their binding site number and KD were normal before the operation and essentially unchanged after the tumor removal and fall of plasma catecholamines. Thus, this study demonstrates that within the physiologic and pathophysiologic range of plasma catecholamines (in men), there is no relationship between the circulating catecholamine concentration and either platelet alpha-2 adrenergic binding site number or the affinity of these sites for antagonist radioligands.

Adult↗
PubMed1984

An improved method for measuring heart-rate variability: assessment of cardiac autonomic function.

Heart rate oscillates in synchrony with respiration. Several methods have been employed to assess this 'sinus arrhythmia', as an index of autonomic nervous system function. This paper proposes a new, easily computed measure, R, which is relatively resistant to the major nonrespiratory sources of variation, including premature beats, heart-rate differences among subjects, and slow trends in heart rate over time within subjects. The method can also be used more generally in any context where individuals are associated with event processes (for example, with seizures), when one requires assessment of the extent to which a point process is periodic with a particular known period.

Arrhythmia, Sinus↗
PubMed1984

Plasma catecholamines and hemodynamic responses to stress states in man.

The relationship between the plasma catecholamine and hemodynamic responses to stress in man was studied using radionuclide left ventricular angiography to assess changes in cardiac volumes. In 10 healthy men, the maximum plasma norepinephrine (NE) and epinephrine (EPI) responses to symptom-limited supine bicycle exercise were considerably greater than the responses to isometric handgrip exercise or to a cold pressor test. Similarly, increases in heart rate, systolic blood pressure, stroke volume, ejection fraction, and cardiac output were greatest with bicycle exercise. Both the plasma catecholamine and hemodynamic responses to handgrip exercise tended to be intermediate, and the smallest responses were observed during cold pressure testing. The plasma NE and EPI responses to symptom-limited upright treadmill exercise in another group of 10 men were greater than the responses to supine bicycle exercise. During bicycle exercise and during handgrip exercise there were significant correlations between plasma NE and EPI levels and changes of heart rate, blood pressure, and cardiac output. In addition, when data from all three stresses were combined and effects of heart rate and subject differences were controlled for, plasma NE and EPI levels were significantly correlated with ejection fraction. These findings suggest that release of EPI and NE during stress states may contribute to some of the hemodynamic responses that occur during stress.

Adult↗
PubMed1983

Aldose reductase inhibition improves nerve conduction velocity in diabetic patients.

To assess the potential role of polyol-pathway activity in diabetic neuropathy, we measured the effects of sorbinil--a potent inhibitor of the key polyol-pathway enzyme aldose reductase--on nerve conduction velocity in 39 stable diabetics in a randomized, double-blind, cross-over trial. During nine weeks of treatment with sorbinil (250 mg per day), nerve conduction velocity was greater than during a nine-week placebo period for all three nerves tested: the peroneal motor nerve (mean increase [+/- S.E.M.], 0.70 +/- 0.24 m per second, P less than 0.008), the median motor nerve (mean increase, 0.66 +/- 0.27, P less than 0.005), and the median sensory nerve (mean increase, 1.16 +/- 0.50, P less than 0.035). Conduction velocity for all three nerves declined significantly within three weeks after cessation of the drug. These effects of sorbinil were not related to glycemic control, which was constant during the study. Although the effect of sorbinil in improving nerve conduction velocity in diabetics was small, the findings suggest that polyol-pathway activity contributes to slowed nerve conduction in diabetics. The clinical applicability of these observations remains to be determined, but they encourage further exploration of this approach to the treatment or prevention of diabetic neuropathy.

Adult↗
PubMed1983

Differential changes of autonomic nervous system function with age in man.

