Effects of insulin on glucose metabolism and glucose transport in fat cells of hormone-treated hypophysectomized rats: evidence that growth hormone restricts glucose transport.

In earlier studies we have shown that insulin does not stimulate glucose incorporation in adipocytes of hypophysectomized (hypox) rats. Basal glucose incorporation is decreased, although basal 3-O-methylglycose transport is very rapid and cannot be further stimulated by insulin. In this study we treated hypox rats with human GH, ACTH, and T3, alone or in combination, and examined the effects of insulin on glucose incorporation into fat cells and on 3-O-methylglucose transport. The results show that chronic administration of T3 alone to hypox rats partially restores glucose incorporation into fat cells and, in combination with ACTH, completely restores this incorporation. The two hormones have no effect on the glucose carrier system. The transport rate under T3 and ACTH replacement therapy continues to proceed at a maximal rate, so that basal glucose incorporation is high but not further enhanced by insulin. In contrast, administration of human GH to hypox rats does not influence glucose incorporation but has a marked effect on glucose transport. The basal glucose transport rate returns toward normal and again responds to insulin. This suggests 1) that enzyme activities responsible for the lipogenetic capacity of the fat cell are decreased in hypox rats and returned toward normal by the combined T3/ACTH treatment, and 2) that the limitation of glucose transport in the fat cell is controlled by GH. GH seems to induce a change of the glucose-carrier system; it leads to a restriction of glucose transport, which is acutely modulated by insulin.     

The effects of recombinant human growth hormone on body composition and glucose metabolism in HIV-infected patients with fat accumulation

GH has been proposed as a therapy for patients with HIV-associated fat accumulation, but the pharmacological doses (6 mg/d) used have been associated with impaired fasting glucose and hyperglycemia. In contrast, physiologic doses of GH ( approximately 1 mg/d) in HIV-negative men reduced visceral adiposity and eventually improved insulin sensitivity, despite initially causing insulin resistance. We conducted an open-label study to evaluate the effects of a lower pharmacologic dose of GH (3 mg/d) in eight men with HIV-associated fat accumulation. Oral glucose tolerance, insulin sensitivity, and body composition were measured at baseline, and 1 and 6 months. Six patients completed 1 month and 5, 6 months of GH therapy. IGF-I levels increased 4-fold within 1 month of GH treatment. Over 6 months, GH reduced buffalo hump size and excess visceral adipose tissue. Total body fat decreased (17.9 +/- 10.9 to 13.5 +/- 8.4 kg, P = 0.05), primarily in the trunk region. Lean body mass increased (62.9 +/- 6.4 to 68.3 +/- 9.1 kg, P = 0.03). Insulin-mediated glucose disposal, measured by a euglycemic hyperinsulinemic clamp, declined at month 1 (49.7 +/- 27.5 to 25.6 +/- 6.6 nmol/kg(LBM).min/pmol(INSULIN)/liter, P = 0.04); values improved at month 6 (49.2 +/- 22.6, P = 0.03, compared with month 1) and did not differ significantly from baseline. Similarly, the integrated response to an oral glucose load worsened at month 1 (glucose area under the curve 20.1 +/- 2.3 to 24.6 +/- 3.7 mmol.h/liter, P < 0.01), whereas values improved at month 6 (22.1 +/- 1.5, P = 0.02, compared with month 1) and did not differ significantly from baseline. One patient developed symptomatic hyperglycemia within 2 wk of GH initiation; baseline oral glucose tolerance testing revealed preexisting diabetes despite normal fasting glucose. In conclusion, GH at 3 mg/d resulted in a decrease in total body fat and an increase in lean body mass in this open-label trial. While insulin sensitivity and glucose tolerance initially worsened, they subsequently improved toward baseline. However, the dose of GH used in this trial was supraphysiologic and led to an increase in IGF-I levels up to three times the upper normal range. Because there are known adverse effects of long-term GH excess, the effectiveness of lower doses of GH should be studied. We also recommend a screening oral glucose tolerance test be performed to exclude subjects at risk for GH-induced hyperglycemia.     

