PubMed Health⌕ Search

Biomedical subjects

N Møller

Publications and source records attributed to N Møller.

At least 19 recordsLinked to original sources
PubMed2006

Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failure.

OBJECTIVE: It is well known that chronic heart failure (CHF) is associated with insulin resistance and cachexia, but little is known about the underlying substrate metabolism. The present study was undertaken to identify disturbances of basal glucose, lipid and protein metabolism. DESIGN: We studied eight nondiabetic patients with CHF (ejection fraction 30 +/- 4%) and eight healthy controls. Protein metabolism (whole body and regional muscle fluxes) and total glucose turnover were isotopically assayed. Substrate oxidation were obtained by indirect calorimetry. The metabolic response to exercise was studied by bicycle ergometry exercise. RESULTS: Our data confirm that CHF patients have a decreased lean body mass. CHF patients are characterised by (i) decreased glucose oxidation [glucose oxidation (mg kg(-1) min(-1)): 1.25 +/- 0.09 (patients) vs. 1.55 +/- 0.09 (controls), P < 0.01] and muscle glucose uptake [a - v diff(glucose) (micromol L(-1)): -10 +/- 25 (patients) vs. 70 +/- 22 (controls), P < 0.01], (ii) elevated levels of free fatty acids (FFA) [FFA (mmol L(-1)): 0.72 +/- 0.05 (patients) vs. 0.48 +/- 0.03 (controls), P < 0.01] and 3-hydroxybutyrate and signs of elevated fat oxidation and muscle fat utilization [a - v diff(FFA) (mmol L(-1)): 0.12 +/- 0.02 (patients) vs. 0.05 +/- 0.01 (controls), P < 0.05] and (iii) elevated protein turnover and protein breakdown [phenylalanine flux (micromol kg(-1) h(-1)): 36.4 +/- 1.5 (patients) vs. 29.6 +/- 1.3 (controls), P < 0.01]. Patients had high circulating levels of noradrenaline, glucagon, and adiponectin, and low levels of ghrelin. We failed to observe any differences in metabolic responses between controls and patients during short-term exercise. CONCLUSIONS: In the basal fasting state patients with CHF are characterized by several metabolic abnormalities which may contribute to CHF pathophysiology and may provide a basis for targeted intervention.

Aged↗
PubMed2005

The effect of submaximal exercise on immuno- and bioassayable IGF-I activity in patients with GH-deficiency and healthy subjects.

OBJECTIVE: Growth hormone (GH) increases during exercise, but the response of the insulin-like growth factor (IGF) system has not been as definitive. Therefore, we investigated the effect of the exercise-induced GH response on the circulating IGF-system in GH-deficient (GHD) and intact adults. DESIGN: Eight GHD adults were studied on 2 occasions, with (+GH) and without (-GH) GH administered (0.4 IU) during exercise (45 min of cycle ergometer exercise at the lactate threshold). Eight age-matched controls were only studied on one occasion. Blood samples were drawn at baseline, during and post-exercise. IGFBP-3 proteolysis was measured by an in vitro proteolytic activity assay, IGF-I bioactivity by novel IGF-I kinase receptor activation assay (KIRA) and other hormones by immunoassay. RESULTS: GH administration to GHD adults resulted in a serum GH peak similar to the exercise-stimulated GH response in GH intact controls, but exercise had only a small impact on the IGF system. IGF-I concentration was lower in controls but was only significantly lower than the +GH day. Neither IGF-I nor -II levels changed over time. IGFBP-1 demonstrated a time effect (P<0.01) in all groups, and a time x group interaction (P<0.01) with a rise at 75 min post-exercise, which was greater in the GHD subjects than controls. IGFBP-2 and -3 increased significantly (P<0.01) over time in the GHD subjects, but not in the controls. No change in IGFBP-3 proteolysis or IGF-I bioactivity was found during exercise or recovery in either group. CONCLUSION: Submaximal exercise induced minor changes in IGFBP-1, -2 and -3, without affecting IGFBP-3 proteolysis and IGF-I bioavailability. Thus the metabolic status during submaximal exercise does not require a change in plasma IGF-I bioavailability. Administration of GH to GHD adults does not result in changes in proteolysis or bioavailability.

Adult↗
PubMed2005

Metabolic consequences of GH deficiency.