To assess the relationship between aging and autonomic nervous system function, cardiovascular and pupillary autonomic nervous system reflexes were measured in subgroups of 103 normal male subjects ranging in age from 19 to 82 years (mean age = 39 years). Both the plasma norepinephrine level, a measure of cardiovascular sympathetic nervous system activity, and the mean arterial blood pressure increased with age (r = 0.68 and 0.67, respectively, both p less than 0.001). In contrast, the plasma epinephrine level, a measure of adrenomedullary sympathetic nervous system activity, was unrelated to age (r = 0.08, p = NS). Respiratory variation of heart rate during beta-adrenergic blockade, an index of cardiac parasympathetic nervous system activity, was reduced in older subjects (r = -0.54, p less than 0.001). Thus, there was evidence of an age-related increase of cardiovascular sympathetic nervous system activity and a reduction of cardiac parasympathetic nervous system activity. These findings are consistent with the hypothesis that there is sympathetic nervous system and parasympathetic nervous system compensation of cardiovascular function in response to an age-related decrease in baroreceptor sensitivity. However, dark-adapted pupil size during parasympathetic nervous system blockade, an index of iris sympathetic nervous system activity, declined with age (r = -0.81, p less than 0.001). The latency time for the pupillary response to a light stimulus, an index of iris parasympathetic nervous system activity, was prolonged in older subjects (r = 0.58, p less than 0.001). Thus, both sympathetic nervous system and parasympathetic nervous system inputs to the iris were diminished in older subjects, findings consistent with the generalized decrease of peripheral somatic nerve function that has been reported with aging in man. It is concluded that autonomic nervous system function also declines with aging, but that other age-related changes such as a decline of baroreceptor sensitivity may lead to compensatory autonomic nervous system response, which could mask underlying functional defects.

Adult↗
PubMed1983

Suppression of glucagon secretion during a tolbutamide infusion in normal and noninsulin-dependent diabetic subjects.

To determine the effect of tolbutamide on glucagon release in noninsulin-dependent diabetic and normal subjects and how plasma glucose levels may modulate this effect, the acute glucagon response (AGR) to a 5-g iv arginine pulse was determined before and during a tolbutamide infusion. There was a decrease in plasma glucose concentration in both normal and diabetic subjects (both P less than 0.001); there tended to be a suppression of the AGR (4 of 6 normals and 8 of 11 diabetics), but this suppression was not statistically significant. In separate studies, when the plasma glucose level was clamped at baseline values by a variable rate of glucose infusion, the AGR was suppressed during the tolbutamide infusion in all 7 normal [change in AGR (delta AGR) = -35 +/- 12 pg/ml; P less than 0.05] and all 6 noninsulin-dependent diabetic subjects (delta AGR = -14 +/- 5 pg/ml, p less than .05). In 6 insulin-dependent diabetic subjects, there was no evidence of glucagon suppression by tolbutamide (delta AGR = +2 +/- 2 pg/ml). These results are consistent with the hypothesis that sulfonylureas suppress glucagon secretion by augmenting insulin secretion, an effect that falling glucose levels can mask. Consideration of this observation is necessary when interpreting the effects of a sulfonylurea on islet cell responses.

Adult↗
PubMed1983

Modulation of arginine-induced glucagon release by epinephrine and glucose levels in man.

