The Physiological Effects of Insulin-Induced Hypoglycaemia in Man: Responses at Differing Levels of Blood Glucose

1983 ◽  
Vol 65 (3) ◽  
pp. 263-271 ◽  
Author(s):  
E. A. M. Gale ◽  
T. Bennett ◽  
I. A. MacDonald ◽  
J. J. Holst ◽  
J. A. Matthews
Keyword(s):  
Blood Pressure ◽  
Growth Hormone ◽  
Plasma Glucose ◽  
Bolus Injection ◽  
Severe Hypoglycaemia ◽  
Normal Male ◽  
Neural Responses ◽  
Cortisol Responses ◽  
Rate Of Recovery ◽  
Hormone Responses

1. The aim of this study was to describe hormonal, cardiovascular and thermoregulatory responses to insulin-induced hypoglycaemia of differing levels of severity. 2. Five normal male volunteers were rendered hypoglycaemic at intervals of 1 week by intravenous infusions of 3, 4 or 6 units of insulin/h, or by intravenous injection of 0.15 unit/kg body weight. 3. Plasma glucose reached nadir values of 2.08 ±0.10, 1.82 ± 0.21, 1.24 ±0.08 and 0.92 ± 0.06 mmol/l (means ± sem) in the four experiments. Non-esterified fatty acid levels fell equally in all experiments but recovery was more rapid with severe hypoglycaemia. In contrast the rate of recovery of plasma glucose was slower with deeper hypoglycaemia and this appeared unrelated to the counter-regulatory response. 4. Plasma glucagon, adrenaline and prolactin levels increased in proportion to the severity of hypoglycaemia, but peak concentrations of cortisol, growth hormone (somatotropin) and noradrenaline did not vary, suggesting that moderate hypoglycaemia had elicited maximal responses. When the areas under the curves were calculated, the cortisol responses were greater for the 6 units infusion and bolus injection than for the other infusions, and the growth hormone responses were similar for all three infusions but significantly greater with the bolus injection. 5. Increases in heart rate and systolic blood pressure were related to the severity of hypoglycaemia, but changes in diastolic blood pressure and peripheral vascular resistance (assessed from calf and from hand blood flow) were not. 6. Central temperature fell by 0.13 ± 0.06°C, 0.30 ± 0.10°C, 0.65 ± 0.14°C and 1.15 ± 0.30°C (means ± sem) in the four experiments, and the fall in skin temperature had a similar gradation. 7. Many physiological responses to hypoglycaemia are not ‘all-or-none’, but vary according to the intensity of stimulus; some are already maximal at mild degrees of hypoglycaemia. Other changes are more complex, reflecting an interplay between opposing endocrine and neural responses.

A Pilot Study of the Mechanism of Action of Desipramine

1981 ◽  
Vol 138 (3) ◽  
pp. 248-251 ◽  
Author(s):  
S. A. Checkley ◽  
A. P. Slade ◽  
E. Shur ◽  
S. Dawling
Keyword(s):  
Blood Pressure ◽  
Growth Hormone ◽  
Pilot Study ◽  
Mechanism Of Action ◽  
Depressed Patients ◽  
Sedative Effects ◽  
Before And After ◽  
Hormone Responses

SummaryTo test the hypothesis that desipramine alters α adrenoceptor function in depressed patients, the effects of clonidine upon growth hormone sedation and blood pressure have been measured in depressed patients before and after treatment with desipramine. After three weeks of treatment the hypotensive and sedative effects of clonidine were inhibited in all patients even though plasma desipramine concentrations at this time varied from 42 to 560 μg/l. Growth hormone responses to clonidine were enhanced in five of the six patients but this effect was not statistically significant. These findings are consistent with the hypothesis that in these patients desipramine altered α adrenoceptor function: other explanations are discussed.

Effect of adrenaline on basal and ovine corticotrophin-releasing factor-stimulated ACTH secretion in man

1987 ◽  
Vol 112 (1) ◽  
pp. 145-150 ◽  
Author(s):  
S. Al-Damluji ◽  
D. Cunnah ◽  
A. Grossman ◽  
L. Perry ◽  
G. Ross ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Biological Effects ◽  
Random Order ◽  
Normal Male ◽  
Plasma Acth ◽  
Plasma Adrenaline ◽  
Corticotrophin Releasing Factor ◽  
Cortisol Responses ◽  
Male Subjects ◽  
Single Blind