Effects of recombinant human growth hormone on hepatic lipid and carbohydrate metabolism in HIV-infected patients with fat accumulation

We recently reported that treatment with a pharmacologic dose of recombinant human growth hormone (GH) resulted in a significant loss of body fat and gain in lean tissue in HIV-infected patients with syndromes of fat accumulation. However, insulin-mediated glucose disposal decreased transiently after one month of GH therapy. The present paper focuses on the changes of hepatic carbohydrate and fat metabolism associated with GH treatment in the same subjects. We assessed hepatic insulin sensitivity under both fasting and hyperinsulinemic-euglycemic clamp conditions prior to and after one and six months of GH treatment (3 mg/day) in five patients using stable isotope tracer techniques. Indirect calorimetry, and measurements of lipid concentrations. Fasting endogenous glucose production (EGP) increased significantly at one month (12.0 +/- 0.7 to 14.9 +/- 0.9 micromol/kg/min, P < 0.03), and the increase was sustained at six months of GH treatment (14.0 +/- 1.1 micromol/kg/min, NS). This increase in EGP was driven in part by increased glucogenesis (GNG) (3.5 +/- 0.9 to 5.2 +/- 0.9 and 5.8 +/-1.2 micromol/kg/min, n = 4, P < 0.01 and P < 0.01 at one and six months, respectively); small changes in hepatic glycogenolysis also contributed. Sustained increases in lipolysis and progressive decreases in hepatic fractional de novo lipogenesis (DNL) and triglyceride concentrations occurred with GH treatment. These changes were accompanied by an improved lipid profile with a significant increase in HDL cholesterol and significant decreases in total and LDL cholesterol and triglyceride levels, the latter consistent with the decrease in hepatic DNL. During a hyperinsulinemic-euglycemic glucose clamp, EGP and GNG were markedly suppressed compared to the corresponding time points under fasting conditions, albeit less so when measured after one month of GH treatment. Thus, in HIV-infected patients with abnormal fat distribution, pharmacologic doses of GH improved the overall lipid profile, but worsened glucose homeostasis under both fasting and hyperinsulinemic conditions. The combined implications of these positive and negative metabolic effects for cardiovascular disease risk remain unknown.     

Effects of human growth hormone on insulin-stimulated glucose metabolism in 3T3-F442A adipocytes

GH is believed to play a role in promoting insulin resistance in patients with diabetes and with GH excess. The means by which GH produces insulin resistance may be through direct suppression of glucose metabolism in target cells (insulin-independent) or by interfering with the ability of insulin to stimulate glucose metabolism (insulin-dependent). In 3T3-F442A adipocytes, long term incubation (24-72 h) with GH directly inhibits glucose oxidation and lipid synthesis in the absence of insulin. To distinguish the insulin-independent effects of GH on glucose metabolism from the insulin-dependent effects of GH, we examined the effect of GH on insulin-stimulated lipid accumulation in cultured 3T3-F442A adipocytes. Cells were incubated for 48-72 h with GH and then treated with insulin. Insulin stimulated lipid accumulation in GH-pretreated and control cells. Compared to control, GH-treated cells had lower absolute levels of lipid accumulation in the absence of insulin and at each insulin concentration tested. Thus, GH directly suppresses basal lipid accumulation and lowers the response to insulin. In addition, a 10 times higher insulin concentration was required to reach maximum stimulation of lipid accumulation in GH-treated cells (50 ng/ml) than in control cells (5 ng/ml). When cells were exposed simultaneously to insulin and GH for 72 h, GH treatment inhibited the ability of insulin to stimulate lipid accumulation, and the degree of suppression by GH was related to the GH concentration present. These observations suggest that GH suppresses glucose metabolism not only in the absence but also in the presence of insulin. Since short term (4-h) incubation with GH increases glucose metabolism transiently in GH-deficient preparations, we also examined the influence of short term incubation with GH on insulin responses. Cells were incubated for 4 h with varying concentrations of insulin in the simultaneous presence or absence of GH. Insulin stimulated the conversion of glucose to lipid when tested alone or in the presence of GH. Short term exposure to GH alone also stimulated glucose metabolism. The stimulation of lipid accumulation at insulin concentrations less than 5 ng/ml was greater with GH, but responses were comparable above 5 ng/ml insulin. The ability of insulin to bind to its receptor was not affected by prior treatment with GH for either short or prolonged time periods.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect of polyethylene glycol recombinant human growth hormone on growth and glucose metabolism in hypophysectomized rats