To assess how physiological epinephrine (EPI) elevations and EPI-induced hyperglycemia interact in the regulation of glucagon secretion, we measured acute glucagon responses (AGR) to arginine at controlled glucose levels during EPI infusions in man. With glucose levels matched at 166 +/- 5 mg/dl using glucose clamp techniques, the AGR (mean change at 2-5 min) to a 5-g iv arginine injection was greater in each subject during the infusion of 15 ng/kg . min EPI (low EPI) than during the control glucose infusion and was still greater during the infusion of 80 ng/kg . min EPI (high EPI; 69 +/- 15, 76 +/- 13, and 142 +/- 22 pg/ml, respectively; n = 8; P less than 0.003). With glucose levels matched at 256 +/- 5 mg/dl, a similar dose-related enhancement of AGR by EPI was seen (control, 53 +/- 12 pg/ml; low EPI, 63 +/- 5 pg/ml; high EPI, 130 +/- 20 pg/ml; P less than 0.008). During control infusions, raising the glucose level from 102 +/- 2 to 166 +/- 5 to 256 +/- 5 mg/dl suppressed AGR from 77 +/- 17 to 69 +/- 15 to 53 +/- 12 pg/ml (P less than 0.002). During low EPI, the same glycemic increments lowered GR from 108 +/- 19 to 76 +/- 13 to 63 +/- 5 pg/ml (P less than 0.02). This suppression of AGR by hyperglycemia was sufficient to obscure stimulation by EPI: at a glucose level of 102 +/- 2 mg/dl during control infusions, AGR was 77 +/- 17 pg/ml, compared to only 76 +/- 13 pg/ml during low EPI with the glucose level higher (166 +/- 5 mg/dl). Multiple linear regression analysis showed a highly significant dependence of AGR on both EPI and glucose levels, accounting for 80% of the within-subject variation in AGR (P less than 0.0001). These data show that 1) EPI is a dose-dependent amplifier of arginine-induced glucagon secretion in man, and 2) hyperglycemia suppresses arginine-induced glucagon secretion, potentially masking the stimulation caused by EPI. The findings suggest that the feedback effect of hyperglycemia on glucagon secretion may help regulate the level of hyperglycemia resulting from adrenergic stimulation.

Adult↗
PubMed1983

The response of plasma triglyceride, cholesterol, and lipoprotein lipase to treatment in non-insulin-dependent diabetic subjects without familial hypertriglyceridemia.

The effects of treatment on plasma total triglyceride, total cholesterol, and plasma postheparin lipase activities have not been evaluated in non-insulin-dependent diabetic (NIDD) subjects without a coexisting familial lipid disorder. In 49 untreated NIDD subjects, there was a linear relationship between glycosylated hemoglobin (GHb) and triglyceride (r = 0.35, P less than 0.02). This correlation was improved after adjusting for the effects of obesity by a partial correlation analysis. After therapy, there was a significant relationship between the change in GHb and the change in triglyceride. To determine whether changes in lipid removal from plasma may contribute to the decrease in plasma lipid concentrations during treatment, the plasma postheparin lipoprotein lipase and hepatic lipase activities were evaluated in a subgroup (N = 8) of these NIDD subjects before and after 1 and 3 mo of therapy. Plasma postheparin hepatic lipase activity in the NIDD subjects was not different from that observed in six normal control subjects and did not change during therapy. In contrast, plasma postheparin lipoprotein lipase activity was lower in the untreated NIDD subjects than in the control subjects. Analysis of the two phases (early and late) of the postheparin lipoprotein lipase activity in plasma showed that the abnormal early phase in untreated NIDD corrected to normal values in less than a month, but the late phase was not corrected until the 3-mo measurement. These findings suggest that some NIDD subjects have a defect in heparin releasable lipoprotein lipase activity, which is reversed with improved glycemic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Chronic chlorpropamide therapy of noninsulin-dependent diabetes augments basal and stimulated insulin secretion by increasing islet sensitivity to glucose.