Patients with active acromegaly are insulin resistant and glucose intolerant, whereas children with GH deficiency are insulin sensitive and may develop fasting hypoglycemia. Surprisingly, however, hypopituitary adults with unsubstituted GH deficiency tend to be insulin resistant which may worsen during GH substitution. A unifying mechanism explaining insulin resistance in both conditions could be increased flux of free fatty acids (FFA) caused by visceral obesity (untrated GHDA) and enhanced lipid oxidation (GH substitution), respectively. During fasting, which may be considered the natural domain for the metabolic effects of GH, the induction of insulin resistance by GH is associated with enhanced lipid oxidation and protein conservation. In this particular context, insulin resistance appears to constitute a favorable metabolic adaptation. The problem is that GH substitution results in elevated circadian GH levels in non-fasting patients. The best way to address this challenge is to employ evening administration of GH and to tailor the dose. Insulin therapy may cause hypoglycemia, and GH substitution may cause hyperglycemia. Such untoward effects should be minimised by carefully monitoring the individual patient. It is also plausible that the long-term beneficial effects of GH on body composition will balance the insulin antagonistic effects on glucose metabolism.

Adult↗
PubMed2003

Additive effects of cortisol and growth hormone on regional and systemic lipolysis in humans.

Growth hormone (GH) and cortisol are important to ensure energy supplies during fasting and stress. In vitro experiments have raised the question whether GH and cortisol mutually potentiate lipolysis. In the present study, combined in vivo effects of GH and cortisol on adipose and muscle tissue were explored. Seven lean males were examined four times over 510 min. Microdialysis catheters were inserted in the vastus lateralis muscle and in the subcutaneous adipose tissue of the thigh and abdomen. A pancreatic-pituitary clamp was maintained with somatostatin infusion and replacement of GH, insulin, and glucagon at baseline levels. At t = 150 min, administration was performed of NaCl (I), a 2 microg.kg(-1).min(-1) hydrocortisone infusion (II), a 200-microg bolus of GH (III), or a combination of II and III (IV). Systemic free fatty acid (FFA) turnover was estimated by [9,10-3H]palmitate appearance. Circulating levels of glucose, insulin, and glucagon were comparable in I-IV. GH levels were similar in I and II (0.50 +/- 0.08 microg/l, mean +/- SE). Peak levels during III and IV were approximately 9 microg/l. Cortisol levels rose to approximately 900 nmol/l in II and IV. Systemic (i.e., palmitate fluxes, s-FFA, s-glycerol) and regional (interstitial adipose tissue and skeletal muscle) markers of lipolysis increased in response to both II and III. In IV, they were higher and equal to the isolated additive effects of the two hormones. In conclusion, we find that GH and cortisol stimulate systemic and regional lipolysis independently and in an additive manner when coadministered. On the basis of previous studies, we speculate that the mode of action is mediated though different pathways.

Abdomen↗
PubMed2003

Exercise, hormones, and body temperature. regulation and action of GH during exercise.

UNLABELLED: That physical exercise stimulates pituitary GH secretion has been known for forty years, but the underlying mechanisms as well as the physiological significance remain elusive. We have previously shown that the concomitant increase in core temperature is essential for the exercise-induced GH release, inasmuch as exercise performed at 4 C results in a suppression of GH secretion, whereas passive heating constitutes a potent stimulus for GH release. Moreover, studies in normal subjects show that GH stimulates sweat production and evaporative heat loss during heat exposure with and without exercise, whereas GH-deficiency is associated with reduced sweat secretion and increased heat storage during similar conditions. The neurotransmitters involved in GH secretion during exercise remain uncertain; we therefore investigated the putative role of ghrelin, which is a gut-derived endogenous ligand for the GHS receptor. We measured circulating ghrelin levels before during and after submaximal aerobic exercise in healthy subjects and GH-deficient patients. The circulating ghrelin levels were unchanged during and after exercise in all subjects. Growth hormone stimulates lipolysis and lipid oxidation during basal and fasting conditions and we recently investigated whether GH also regulates substrate metabolism during exercise. The design involved GH-deficient patients studied during exercise with and without GH administration as compared to untreated healthy subjects. Growth hormone predominantly stimulated the turnover of free fatty acids in the recovery phase after exercise. CONCLUSIONS: 1) the increase in GH release during exercise is associated with the concomitant increase in body temperature, 2) GH stimulates sweat secretion and heat evaporation during exercise, which seems to be of distinct physiological significance, 3) ghrelin is not involved in exercise-induced GH release, 4) the impact of GH on substrate metabolism during exercise includes increased FFA turnover.