ObjectiveTo study the effect of polyethylene glycol recombinant human growth hormone on growth and glucose metabolism in hypophysectomized rats, and compare the effect of treatment between recombinant human growth hormone (rhGH) and polyethylene glycol rhGH (PEG-rhGH).MethodsHypophysectomy was performed in juvenile rats to build the animal model of GH deficiency. The hypophysectomized animals were randomly assigned into three groups and treated with saline (negative control, n = 20), rhGH (n = 20) and PEG-rhGH (n = 20). A sham operation was performed to set up the normal control (n = 20). Body weight, body length and tail length were recorded every 2 days for a 14-day treatment and bone growth was measured at the end of therapy. Glucose infusion rate (GIR) determined by euglycemic hyperinsulinemic clamp was used to evaluate insulin sensitivity after GH treatment. We also examined plasma glucose and serum insulin levelsResultsCompared with the negative control, the body weight, body length, tail length and bone growth increased significantly in hypophesectomized rats treated by GH (P < 0.01). Although the weight gain in the first 10 days was higher in the PEG-rhGH group than in the rhGH group (P < 0.05), the growth promoting effect was similar between rhGH and PEG-rhGH (P > 0.05). Neither rhGH nor PEG-rhGH impaired glucose tolerance of rats after hypophesectomy. Compared with negative controls, according to decreased serum insulin, reduced insulin expression in pancreatic cells and increased GIR in the clamp, both rhGH and PEG-rhGH groups had improved insulin sensitivity within 14 days (P < 0.01). However, with prolonged treatment, the GIR in the rhGH-treated rats decreased significantly (P < 0.05); while PEG-rhGH did not interfere with GIR, even after a doubled dose (P > 0.05).ConclusionsPEG-rhGH had the same linear growth promoting efficacy as unmodified rhGH. The short-term GH replacement could improve insulin sensitivity in hypophysectomized rats, especially after PEGylation.     

Effects of pituitary hormone deficiency on growth and glucose metabolism of the sheep fetus

Pituitary hormones are essential for normal growth and metabolic responsiveness after birth, but their role before birth remains unclear. This study examined the effects of hypophysectomizing fetal sheep on their growth and glucose metabolism during the late normal and extended periods of gestation, and on their metabolic response to maternal fasting for 48 h near term. Fetal hypophysectomy reduced crown rump length (CRL), limb lengths, and body weight but increased ponderal index relative to controls near normal term. It also lowered the daily rate of crown rump length increment uniformly from 35 d before, to 20 d after normal term. Hypophysectomized (HX) fetuses had normal weight-specific rates of umbilical uptake, utilization, and oxidation of glucose but lower rates of umbilical oxygen uptake than controls near term. All these metabolic rates were significantly less in HX fetuses during the extended period of gestation than in HX and intact fetuses near normal term. In contrast to controls, glucogenesis was negligible in HX fetuses during maternal fasting. Consequently, the rate of glucose utilization decreased significantly in fasted HX but not intact fetuses. Conversely, the rate of CO(2) production from glucose carbon decreased in fasted intact but not HX fetuses. Fetal hypophysectomy also prevented the fasting-induced increases in plasma cortisol and norepinephrine concentrations seen in controls. These findings demonstrate that the pituitary hormones are important in regulating the growth rate and adaptive responses of glucose metabolism to undernutrition in fetal sheep. They also suggest that fetal metabolism is altered when gestational length is extended.     

