[Regulation of glucose utilization in vivo in man].
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Blood Glucose↗
Biomedical subjects
J Girard
Publications and source records attributed to J Girard.
[Cryptorchism].
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Chorionic Gonadotropin↗
Effects of medium-chain triglyceride feeding or glucose infusion on glucose kinetics in the newborn rat.
Hypoglycaemia which develops in starved newborn rats (0.15 +/- 0.01 mg/ml) is reversed by feeding medium-chain triglycerides (0.66 +/- 0.05 mg/ml). Despite similar glycaemia (0.71 +/- 0.07 mg/ml) starved newborns infused with glucose (10.7 mg/min/kg) show a 30% higher glucose turnover rate than medium-chain triglyceride fed animals (14.1 +/- 0.6 versus 10.6 +/- 0.3 mg/min/kg, p less than 0.01). For a comparable [6-3H]glucose turnover rate (10.5 +/- 0.3 mg/min/kg), glucose-infused (5.25 mg/min/kg) newborns have a 30% lower glycaemia (0.50 +/- 0.03 mg/ml, p less than 0.01) than medium-chain triglyceride-fed newborns. Thus, medium chain triglyceride feeding leads to a 30% decreased capacity of the tissues to utilize glucose. For a similar glucose turnover rate, medium-chain triglyceride-fed newborns have a higher blood lactate concentration than glucose-infused newborns (0.26 +/- 0.03 versus 0.15 +/- 0.02 mg/ml). However, in medium-chain triglyceride-fed newborns, the increase of blood lactate is not only due to the Cori cycle, as glucose recycling is less increased than glucose production. Thus medium-chain triglyceride increases the release of gluconeogenic precursors which are not derived from blood glucose. In presence of a glucose infusion (15.25 mg/min/kg) producing hyperglycaemia (1.35 +/- 0.05 mg/ml), endogenous glucose production is suppressed by only 37%. If 3-mercaptopicolinate, an inhibitor or gluconeogenesis, is given concomitantly, hyperglycaemia is prevented (0.72 +/- 0.08 mg/ml) and endogenous glucose production is suppressed. Glucose infusion in the hypoglycaemic newborn rat might thus lead to a precarious glucose homeostasis.
Animals↗
Effect of insulin on glucose metabolism in adipocytes from virgin and late-pregnant rats.
Under basal conditions (zero insulin), paraovarian adipocytes from 19-day-pregnant rats exhibited the same rates of [U-14C]glucose conversion into CO2 and total lipids as did those from age-matched virgin rats. The dose-response curves for insulin stimulation of glucose metabolism were similar in both groups: maximal response (+100% over basal values) and high sensitivity (half-maximal effect at 0.05 nM-insulin). The present results suggest that the insulin resistance in vivo that occurs during late pregnancy may involve circulating factors lost in vitro.
Adipose Tissue↗
Nerve growth factor induces plasma extravasation in rat skin.
The intradermal application of both mouse and bovine nerve growth factor induced dose-dependently increased vascular permeability as indicated by Evans blue extravasation. Plasma extravasation by nerve growth factor was markedly reduced by capsaicin pretreatment or a combination of H1- and H2-histamine antagonists. The finding that biologically inactive nerve growth factor failed to elicit protein leakage indicates that plasma extravasation by nerve growth factor is a characteristic of the biologically active molecule.
Animals↗
[Pre- and postoperative thyroglobulin secretion into the blood in nodular goiter].
Serum thyroglobulin was measured in patients with a euthyroid, preclinically hyperthyroid or toxic uni- or multinodular goiter (n = 72) prior to and/or 3-12 months following selective resection of the nodular goiter tissue. A sharp decrease in the mean and individually elevated serum thyroglobulin values was observed postoperatively, with normal or undetectable values in 92% of the patients. The pre- and postoperative thyroglobulin levels in multinodular goiter patients with hyperthyroidism, preclinical hyperthyroidism and euthyroidism were 102 +/- 79 micrograms/l vs. 10 +/- 7 micrograms/l; 77 +/- 62 micrograms/l vs. 16 +/- 22 micrograms/l; and 76 +/- 82 micrograms/1 vs. 18 +/- 26 micrograms/1 respectively. The pre- and postoperative values in uninodular goiter patients with TRH-TSH unresponsiveness and with a normal TSH response were 84 +/- 60 micrograms/l vs. 10 +/- 8 micrograms/l, and 105 +/- 115 micrograms/1 vs. less than 6 micrograms/1 respectively. Thus, the elevation of serum thyroglobulin proved to be unrelated to TRH-TSH responsiveness and to thyroid hormone secretion, but to be related to the presence of nodular goiter tissue. Follicular nodules lack normal TSH dependence with respect to goiter maintenance and growth. The results suggest that serum thyroglobulin may represent a marker of autonomous thyroid growth.