To determine the effect of chronic sulfonylurea therapy on islet function in noninsulin-dependent diabetes mellitus (NIDDM), studies were performed in 18 untreated NIDDM patients before and after 12-16 weeks of chlorpropamide therapy. Fasting plasma glucose (FPG) fell with chlorpropamide therapy from 249 +/- 16 to 157 +/- 8 mg/dl (mean +/- SEM; P less than 0.001), and basal insulin increased from 17 +/- 2 to 24 +/- 3 microU/ml (P less than 0.001). The percent change in basal insulin correlated with the pretreatment FPG (r = 0.62; P less than 0.01) and inversely with the change in FPG during chlorpropamide (r = -0.57; P less than 0.025). Thus, patients with the highest pretreatment FPG showed the largest relative increase in basal insulin and the largest fall of FPG with chlorpropamide therapy. In nine patients, arginine-stimulated acute insulin responses (AIR) were studied at each of three plasma glucose (PG) levels both before and during chlorpropamide treatment. AIR at FPG was not different before and during treatment. However, when PG during treatment was matched by glucose infusion to the pretreatment FPG, the AIR was clearly increased during chlorpropamide therapy (176 +/- 65 vs. 49 +/- 11 microU/ml; P less than 0.02). When AIR is plotted against PG for each individual, the slope of the regression line generated (slope of glucose potentiation) is a measure of that patient's islet sensitivity to glucose. The logarithm of the slope of glucose potentiation correlated inversely with FPG (r = -0.92; P less than 0.001). Chlorpropamide treatment increased the slopes of potentiation from 0.26 +/- 0.11 to 1.47 +/- 0.70 (P less than 0.01). We conclude that chronic chlorpropamide therapy augments both basal and stimulated insulin secretion in NIDDM and that this may be an important mechanism of the drug's hypoglycemic effect. The data support the hypothesis that the hyperglycemia of NIDDM is related to islet insensitivity to glucose and that chlorpropamide treatment improves this impairment.

Aged↗
PubMed1982

Insulin responses to nonglucose stimuli in non-insulin-dependent diabetes mellitus during a tolbutamide infusion.

To determine the effect of tolbutamide on insulin release to nonglucose stimuli in non-insulin-dependent diabetes mellitus and how plasma glucose levels may modulate this effect, the acute insulin response (AIR) to an isoproterenol (12 Micrograms) or an arginine (5 g) i.v. pulse was determined before and during a tolbutamide infusion (7.5 mg/m2/min) in 25 male subjects. During the tolbutamide infusion, there was an increase in the AIR to both isoproterenol (% delta AIR = +49 +/- 21%, N = 11, P less than 0.05) and arginine (% delta AIR = +52 +/- 15%, N = 12, P less than 0.005) and a decrease in plasma glucose (delta plasma glucose for isoproterenol = -24 +/- 6 mg/dl, P less than 0.005; for arginine = -26 +/- 3 mg/dl, P less than 0.001). In separate studies, when the plasma glucose was clamped at baseline values by a variable rate of glucose infusion, there was a greater effect of tolbutamide on AIR when compared with the unclamped tolbutamide studies (isoproterenol: % delta AIR = +132 +/- 25%, P less than 0.025; arginine: % delta AIR = +95 +/- 12%, P less than 0.05). Thus, tolbutamide increases the AIR of nonglucose stimuli, but this augmentation by tolbutamide is blunted by the concomitant decrease in plasma glucose. Consideration of this observation is necessary when interpretating the effects of a sulfonylurea on islet cell responses.

Adult↗
PubMed1982

The effect of chronic sulfonylurea therapy on hepatic glucose production in non-insulin-dependent diabetes.

In 20 patients with untreated non-insulin-dependent diabetes mellitus (NIDDM), there was a positive relationship between fasting plasma glucose (FPG) and glucose production rate, calculated by the isotope dilution technique (r = 0.72, P less than 0.001). This suggests that glucose production rate is an important determinant of FPG in untreated NIDDM. Fifteen patients were also studied during therapy with chlorpropamide for 3-6 mo. During therapy, FPG was lower (133 +/- 9 vs. 216 +/- 20 mg/dl, mean +/- SEM; P less than 0.001), glucose production was lower (59.5 +/- 2.0 vs 77.6 +/- 4.9 mg/m2/min; P less than 0.005), and there was a significant correlation between the fall in glucose production and the fall in FPG (r = 0.59, P less than 0.05). Fasting IRI levels increased in some, but not all, patients during chlorpropamide (untreated 18 +/- 2, treated 21 +/- 2 muU/ml; P= NS). However, there was a significant relationship between the percent rise in IRI and the fall in glucose production during treatment (r = 0.75, P less than 0.001). Patients with a rise in fasting insulin during therapy had a greater fall in glucose production than those whose insulin did not rise (25.4 +/- 8.1 vs. 7.8 +/- 2.4 mg/m2/min; P less than 0.005). When a low-dose insulin infusion was given to approximate the increases of portal venous insulin during therapy, similar falls of glucose production occurred. We conclude that inhibition of endogenous glucose production during chronic chlorpropamide therapy is an important mechanism for the lowering of FPG and that enhanced insulin secretion is the reason for the major part of this inhibition. The small fall in glucose production in those patients whose insulin level did not rise during therapy suggests an additional contribution by some other mechanism.