Influence of norepinephrine,growth hormone and fasting on FFA mobilization and glucose metabolism in lean and obese subjects

Summary The influence of norepinephrine (NE), human growth hormone (HGH) and fasting on FFA mobilization and carbohydrate metabolism has been studied in 47 obese females and 72 nonobese control subjects (35 females and 37 males). — Weight-related doses of NE infused for 2 h (0.1 /kg/min) induced a much greater rise in plasma FFA and blood glucose concentrations in obese than in normal subjects. With a fixed dose (10 /min for 2 h), FFA response was still significantly higher in the overweight than in the lean subjects, while glucose réponses were similar in both groups. Among the control subjects, males and females behaved similarily. — The plasma FFA rise observed in the 4 h following thei. v. injection of HGH (10 mg) was not statistically different in obese females, normal males and normal females. — These results suggest that human obese adipose tissue has no impaired sensitivity toward the lipolytic action of NE and HGH. — During fasting, obese, when compared with normal subjects, showed a smaller increase in plasma FFA level together with a smaller decrease in glucose flux. The possible relationship between these 2 anomalies is discussed, considering that glucose deficiency has a major role in regulating FFA mobilization during fasting.

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Einflu von Noradrenalin, Wachstumshormon und Fasten auf die FFS-Freisetzung und den Glucosestoffwechsel bei Übergewichtigen und Normalpersonen

Zusammenfassung Die Wirkung von Noradrenalin, Wachstumshormon und Fasten auf die Mobilisierung der freien Fettsäuren und den Glucosestoffweehsel wurde bei 47 übergewichtigen Frauen und 72 Kontrollpersonen (35 Frauen und 37 Männern) verglichen. — Nach einer zweistündigen Infusion mit 0,1 g/kg/min führte das Noradrenalin zu einem Anstieg der Plasma-FFS und des Blutzuckerspiegels, der bei den Übergewichtigen wesentlich stärker ausgeprägt war als bei den Normalpersonen. Mit einer konstanten Dosis von 10 g/min fiel die Steigerung der FFS bei den Adipösen immer noch signifikant höher aus, während der blutzuckersteigernde Effekt in beiden Kollektiven die gleiche Größenordnung erreichte. Die Kontrollpersonen zeigten keinen signifikanten Unterschied im Verhalten der beiden Geschlechter. — Die Erhöhung der FFS nach i.v. Verabreichung von menschlichem Wachstumshormon (10 mg) wurde über 4 Std. verfolgt, wobei sich keine Unterschiede zwischen den übergewichtigen Frauen und den Normalpersonen beider Geschlechter ergaben. — Diese Ergebnisse lassen vermuten, daß das Fettgewebe bei Adipösen eine normale Empfindlichkeit gegenüber der Wirkung von Noradrenalin und Somatotropin aufweist. — Fasten führte bei den übergewichtigen Patienten zu einem geringeren Anstieg der FFS und zu einer weniger ausgeprägten Reduktion des Glucoseabstroms als bei den Kontrollpersonen. Die möglichen Beziehungen zwischen den beiden Anomalien werden unter Berücksichtigung der Rolle diskutiert, die die der Glucosemangel bei der Fettmobilisierung während des Fastens spielt.

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Influence de la noradrénaline, de l'hormone de croissance et du jeûne sur la mobilisation des FFA et sur le métabolisme glucidique chez des sujets obèses et normaux

Résumé L'action de la noradrénaline, de l'hormone de croissance et du jeûne sur la mobilisation des FFA et sur le métabolisme glucidique a été comparée chez 47 femmes obèses et 72 sujets témoins (35 femmes et 37 hommes). — Perfusée pendant 2 h à une dose proportionnelle au poids (0.1 /kg/min), la noradrénaline provoque un accroissement des FFA plasmatiques et de la glycémie qui est beaucoup plus important chez les obèses que chez les normaux. Avec une dose fixe de 10 /min pendant 2 h, l'élévation des FFA est encore significativement plus élevée chez les sujets obèses alors que l'effet hyperglycémiant est de même amplitude dans les 2 groupes. Parmi les sujets témoins, il n'y a pas de différence significative entre les réponses des 2 sexes. — L'élévation des FFA mesurée pendant les 4 h suivant l'injection i.v. d'hormone de croissance humaine (10 mg) est comparable chez les femmes obèses et les sujets témoins des 2 sexes. — Ces données suggèrent que le tissu adipeux des obèses présente une sensibilité normale à l'action de la noradrénaline et de l'hormone de croissance. — Lorsqu'ils sont soumis au jeûne, les patients obèses présentent un accroissement moindre des FFA et une réduction moins marquée du flux glucosé que les sujets normaux. Les relations possibles entre ces deux anomalies sont discutées en tenant compte du rôle majeur que joue la carence en glucose dans la mobilisation lipidique au cours du jeûne.