Goiter, Nodular↗
[Free thyroxin as a determinant for thyroid function. Evaluation of direct determination of fT4 compared to the oral TRH test].
The diagnostic value of a direct assay of free thyroxine has been evaluated by comparing the concentration of free T4 with the results of an oral TRH test. 147 patients were referred to an endocrine outpatient department because of suspected thyroid dysfunction. Based on clinical investigation and on the results of an oral TRH test, 75 patients were euthyroid, 12 hyperthyroid and 12 hypothyroid. Preclinical hypothyroidism (3 h- TSH value above 35 mE/l and euthyroid peripheral thyroid hormone levels) was found in 25 patients. In 23, preclinical hyperthyroidism (3 h- TSH value after TRH below the sensitivity of the assay, i.e. less than 1 mE/l) together with euthyroid peripheral thyroid hormone values was found. Free thyroxine was assayed using the solid phase technique (Clinical Assay); intraassay coefficients of variation varied between 4.5 and 7.6% and interassay coefficients of variation between 8 and 13%. A normal range for free thyroxine was found between 8.4 and 26.4 pmol/l, the log mean being 14.9 pmol/l. In 12 hyperthyroid patients the free T4 concentration was above 49.4 pmol/l, while the mean of 12 hypothyroid patients was below 4.4 pmol/l. The mean free T4 concentrations in the syndromes of preclinical hypo- and hyperthyroidism, which by definition are only recognizable by the TSH increase in response to TRH, were within the normal range. Using the sensitive TRH test as a comparison, the present investigation thus confirms the reliability of direct assay of free T4 for the diagnosis of thyroid function in clinical practise.(ABSTRACT TRUNCATED AT 250 WORDS)
Female↗
Quantitative analysis of ACTH-immunoreactive cells in the anterior pituitary of young spontaneously hypertensive and normotensive rats.
ACTH-immunoreactive cells in the anterior pituitary of 4-week-old spontaneously hypertensive rats (SHR) were studied with immunocytochemical and morphometric techniques. The results were compared with data from age-matched normotensive Wistar-Kyoto rats (WKY). No significant differences were found in volume density and average size of ACTH-immunoreactive cells between these two strains. However, SHR showed a significantly larger anterior lobe (2 P less than 0.01) than WKY, indicating that the total number of ACTH-immunoreactive cells in the anterior pituitary is greater in SHR than in WKY. These data are in agreement with radioimmunological determinations showing a significantly elevated content (2P less than 0.01) but only a moderately higher concentration (0.05 less than 2P less than 0.10) of ACTH in the anterior pituitary of SHR as compared to WKY. The present results suggest an enhanced availability of ACTH in the anterior pituitary of 4-week-old SHR, a fact which could explain the markedly enhanced stress-induced release of ACTH previously found in these animals. This study further supports the hypothesis that, among other factors, an instability of the hypothalamo-pituitary-adrenal axis may contribute to the development of genetically programmed hypertension.
Adrenocorticotropic Hormone↗
Effect of physiological elevation of plasma growth hormone levels on ketone body kinetics and lipolysis in normal and acutely insulin-deficient man.
The effect of physiological elevation of growth hormone levels on ketone body kinetics was determined using a 14C-ketone body tracer technique in normal and acutely insulin-deficient man. Changes of ketone body production and metabolic clearance rates during growth hormone infusion (plasma levels of approximately 25 micrograms/1) were measured during basal conditions and during heparin-induced elevation of non-esterified fatty acid levels. Growth hormone administration to six subjects fasted overnight resulted in an increase in ketone body production which exceeded that observed in nine control subjects (5.5 +/- 0.5 versus 3.1 +/- 0.1 mumol X kg-1 X min-1, p less than 0.025) after elevation of plasma non-esterified fatty acids. Growth hormone infusion increased glycerol and non-esterified fatty acid concentrations indicating enhanced lipolysis. During somatostatin-induced acute insulin deficiency (n = 7), growth hormone enhanced the increase in total ketone body production observed in six subjects receiving somatostatin alone (8.4 +/- 0.8 versus 4.1 +/- 0.7 mumol X kg-1 X min-1, p less than 0.01). Total ketone body metabolic clearance decreased by 50% during somatostatin and remained uninfluenced by growth hormone. Non-esterified fatty acids and glycerol levels increased during somatostatin, and growth hormone failed to alter non-esterified fatty acid levels significantly. The results demonstrate a stimulatory effect of high physiological growth hormone levels on ketogenesis which is largely explained by an enhancement of lipolysis and thus increase in substrate supply for ketogenesis. Growth hormone administration during acute insulin deficiency enhanced ketogenesis in the absence of alterations in plasma non-esterified fatty acid levels, suggesting a direct hepatic ketogenic effect.