Body Temperature↗
PubMed2002

Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans.

Cortisol's effects on lipid metabolism are controversial and may involve stimulation of both lipolysis and lipogenesis. This study was undertaken to define the role of physiological hypercortisolemia on systemic and regional lipolysis in humans. We investigated seven healthy young male volunteers after an overnight fast on two occasions by means of microdialysis and palmitate turnover in a placebo-controlled manner with a pancreatic pituitary clamp involving inhibition with somatostatin and substitution of growth hormone, glucagon, and insulin at basal levels. Hydrocortisone infusion increased circulating concentrations of cortisol (888 +/- 12 vs. 245 +/- 7 nmol/l). Interstitial glycerol concentrations rose in parallel in abdominal (327 +/- 35 vs. 156 +/- 30 micromol/l; P = 0.05) and femoral (178 +/- 28 vs. 91 +/- 22 micromol/l; P = 0.02) adipose tissue. Systemic [(3)H]palmitate turnover increased (165 +/- 17 vs. 92 +/- 24 micromol/min; P = 0.01). Levels of insulin, glucagon, and growth hormone were comparable. In conclusion, the present study unmistakably shows that cortisol in physiological concentrations is a potent stimulus of lipolysis and that this effect prevails equally in both femoral and abdominal adipose tissue.

Abdomen↗
PubMed2001

Skeletal muscle glucose uptake, glycogen synthase activity and GLUT 4 content during hypoglycaemia in type 1 diabetic subjects.

In healthy subjects, hypoglycaemia induces a profound 80% reduction in skeletal muscle glucose uptake and a similar suppression of glycogen synthase activity. The aim of this study was to examine the efficacy of this counterregulatory mechanism in type 1 diabetic subjects, who are especially prone to hypoglycaemic incidents. Nine type 1 diabetic male subjects were examined twice; during 120 min of hyperinsulinaemic (1.5 mU x kg(-1) x min(-1)) euglycaemia followed by (i) 240 min of graded hypoglycaemia (glucose nadir 2.8 mM) or (ii) 240 min of euglycaemia. At 345-360 min a muscle biopsy was taken and indirect calorimetry was performed at 210-240 and 320-340 min. The sensitivity of glycogen synthase to glucose-6-P was reduced by hypoglycaemia, as shown by an increase in A0.5 for glucose-6-P (at 0.07 mmol/L) from 0.21+/-0.02 to 0.28+/-0.03 mM (p=0.06). Likewise, the fractional velocity for glycogen synthase was reduced by 25%; i.e. from 20.8+/-2.0 to 15.5+/-1.4% (p<0.05). Total glucose disposal was decreased during hypoglycaemia (5.3+/-0.6 vs. 8.3+/-0.7 mg x kg(-1) x min(-1) (euglycaemia), n = 9; p<0.05), primarily due to a reduction of non-oxidative glucose disposal (2.7+/-0.3 vs. 5.1+/-0.6 mg x kg(-1) x min(-1) (euglycaemia), n=7; p<0.05). Forearm arteriovenous glucose differences were decreased by 50% in the hypoglycaemic situation (0.7+/-0.1 vs. 1.4+/-0.3 mmol/L (320-340 min)), and counterregulatory hormonal responses seemed less conspicuous than described in healthy subjects. We conclude that hypoglycaemia induces decrements of forearm glucose uptake and glycogen synthase activity in type 1 diabetic subjects. The study indicates a decreased magnitude of these responses, but this remains to be confirmed.

Adult↗
PubMed2001

Physiological levels of glucagon do not influence lipolysis in abdominal adipose tissue as assessed by microdialysis.