     

Effects of thyrotropin-releasing hormone on sleep and sleep-related growth hormone release in normal subjects.

Effects of TRH on sleep and sleep-related growth hormone (GH) release were examined in four normal volunteers. A bolus of 500 microgram of synthetic TRH was injected iv at the onset of sleep, followed by continuous iv infusion of 1000 microgram of TRH dissolved in saline for 3 h on two nights. Saline alone was infused on two control nights in each of these subjects. Polygraphic sleep records showed that TRH transiently interrupted sleep on both nights in all of the four subjects. The arousal phenomenon was observed from 80 to 151 min after the start of TRH administration until 20 to 212 min after the end of TRH infusion. The mean (+/-SE) percentage of awakening on the nights of TRH administration was significantly larger than on the control nights (36.4 +/- 1.9% vs. 1.3 +/- 0.8%, P less than 0.001). Plasma GH increased in close relationship to the initial appearance of slow wave sleep (SWS) within 40 min after sleep onset on both control nights in all four subjects. On nights of TRH administration, however, plasma GH levels during the initial 80 min of sleep were significantly lower (P less than 0.005) than on control nights, whereas SWS was demonstrated before the interruption of sleep. On nights when sleep was interrupted by forced wakefulness 1 h after sleep onset, plasma GH rose to levels comparable to those on control nights during early sleep periods in all subjects examined. These results suggest that TRH inhibits sleep and sleep-related GH release in normal subjects.     

Glucose and fat metabolism in adults with growth hormone deficiency

OBJECTIVE Adults with long-standing GH deficiency have a decreased lean body mass and an increased fat mass. We investigated the effects of the abnormal body composition on glucose turnover and fuel metabolism. DESIGN Cross-sectional analysis. PATIENTS Twenty-four adults with acquired GH deficiency and a wide range of adiposity (body mass index from 18·8 to 42·3 kg/m²). MEASUREMENTS In the post-absorptive state glucose turnover was measured following intravenous injection of 3-³H-glucose and leucine oxidation was assessed following intravenous injection of 1-¹⁴C-leuclne. Glucose and fat oxidation were calculated from indirect calorimetry using protein oxidation derived from leucine oxidation. RESULTS Total glucose turnover was 692 ± 146 μmol/min (mean ± SD) and Increased with height (r= 0·70, P= 0·0003) and with lean body mass (LBM) (r= 0·80, P < 0·0001). Glucose turnover expressed per kg LBM was in the published normal range (14·2 ± 2·1 pmol/kg LBM min). Glucose oxidation was 47 ± 27% of glucose turnover and increased with LBM (r= 0·59, P= 0·008) but not with height (r= 0·32, NS). Glucose turnover increased with increasing fat oxidation (r= 0·61, P= 0·006). The non-oxidative part of glucose turnover was positively correlated with fat oxidation (r= 0·82, P= 0·0001) and inversely with the respiratory quotient (r= -0·81, P < 0·0001). Ketone body concentration (r= 0·55, P= 0·03), but not free fatty acid levels (r= 0·21, NS), correlated with fat oxidation. Fasting plasma glucagon levels were elevated (35 ± 13 vs 9 ± 19pmol/l (published controls) and inversely related to lean body mass (r= -0·44, P= 0·04). CONCLUSIONS Adults with GH deficiency studied after an overnight fast have changes In glucose and fuel metabolism seen In normal subjects after more prolonged fasting suggesting that adults with hormone deficiency have reduced carbohydrate stores.     

Comparative potency of subtilisin-cleaved and intact human growth hormone measured in growth hormone-deficient human subjects.