Aged↗
Glucose turnover and recycling in unrestrained and unanesthetized 48-h-old fasting or post-absorptive newborn pigs.
The metabolism of glucose has been studied in 48-h-old unanesthetized fasting and post-absorptive sucking piglets. Both [6-3H]- and [U-14C]glucose were administered either by a single injection method or by a primed infusion technique. The rates of glucose turnover and recycling were estimated under steady-state conditions. The rates of glucose turnover and recycling in 48-h-old fasting or post-absorptive piglets were not statistically different when measured using the single injection technique or the primed infusion method. The mean (with SE) rate of glucose turnover was 65.8 (2.5) in post-absorptive and 31.1 (1.9) mumol/kg per min in fasted newborn pigs. Glucose utilization was linearly related to blood glucose concentration; regression analysis indicated a y-intercept of 7.2 mumol/kg per min. As tested by arterio-portal differences the gut was not releasing glucose or galactose in 5 h-post-absorptive sucking newborn pigs. Thus, the higher rates of glucose turnover in post-absorptive newborn pigs compared with fasting ones suggest that hepatic glucose production is enhanced in post-absorptive sucking piglets. The mean (with SE) rates of glucose recycling were four times higher in post-absorptive piglets than in fasting ones, i.e. 14.4 (1.6) and 3.7 (0.5)% of [6-3H]glucose turnover respectively. As liver glycogen was exhausted in 48-h-old sucking piglets, this suggests that hepatic glucose production results from gluconeogenesis.
Animals↗
Pregnancy-induced insulin resistance in the rat: assessment by glucose clamp technique.
To quantify and characterize the insulin resistance during pregnancy in the rat, a euglycemic hyperinsulinemic clamp was set up. Dose-response curves for the effects of five concentrations of insulin on glucose production, glucose utilization, and glucose clearance were performed in age-matched virgin and 19-day-pregnant rats. Glucose production and glucose utilization were measured by using [3-3H]-glucose. Glucose production was totally suppressed at plasma insulin concentrations higher than 1,000 microU/ml in the two groups. Insulin concentration causing half-maximal suppression of glucose production was about 70 microU/ml in virgin rats and 250 microU/ml in pregnant rats. Maximal glucose utilization was obtained at plasma insulin concentrations of 2,000 microU/ml. In pregnant rats maximal increment in glucose utilization was significantly lower (P less than 0.01) than in virgin rats. Insulin concentrations causing half-maximal stimulation of glucose utilization were 200 microU/ml in virgin rats and 500 in pregnant rats. As blood glucose concentration in virgin and pregnant rats was clamped at, respectively, 0.97 +/- 0.03 and 0.73 +/- 0.03 mg/ml, glucose clearance rates were calculated because this parameter is minimally affected by the changes in blood glucose concentrations. A normal maximal increment in glucose clearance in response to insulin was restored in pregnant rats but the rightward shift of the dose-response curve was maintained. Plasma insulin concentrations necessary for half-maximal increment of glucose clearance in the two groups were similar to that observed when the results were expressed as glucose utilization. Thus, insulin resistance during late pregnancy in the rat is characterized by a decreased sensitivity of liver and peripheral tissues to insulin.
Animals↗
Plasma secretin and pancreatic response to various stimulants including a meal.
In dogs with gastric and duodenal Thomas cannulas, we investigated the threshold dose range of exogenous secretin and intraduodenal HCl for pancreatic bicarbonate secretion and, with a recently developed radioimmunoassay, measured the increase in plasma secretin concentrations. Synthetic secretin (2.5, 7.5, and 22.5 ng X kg-1 X h-1) was dissolved in saline or 0.1% dog albumin and given with or without a background infusion of 30 ng X kg-1 X h-1 of caerulein. The minimal dose of secretin that elicited a significant pancreatic bicarbonate response as well as an increase in plasma secretin concentration was 7.5 ng X kg-1 X h-1 when administered with albumin and 22.5 ng X kg-1 X h-1 without albumin. The threshold dose for duodenal HCl was 2 mmol X h-1. The threshold secretin dose for bicarbonate secretion and for an increase in plasma secretin levels was unchanged with a background caerulein infusion. Furthermore, postprandial secretin concentrations were measured. After a meat meal plasma secretin release appeared to occur in spikes up to 10 pmol X l-1 corresponding to secretin levels seen during infusion of 7.5 ng X kg-1 X h-1 of secretin and intraduodenal acid perfusion at a dose of 2 mmol X h-1.
Animals↗
Importance of the adrenal cortex for development and maintenance of hypertension in spontaneously hypertensive rats.