ABSTRACT Six normal male subjects were given, in single blind random order on six separate occasions, i.v. bolus doses of synthetic ovine corticotrophin-releasing factor-41 (oCRF-41; 25 and 50 μg) with and without adrenaline (3 μg/min) i.v. for 150 min, the adrenaline infusions alone and saline placebo. The adrenaline infusions resulted in plasma adrenaline concentrations of 4·33 ± 0·82 (s.e.m.) nmol/l and were associated with an increase in blood glucose, heart rate and systolic blood pressure and a reduction of diastolic blood pressure. Despite these evident biological effects at several sites, there was no stimulation of plasma ACTH or cortisol by adrenaline in comparison with the effect of saline, and no enhancement of the stimulatory effect of either dose of oCRF-41 on ACTH or cortisol secretion. The ACTH response to 50 μg oCRF-41 was greater than that to 25 μg, indicating that the 25 μg dose of oCRF-41 was sub-maximal and capable of further enhancement. As the plasma adrenaline concentrations during the adrenaline infusions reached the upper limit of the physiological range of plasma adrenaline in man, yet failed to enhance the ACTH or cortisol responses to a sub-maximal dose of oCRF-41, we conclude that circulating adrenaline neither exerts a direct stimulatory effect on pituitary corticotrophs nor enhances the effect of CRF under physiological circumstances. The adrenaline infusions attenuated the ACTH and cortisol responses to oCRF-41 and were associated with a transient reduction of basal concentrations of both hormones. J. Endocr. (1987) 112, 145–150

Growth hormone responses to multiple injections of a fragment of human growth hormone-releasing factor in conscious male and female rats

1985 ◽  
Vol 106 (3) ◽  
pp. 281-289 ◽  
Author(s):  
R. G. Clark ◽  
I. C. A. F. Robinson
Keyword(s):  
Growth Hormone ◽  
Human Growth ◽  
Female Rats ◽  
Male Rats ◽  
Normal Male ◽  
Male And Female ◽  
Gh Secretion ◽  
Male And Female Rats ◽  
Hormone Responses ◽  
Males And Females

ABSTRACT The GH responses to single i.v. injections of GH-releasing factor (GRF) in conscious male rats are highly variable. Although normal male rats show a pulsatile secretory pattern of GH with pulses occurring at intervals of 3–3·5 h, the peaks occur at different times in individual animals. We have compared the GH responses of young conscious male and female rats to multiple i.v. injections of 1 μg human (h) GRF1-29NH2. The peak GH responses occurred 3–5 min after hGRF1-29NH2 injection and were lower in female than in male rats. Both males and females responded uniformly to hGRF1-29NH2 injections given 180 min apart and the GH responses became entrained with no endogenous GH pulsing. Female rats produced consistent GH peaks in response to hGRF1-29NH2 injections at 90-min intervals, whereas male rats responded only to alternate injections, so that GH peaks occurred only every 180 min despite giving GRF every 90 min. When the frequency of hGRF1-29NH2 administration was increased to once every 40 min female rats again responded consistently to each injection. Male rats responded intermittently, being able to respond to two injections 40 min apart, after which they became refractory to hGRF1-29NH2. This cycle of varying sensitivity to GRF in male rats probably underlies their 3-hourly endogenous GH secretory rhythm. Female rats can respond uniformly to repeated GRF injections, consistent with their more continuous pattern of endogenous GH secretion. Introducing a pulse of 10 μg rat GH into a series of hGRF1-29NH2 injections did not induce refractoriness to hGRF1-29NH2, suggesting that GH does not itself desensitize the pituitary to GRF. Whether the different patterns of GH secretion in males and females result from different patterns of GRF and/or somatostatin secretion remains to be determined. J. Endocr. (1985) 106, 281–289

Platelet-activating factor-induced increases in glucose kinetics

1988 ◽  
Vol 254 (2) ◽  
pp. E193-E200
Author(s):  
C. H. Lang ◽  
C. Dobrescu ◽  
D. M. Hargrove ◽  
G. J. Bagby ◽  
J. J. Spitzer
Keyword(s):  
Blood Pressure ◽  
Plasma Glucose ◽  
Infusion Rate ◽  
Bolus Injection ◽  
Platelet Activating Factor ◽  
Whole Body ◽  
Constant Infusion ◽  
Adrenergic Blockade ◽  
Glucose Kinetics ◽  
Infusion Period

Platelet-activating factor (PAF) is a postulated mediator of many of the early hemodynamic effects of endotoxin. The aim of the present study was to determine whether in vivo administration of PAF could produce alterations in whole-body glucose metabolism that would mimic those seen during endotoxemia. Glucose kinetics were assessed in chronically catheterized conscious rats by the constant infusion of [6-3H]- and [U-14C]glucose before and for 4 h after either a bolus injection (300 ng/kg) or a constant infusion (20 or 220 ng.min-1.kg-1) of PAF. The bolus injection of PAF produced a 30% decrease in blood pressure by 5 min that returned to control levels by 30 min. Increased plasma glucose (40%) and lactate (150%) levels after injection of PAF were also transient. In contrast, the bolus injection of PAF elevated the rate of glucose appearance (Ra; 44%) for 1.5 h. The lower PAF infusion rate decreased blood pressure 11% to 104 mmHg, whereas the higher infusion rate decreased pressure 34% to 77 mmHg. Both PAF infusion rates produced elevations in plasma glucose (28, 150%) and glucose Ra (20, 60%) throughout the 4-h infusion period in a dose-related manner. The PAF infusions also induced dose-related increases in plasma glucagon and catecholamine levels throughout the infusion period. In a separate group of experiments a complete adrenergic blockade, produced by the constant infusion of propranolol and phentolamine, completely prevented PAF-induced increases in glucose kinetics and the hyperglucagonemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential growth hormone responses to glucose and growth hormone releasing hormone in lactating dairy cows