Adult↗
PubMed1982

Quantitative evaluation of cardiac parasympathetic activity in normal and diabetic man.

Heart rate and RR variation (the standard deviation of the mean RR interval for a 5-min period) were evaluated as measurements of cardiac parasympathetic nervous system activity in fasting supine diabetic (N = 22) and comparable age normal (N = 22) subjects. The rate of breathing did not effect heart rate, but was inversely related to the RR variation (r = 0.89, P less than 0.01). Heart rate was increased (P less than 0.0001) and RR variation decreased (P less than 0.05) during beta-adrenergic stimulation with isoproterenol and during parasympathetic blockade with atropine (both P less than 0.0001). Hence, the cardiac effects of beta-adrenergic stimulation may mimic the effects of diminished parasympathetic function. To evaluate parasympathetic control of RR variation, independently of possible effects of increased sympathetic activities, studies were performed during beta-adrenergic blockade with propranolol. RR variation during propranolol was less both in 14 diabetic subjects without clinical symptoms of autonomic neuropathy (P less than 0.005) and in 8 diabetics with clinical symptoms of autonomic neuropathy (P less than 0.001) when compared with 22 age-comparable normal subjects. The measurement of RR variation was very reproducible with a day-to-day coefficient of variation of 9.7 +/- 2.8% (x +/- SEM) in diabetic subjects with stable hyperglycemia. It is concluded that supine RR variation during a deep respiratory rate and during beta-adrenergic blockade is a sensitive, quantitative, and reproducible method to evaluate parasympathetic nervous activity in normal and diabetic subjects. Furthermore, cardiac parasympathetic activity may be diminished in diabetic subjects before clinical symptoms of autonomic neuropathy are evident.

Adult↗
PubMed1981

The regulation of glucose-induced insulin secretion by pre-stimulus glucose level and tolbutamide in normal man.

The relationship between the pre-stimulus glucose level and immunoreactive insulin responses to a glucose challenge (20-g IV) was studied in normal subjects. When the steady-state pre-stimulus glucose concentration was lowered by a 0.33 mU.kg-1.min-1 insulin infusion or raised by a 900 mg/min glucose infusion, no effect on first phase insulin secretion (mean delta 3-5 min insulin level) was observed. In contrast, the second phase response (10-60 min insulin area after glucose pulse) to intravenous glucose fell during insulin infusion and increased during the glucose infusion. Overall, a linear relationship was found between the change of pre-stimulus glucose or level from the control to that during the insulin or glucose infusion and the change in second phase response (r = 0.65, n = 14, p less than 0.02). The effect of tolbutamide infusion (7 mg.m-2.min-1) when compared with saline control was to increase both first phase (+54 +/- 13 mU/l, n = 8, p less than 0.001, mean +/- SEM) and second phase (+972 +/- 256 mU. min-1.l-1, p less than 0.01) insulin secretion. It is concluded that the first phase response to a glucose pulse is independent of the steady-state pre-stimulus glucose concentration and is directly enhanced by tolbutamide; in contrast, second phase is related to both the steady-state pre-stimulus glucose level and tolbutamide. These findings suggest that changes in basal or pre-stimulus plasma glucose during therapy with sulphonylurea drugs may be expected to influence the second phase insulin responses to glucose challenge.

Adult↗