Eight GH-deficient subjects received both subtilisin-cleaved human GH (hGH-S) and intact hGH (hGH-I) during short term balance studies to compare the potency of these two forms of GH. Both forms caused nitrogen retention, calciuria, postassium retention, and elevation of blood glucose. The effects on plasma insulin concentrations were inconstant at the doses used. hGH-S was more potent than hGH-I, as measured by nitrogen and potassium retention, and the differences reached levels of statistical significance. hGH-S also caused greater calciuria and increases in fasting the postprandial blood glucose and in postprandial insulin in absolute terms, but these differences did not reach levels of statistical significance. In no instance was hGH-I significantly more potent than hGH-S. We conclude hGH-S, a two-chain form of hGH, caused significantly greater nitrogen and potassium retention in human subjects in short term balance studies than hGH-I.     

Effects of a physiological growth hormone pulse on substrate metabolism in insulin-dependent (type 1) diabetic subjects.

When present in inappropriate amounts GH induces substantial insulin resistance and it has furthermore been suggested that modest nocturnal surges of GH may precipitate the emergence of the dawn phenomenon. To characterize the metabolic effects of physiologically relevant, small-scale GH exposure, six type 1 diabetic subjects were studied for 5 h in the postabsorptive state after an iv pulse of either 210 micrograms GH or saline. Identical amounts of insulin were infused on both occasions to maintain a prevailing blood glucose concentration of 125 +/- 12 mg/100 ml. The GH bolus caused an increase in serum GH levels to a peak value of 22 +/- 2 micrograms/L after 10 min, a 70% increase in serum FFA (from 570 +/- 80 to 980 +/- 60 mumol/L) and a 400% increase in blood 3-hydroxybutyrate (3-OHB) (from 100 +/- 15 to 420 +/- 35 mumol/l) concentrations after 180 and 240 min respectively (P less than 0.05). Blood glycerol and forearm uptake of 3-OHB rose in parallel (P less than 0.01). Plasma glucose, isotopically measured glucose turnover and forearm glucose uptake was not affected by GH. Blood lactate concentrations increased (P less than 0.05) and nonoxidative glucose use and lipid oxidation tended to increase with GH. Energy expenditure remained unaffected. These results suggest that under everyday conditions GH acts as an important regulator of fuel fluxes in type 1 diabetic subjects, the main effect being a transient stimulation of lipolysis. Since no significant effect on glucose metabolism was recorded, we do not presently find evidence to support a primary role for small surges of GH in the pathogenesis of the dawn phenomenon.     

Effects of growth hormone on lipid metabolism in humans

The most immediate effect of growth hormone (GH) administration in humans is a significant increase in free fatty acids after 1–2 h, reflecting stimulation of lipolysis and ketogenesis. This stimulation represents an important physiological adaptation to stress and fasting. When the capacity of GH to increase lipolysis is blocked, the protein-retaining and insulin-antagonistic effects of GH on glucose metabolism are either abolished or weakened dramatically, compatible with a key role for lipolysis in orchestrating the metabolic actions of GH.     

Reduced glucose incorporation to triglycerides following chronic exposure of human fat cells to growth hormone

Using the tissue culture technique we have recently demonstrated that long-term exposure of human adipose tissue to human growth hormone (GH) in vitro leads to an impairment in glucose incorporation into triglycerides. This effect was further studied in the present investigation. Biopsies of human adipose tissue which had been cultured for one week with or without GH were studied in subsequent short-term incubations where the conversion of glucose to CO2 and to total lipids was determined. The formation of CO2 was not changed by previous exposure of the biopsies to GH whereas the incorporation of glucose into triglycerides was reduced by about one third. Total glucose metabolism, as determined from the sum of the two pathways, was significantly reduced. The activities of three glycolytic enzymes were determined in biopsies of human adipose tissue which had been cultured with or without GH for one week. The activity of phosphofructokinase was reduced, while the hexokinase and the glucose-6-phosphate dehydrogenase activities were unchanged. The diminished activity of phosphofructokinase, the enzyme considered to be rate-limiting for glycolysis in human fat cells, may be responsible for the decreased rate of glucose metabolism found.     