1989 ◽  
Vol 120 (3) ◽  
pp. 319-325 ◽  
Author(s):  
J. L. Sartin ◽  
A. C. Pierce ◽  
R.J. Kemppainen ◽  
F. F. Bartol ◽  
K. A. Cummins ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Dairy Cows ◽  
Plasma Glucose ◽  
Post Partum ◽  
Regulatory System ◽  
Glucose Infusion ◽  
Differential Growth ◽  
Plasma Ffa ◽  
Hormone Responses ◽  
As Effects

Abstract. Dairy cows in early lactation were reported to secrete growth hormone in response to declining glucose concentrations at day 5 but not day 30 post-partum, whereas GH responses to TRH were reported to be enhanced after day 30 post partum. The present study examined GH response following glucose infusion and the effect of GHRH as well as effects of SRIH on GHRH-stimulated GH release. Declining plasma glucose concentrations after glucose infusion stimulated GH release at day 5 post partum but not in nonpregnant, nonlactating cows or in cows at days 30 and 90 post partum. GHRH stimulated GH release on all days tested, but the response was highest at day 30 post partum when compared to other days. Somatostatin infusion inhibited GHRH effects on GH concentrations only at day 30 post partum and in nonpregnant, nonlactating cows. Thus, a differential response of the GH regulatory system could be demonstrated between days 5 and 30 post partum utilizing different stimuli. Evaluation of plasma glucose and free fatty acid concentrations on days 5, 10, 20, and 30 post partum revealed a progressive decrease in FFA but not glucose as lactation progressed. Decreased plasma FFA concentrations were paralleled by a decrease in basal GH, somatomedin-C and epinephrine. Thus, a decline in FFA may be responsible for the disparity between effects of GHRH and glucose on GH release between days 5 and 30 post partum.

Growth hormone, prolactin and cortisol nyctohemeral variations during naloxone-induced opiate receptor blockade in man

1982 ◽  
Vol 100 (3) ◽  
pp. 321-326 ◽  
Author(s):  
G. Delitala ◽  
M. Giusti ◽  
G. Rodriguez ◽  
G. Mazzocchi ◽  
S. Ferrini ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Bolus Injection ◽  
Opiate Receptors ◽  
Opiate Receptor ◽  
Normal Male ◽  
Opiate Antagonist ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Blood Specimens

Abstract. To evaluate the role of endogenous opioid peptides in prolactin (Prl), growth hormone (GH) and cortisol neuroregulation, 50 mg of the opiate antagonist naloxone was infused over 24 h to 6 normal male volunteers. An additional naloxone dose (5 mg) was given iv as a bolus injection at 20.00 h. Blood specimens were collected hourly by means of a portable constant withdrawal pump. Naloxone failed to alter 24 h secretion of GH and Prl. The sleep-related GH and Prl rise was also unaffected by the opiate blocker. Moreover, naloxone failed to alter the circadian rhythm of cortisol and its 24 h concentration. The results do not suggest a major role of opiate receptors in spontaneous GH, Prl and cortisol secretion in man.

Effect of calcitonin on plasma glucose, C-peptide, glucagon and growth hormone responses to arginine in insulin-dependent diabetic subjects

1981 ◽  
Vol 18 (3) ◽  
pp. 235-241 ◽  
Author(s):  
Saverio Sgambato ◽  
Nicola Passariello ◽  
Dario Giugliano ◽  
Roberto Torella ◽  
Felice D'Onofrio
Keyword(s):  
Growth Hormone ◽  
Plasma Glucose ◽  
C Peptide ◽  
Insulin Dependent ◽  
Hormone Responses ◽  
Insulin Dependent Diabetic

Insulin hypoglycaemia in normal and adrenalectomized subjects: comparison of metabolic parameters and endocrine counter regulation

1981 ◽  
Vol 98 (3) ◽  
pp. 413-419 ◽  
Author(s):  
R. M. Altorfer ◽  
W. H. Ziegler ◽  
E. R. Froesch
Keyword(s):  
Blood Pressure ◽  
Growth Hormone ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Plasma Glucose ◽  
Normal Subjects ◽  
Subjective Symptoms ◽  
Clear Cut ◽  
Insulin Tolerance ◽  
Initial Recovery

Abstract. Insulin tolerance tests were carried out in normal subjects and in adrenalectomized (ADX) patients in order to better understand the importance of counter regulatory hormones for the recovery from hypoglycaemia. Compared to normal subjects recovery of plasma glucose and of free fatty acid levels in adrenalectomized patients is retarded. The levels of glucagon are significantly higher in ADX patients during rest than in normal subjects. As expected, epinephrine and norepinephrine levels did not increase in ADX patients and, accordingly, blood pressure did not change. Growth hormone levels were the same in both groups of subjects. Interestingly, there was no clear-cut difference with regard to subjective symptoms of hypoglycaemia. It would appear that epinephrine is important for the rapid initial recovery from hypoglycaemia, whereas other hormones play a more important role later on.

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