To determine whether glucagon stimulates lipolysis in adipose tissue, seven healthy young male volunteers were studied, with indwelling microdialysis catheters placed sc in abdominal adipose tissue. Subjects were studied three times: 1) during euglucagonemia (EG; glucagon infusion rate, 0.5 ng/kg.min); 2) during hyperglucagonemia (HG; (glucagon infusion rate, 1.5 ng/kg.min); and 3) during EG and a concomitant glucose infusion mimicking the glucose profile from the day of HG (EG+G). Somatostatin (450 microg/h) was infused to suppress hormonal secretion, and replacement doses of insulin and GH were administered. Sampling was done every 30 min for 420 min. Baseline circulating values of insulin, C-peptide, glucagon, GH, glycerol, and free fatty acids were comparable in all three conditions. During EG and EG+G, plasma glucagon was maintained at fasting level (20-40 ng/L); whereas, during HG, it increased (110-130 ng/L). Interstitial concentrations of glycerol were similar in the three conditions [30,870 +/- 5,946 (EG) vs. 31,074 +/- 7,092 (HG) vs. 29,451 +/- 6,217 (EG+G) micromol/L.120 min, P = 0.98]. Plasma glycerol (ANOVA, P = 0.5) and free fatty acids (ANOVA, P = 0.3) were comparable during the different glucagon challenges. We conclude that HG per se does not increase interstitial glycerol (and thus lipolysis) in abdominal sc adipose tissue; nor does modest hyperglycemia, during basal insulinemia and glucagonemia, influence indices of abdominal sc lipolysis.

Abdomen↗
PubMed2001

Continuation of growth hormone (GH) substitution during fasting in GH-deficient patients decreases urea excretion and conserves protein synthesis.

The consequences of GH deficiency during conditions in which endogenous GH release is acutely stimulated are largely unknown. Short-term fasting constitutes a robust GH stimulus, but the metabolic significance of GH during fasting is uncertain. To address both of these issues, we therefore evaluated the effect of GH on substrate metabolism during fasting in adults with GH deficiency. Seven hypopituitary GH-deficient patients were each studied twice during a 40-h fast: once with GH replacement continued and once with GH discontinued during the fast. After 40 h of fasting, protein synthesis and turnover were higher with than without GH replacement [phenylalanine incorporation (micromol/kg fat free mass/h): 36.6 +/- 1.2 (GH) vs. 32.8 +/- 1.4, P < 0.05; phenylalanine flux (micromol/kg fat free mass/h): 41.3 +/- 1.0 (GH) vs. 38.0 +/- 1.8, P < 0.05]. During continued GH replacement, urea excretion decreased during nighttime [urea excretion (mmol/24 h): 269 +/- 51 (GH) vs. 390 +/- 69, P < 0.05], and a significant decline in urea-N synthesis rate was found [urea-N synthesis rate (mmol/h): 14.7 +/- 1.6 (GH) vs. 21.1 +/- 2.2, P < 0.01]. GH replacement was associated with increased lipid oxidation [lipid oxidation (mg/kg per min): 0.91 +/- 0.07 (GH) vs. 0.70 +/- 0.03, P < 0.05]. Finally, continuation of GH induced moderate elevations in plasma glucose levels without significant changes in total glucose turnover or oxidation. In summary, continued GH substitution during fasting conserves nitrogen, which involves stimulation or maintenance of protein synthesis. Our data support the importance of GH replacement in hypopituitary adults.

Adult↗
PubMed2001

The protein-retaining effects of growth hormone during fasting involve inhibition of muscle-protein breakdown.

The metabolic response to fasting involves a series of hormonal and metabolic adaptations leading to protein conservation. An increase in the serum level of growth hormone (GH) during fasting has been well substantiated. The present study was designed to test the hypothesis that GH may be a principal mediator of protein conservation during fasting and to assess the underlying mechanisms. Eight normal subjects were examined on four occasions: 1) in the basal postabsorptive state (basal), 2) after 40 h of fasting (fast), 3) after 40 h of fasting with somatostatin suppression of GH (fast-GH), and 4) after 40 h of fasting with suppression of GH and exogenous GH replacement (fast+GH). The two somatostatin experiments were identical in terms of hormone replacement (except for GH), meaning that somatostatin, insulin, glucagon and GH were administered for 28 h; during the last 4 h, substrate metabolism was investigated. Compared with the GH administration protocol, IGF-I and free IGF-I decreased 35 and 70%, respectively, during fasting without GH. Urinary urea excretion and serum urea increased when participants fasted without GH (urea excretion: basal 392 +/- 44, fast 440 +/- 32, fast-GH 609 +/- 76, and fast+GH 408 +/- 36 mmol/24 h, P < 0.05; serum urea: basal 4.6 +/- 0.1, fast 6.2 +/- 0.1, fast-GH 7.0 +/- 0.2, and fast+GH 4.3 +/- 0.2 mmol/1, P < 0.01). There was a net release of phenylalanine across the forearm, and the negative phenylalanine balance was higher during fasting with GH suppression (balance: basal 9 +/- 3, fast 15 +/- 6, fast-GH 17 +/- 4, and fast+GH 11 +/- 5 nmol/min, P < 0.05). Muscle-protein breakdown was increased among participants who fasted without GH (phenylalanine rate of appearance: basal 17 +/- 4, fast 26 +/- 9, fast-GH 33 +/- 7, fast+GH 25 +/- 6 nmol/min, P < 0.05). Levels of free fatty acids and oxidation of lipid decreased during fasting without GH (P < 0.01). In summary, we find that suppression of GH during fasting leads to a 50% increase in urea-nitrogen excretion, together with an increased net release and appearance rate of phenylalanine across the forearm. These results demonstrate that GH-possibly by maintenance of circulating concentrations of free IGF-I--is a decisive component of protein conservation during fasting and provide evidence that the underlying mechanism involves a decrease in muscle protein breakdown.