Effects of high-dose growth hormone on glucose and glycerol metabolism at rest and during exercise in endurance-trained athletes

CONTEXT: Recombinant human-GH (r-hGH), in supraphysiological doses, is self-administered by athletes in the belief that it is performance enhancing. OBJECTIVE: The objective of this study was to determine whether r-hGH alters whole-body glucose and glycerol metabolism in endurance-trained athletes at rest and during and after exercise. DESIGN: This was a 4-wk double-blind placebo-controlled trial. SETTING: This study was conducted at St. Thomas Hospital (London, UK). PARTICIPANTS: Twelve endurance-trained male athletes were recruited and randomized to r-hGH (0.2 U/kg.d) (n = 6) or identical placebo (n = 6) for 4 wk. One (placebo group) withdrew after randomization. INTERVENTION: Intervention was conducted by randomization to r-hGH (0.2 U/kg x d) or identical placebo for 4 wk. MAIN OUTCOME MEASURES: Whole-body rates of appearance (Ra) of glucose and glycerol (an index of lipolysis) and rate of disappearance of glucose were measured using infusions of d-[6-6-2H2]glucose and 2H5-glycerol. RESULTS: Plasma levels of glycerol and free fatty acids and glycerol Ra at rest and during and after exercise increased during r-hGH treatment (P < 0.05 vs. placebo). Glucose Ra and glucose rate of disappearance were greater after exercise during r-hGH treatment (P < 0.05 vs. placebo). Resting energy expenditure and fat oxidation were greater under resting conditions during r-hGH treatment (P < 0.05 vs. placebo). CONCLUSIONS: r-hGH in endurance-trained athletes increased lipolysis and fatty acid availability at rest and during and after exercise. r-hGH increased glucose production and uptake rates after exercise. The relevance of these effects for athletic performance is not known.     

Effects of lipolytic and antilipolytic agents on glucose transport in human fat cells.

The effects of lipolytic and antilipolytic agents on glucose transport and glycerol production in isolated human fat cells was investigated. Insulin and various adenylate cyclase inhibitors caused a dose-dependent stimulation of 3-O-methyl glucose transport. The maximum effects were 245 per cent and 100 per cent, respectively. The lipolytic agents isoprenaline, forskolin and dibutyryl cyclic AMP also caused dose-dependent stimulation of 3-O-methyl glucose transport, the maximum effect being about 100 per cent. Enprofylline counteracted the 3-O-methyl glucose transport-stimulating effect of both the lipolytic and antilipolytic agents but altered only the effect of antilipolytic agents on glycerol production. Enprofylline alone had no effect on 3-O-methyl glucose transport activity but stimulated glycerol production. It is on 3-O-methyl glucose transport activity but stimulated glycerol production. It is concluded that stimulation as well as inhibition of lipolysis at different steps in the lipolytic system is associated with acceleration of glucose transport in human fat cell which does not seem dependent upon the lipolysis rate.     

The impact of blood glucose levels on stimulated adrenocorticotropin hormone and growth hormone release in healthy subjects

Objective  In studies investigating the influence of glucose levels on the pituitary function the methods used have been variable and mainly focused on the change in function as a reaction to unphysiological low or high blood glucose levels. In the present study the impact of physiological and elevated blood glucose levels on adrenocorticotropin hormone (ACTH) and growth hormone release are investigated.
Design  The euglycaemic and hyperglycaemic clamp techniques were used to reach stable levels of 4, 8 and 12 mmol/l blood glucose levels. After a stabilization phase of 2 h, a corticotropin releasing hormone (CRH) or a growth hormone releasing hormone (GHRH) stimulation test was performed.
Subjects  Seven and eight healthy male volunteers, belonging to two groups, participated in this study.
Measurements  The area under the curve (AUC), peak values and time to peak of ACTH, cortisol and growth hormone were calculated to evaluate the response to the CRH and GHRH stimulation test.
Results  The peak values of ACTH, cortisol and growth hormone seemed to be the highest during the 4 mmol/l clamp sessions, compared with the 8 and 12 mmol/l clamps, although the differences were not statistically significant when analysed for every subject individually. The AUC and time to peak measurements were comparable during the three clamp procedures.
Conclusion  The pituitary reaction on CRH and GHRH was not significantly changed by various blood glucose levels.