Adrenal regeneration following complete bilateral adrenalectomy in spontaneously hypertensive rats (SHR) was used to study the significance of glucocorticoid and mineralocorticoid hormones for the development and maintenance of hypertension. Pre-hypertensive (5 weeks of age) and hypertensive (10 and 16 weeks of age) male SHR underwent adrenalectomy (ADN) and were kept on 0.9% NaCl. The rats were ether stressed at various intervals to assess adrenal steroid production. Following ADN of all three age groups the development or maintenance of hypertension depended on the presence of adrenal regenerates. Animals without signs of adrenal regeneration remained or became normotensive. There was a significant correlation between plasma corticosterone levels following ether stress and blood pressure. Aldosterone and corticosterone production of regenerates and of adrenal cortex of intact SHR was studied in vitro. Under basal condition and following ACTH stimulation both tissues produced similar amounts of corticosterone, however considerably less aldosterone was secreted by regenerates. Betamethasone substitution in adrenalectomized rats caused a dramatic increase of blood pressure which was attenuated by L-propranolol. Aldosterone had no significant effect on blood pressure. It is concluded that glucocorticoids play a permissive role in the development of hypertension presumably via alteration of sympathetic neurotransmission.
Adrenal Cortex↗
[4 years' experience with combined hormonal treatment of cryptorchism].
86 patients aged 9 months to 15 years (means = 4.8) having 102 cryptorchid testes were treated with either LHRH nasal spray or with a combination of LHRH and HCG. The immediate success rate after the termination of treatment was 74%. The follow-up showed that 65% of the testes were still descended after the critical period had elapsed. An open processus vaginalis was found in 74% (20/27) while pathological changes of the epididymis (64%) (7/11) and testis "reflexus" (48%) (13/27) were frequently encountered in unsuccessfully treated patients. Furthermore, the above grouping of patients displayed typical histological changes associated with cryptorchidism, namely an impaired number of germ cells (0.14 S/T median values) and atrophy of the Leydig cells. In almost all of the patients classified as treated unsuccessfully, there was a definite improvement in the position of the gonad, thus facilitating subsequent surgery.
Adolescent↗
[Development and regulation of ketogenesis in isolated hepatocytes in the newborn rabbit].
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Animals↗
[Technics for studying insulin resistance in vivo].
Insulin resistance is found in physiological (starvation, gestation) or pathological (diabetes, obesity, uremia, cortisol or growth hormone excess) situations. In order to study insulin resistance, a number of tests have been developed which have evolved in term of practical and conceptual complexity. In the present paper, these tests are analyzed for their reliability in answering the following questions: does an insulin resistance exist? Is it possible quantify it? What are the causes (receptor or post receptor defect) and the tissues producing or utilizing glucose involved in insulin resistance? Emphasis is placed upon a newly developed technique: the euglycemic, hyperinsulinemic glucose clamp. Progress in the knowledge of insulin resistance as well as the problems or limitations linked to this latter technique are discussed.
Blood Glucose↗
Septo-optic pituitary dysplasia. Observations on three patients.
Septo-optic pituitary dysplasia is a relatively rare but pathophysiologically interesting malformation of the brain midline structures including optic chiasm and nerves, hypothalamus, neurohypophysis and septum pellucidum. The lesion develops between the 5th and 8th week of pregnancy. The cause is unknown but heredity seems unlikely. Symptoms result from hypothalamic and neurohypophyseal insufficiency of variable severity combined with reduced vision due to hypoplasia of optic nerves and chiasm. Prognosis is variable, depending on the severity of the defect as well as on the earliest time of diagnosis followed by suitable hormone substitution and specialized care of blindness. We present the clinical course in three patients and the pathological findings in one patient who died in the 14th month of life.
Child↗
Direct assay of free thyroxine in the newborn.
Several reagent sets are available, which allow a direct assay without dialysis of the free, bioavailable part of total thyroxine in plasma. A methodological investigation showed that the solid phase (coated tubes) kit from Clinical Assay gives reproducible results in plasma volumes of 50 microliter. Plasma samples from 95 newborns have been assayed at the 4th to 5th day of life. The mean concentration for free thyroxine of 62 infants born at term was 17 pmol/l with a log 2 SD range of 10-28 pmol/l. This value is similar to the normal value in adults (15.1 pmol/l, log 2 SD range 8.3-27.4 pmol/l). This is in contrast to the total T4 concentration: mean value for newborns 182 nmol/l (normal range 2 SD log 130-250 nmol/l) compared to a mean of 90 nmol/l (normal range 2 SD log 51-157) for adults. Mean free T4 concentration was 11.5 pmol/l in 18 premature infants (gestational ages 34-35 weeks: mean 8.7 pmol/l; gestational ages 36-37 weeks: mean 15.3 pmol/l). The lowest concentrations were found in infants with a respiratory distress syndrome: mean 8.9 pmol/l. TSH did not exceed 10 mU/l. It is concluded that the method used allows a direct estimation of free T4 in small plasma samples and allows a rapid decision in suspected thyroid disorders in infants.
Humans↗