Adult↗
PubMed2001

Pharmacological antilipolysis restores insulin sensitivity during growth hormone exposure.

Stimulation of lipolysis and the induction of resistance to insulin's actions on glucose metabolism are well-recognized effects of growth hormone (GH). To evaluate whether these two features are causally linked, we studied the impact of pharmacologically induced antilipolysis in seven GH-deficient patients (mean [+/- SE] age 37 +/- 4 years). Each subject was studied under four different conditions: during continuation of GH replacement alone (A), after discontinuation of GH replacement for 2 days (B), after GH replacement and short-term coadministration of acipimox (250 mg, p.o., b.i.d., for 2 days) (C), and after administration of acipimox alone (D). At the end of each study, total and regional substrate metabolisms were assessed in the basal state and after a 3-h hyperinsulinemic/euglycemic clamp. Serum levels of free fatty acids (FFAs) were elevated with GH alone (A) and suppressed with acipimox (C and D). Basal rates of lipid oxidation were highest with GH alone (A), and suppressed by 50% with acipimox (B versus D, P < 0.01; A versus C, P < 0.05). Basal glucose oxidation rates were lowest with GH alone (A) and highest with acipimox (C and D) (P = 0.01). Insulin-stimulated rates of total glucose turnover were significantly lower with GH alone as compared with all other conditions (P = 0.004). Insulin sensitivity as assessed by the M value (rate of glucose infusion) was reduced with GH alone as compared with all other conditions (M value in mg. kg(-1). min(-1): GH alone [A], 2.55 +/- 0.64; discontinuation of GH [B], 4.01 +/- 0.70; GH plus acipimox [C], 3.96 +/- 1.34; acipimox alone [D], 4.96 +/- 0.91; P < 0.01). During pharmacological antilipolysis, GH did not significantly influence insulin sensitivity (C versus D; P = 0.19). From our results, we reached the following conclusions: 1) Our data strongly suggest that the insulin antagonistic actions of GH on glucose metabolism are causally linked to the concomitant activation of lipolysis. 2) In addition, GH may induce residual insulin resistance through non-FFA-dependent mechanisms. 3) The cellular and molecular mechanisms subserving the insulin antagonistic effects of GH remain to be elucidated.

Adult↗
PubMed2000

The kidney is an important site for in vivo phenylalanine-to-tyrosine conversion in adult humans: A metabolic role of the kidney.

Synthesis of Tyr in the human body occurs by hydroxylation of the indispensable amino acid Phe. Until now, it was believed that in humans, this process was restricted to the liver, but we provide compelling evidence of production of Tyr from Phe in the kidney. To determine whether the human kidney produces Tyr, we measured Tyr balance, the Tyr appearance rate, and the Phe-to-Tyr conversion in 12 healthy human subjects by using [(15)N]Phe and [(2)H(4)]Tyr as tracers. Renal plasma flow was measured by using paraaminohippurate, and sampling from the femoral artery and renal veins was performed. The results were compared with those obtained in 12 control subjects undergoing hepatic vein catheterization and infusion of identical tracers. In all 12 subjects, there was a net uptake of Phe by the kidney (2.2 +/- 1.2 micromol/min), whereas Tyr was released (5.3 +/- 1.5 micromol/min). In contrast, there was a net uptake of both Phe (9.5 +/- 1.2 micromol/min) and Tyr (14.3 +/- 1.3 micromol/min) by the splanchnic bed. Phe conversion to Tyr occurred at a rate of 5.2 +/- 1.2 micromol/min in kidney and 3.0 +/- 0.7 micromol/min in the splanchnic bed. The kidney contributed a substantial amount of Tyr to the systemic circulation where the splanchnic bed was a net remover of Tyr. Our results demonstrate that the kidney is the major donor of Tyr to the systemic circulation by its conversion of Phe to Tyr. This observation may have important clinical implications for patients with both renal and hepatic disease, who may be at risk of Phe overloading and Tyr deficiency, and it should be considered when parenteral or enteral nutrients are administered rich in Phe and low in Tyr.

Adult↗
PubMed2000

Effects of growth hormone administration on protein dynamics and substrate metabolism during 4 weeks of dietary restriction in obese women.

OBJECTIVE: Treatment of obesity with very low calorie diet (VLCD) is complicated by protein loss. We evaluated the effects of coadministration of GH on protein turnover, substrate metabolism, and body composition in VLCD treated obesity. DESIGN AND PATIENTS: Fifteen obese women underwent 4 weeks of very low calorie diet (VLCD) in parallel with GH treatment (n = 7) or placebo (n = 8). MEASUREMENTS: Protein metabolism and total glucose turnover were isotopically assayed. Plasma concentrations of amino acids were determined by an HPLC system. Estimated rates of lipid and glucose oxidation were obtained by indirect calorimetry. Fat free mass was determined by DEXA-scan. RESULTS: Protein breakdown decreased in both groups (tyrosine flux micromol/h): -12% +/- 3 (GH) vs. - 9% +/- 3 (placebo)). Phenylalanine degradation in relation to phenylalanine concentration decreased by 9% in the GH group, whereas an increase of 8% was observed in the placebo group (P = 0.1). Plasma concentrations of several amino acids were significantly decreased in the placebo group, while urea excretion decreased in the GH group. A decrease in FFM was found in placebo treated patients (2.14% +/- 1.9 (GH) vs. - 3.54% +/- 1.6 (placebo), P < 0.05). Rates of lipid oxidation tended to be increased by GH treatment (lipid oxidation (mg/minutes): 79.7 +/- 5.9 (GH) vs. 64.6 +/- 5.9 (placebo), P = 0.1). CONCLUSION: During dietary restriction GH primarily seems to conserve protein by a reduced hepatic degradation of amino acids.

Adult↗
PubMed2000

Effects of oral glucose on systemic glucose metabolism during hyperinsulinemic hypoglycemia in normal man.

The widespread use of oral glucose in the treatment of hypoglycemia is mainly empirically based, and little is known about the time lag and subsequent magnitude of effects following its administration. To define the systemic impact and time course of effects following oral glucose during hypoglycemia, we investigated 7 healthy young men twice. On both occasions, a 6-hour hyperinsulinemic (1.5 mU/kg/min)-hypoglycemic clamp was performed to ensure similar plasma glucose profiles during a stepwise decrease toward a nadir less than 50 mg/100 mL after 3 hours. On the first occasion, subjects ingested 40 g glucose and 4 g 3-ortho-methylglucose ([3-OMG] to trace glucose absorption) dissolved in 400 mL tap water after 3.5 hours. The second examination was identical except for the omission of 40 g oral glucose, and glucose levels were clamped at hypoglycemic concentrations similar to those recorded on the first examination. Plasma glucose curves were superimposable, and all participants reached a nadir less than 50 mg/100 mL. Similar increases in growth hormone (GH) and glucagon were observed in both situations. The glucose infusion rates (GIRs) were lower after oral glucose, with the difference starting after 5 to 10 minutes, being statistically significant after 20 minutes, and reaching a maximum of 8.5 +/- 1.6 mg/kg/min after 40 minutes. Circulating 3-OMG increased after 20 minutes. In both situations, infusion of insulin resulted in insulin levels of approximately 150 microU/mL and a suppression of C-peptide levels from 2.0 to 1.1 nmol/L (P < .01). After glucose ingestion, both serum C-peptide and glucagon-like peptide-1 (GLP-1) increased (C-peptide from 1.1 +/- 0.05 to 1.4 +/- 0.05 nmol/L and GLP-1 from 3.2 +/- 0.8 to 18.1 +/- 3.3 pmol/L), in contrast to the situation without oral glucose (P < .05). Isotopically determined glucose turnover was similar. In conclusion, our data suggest that oral glucose affects systemic glucose metabolism rapidly after 5 to 10 minutes. Quantitatively, the immediate impact is relatively small, with the gross impact observed after approximately 40 minutes. Future studies aiming to identify therapeutic oral agents with prompt effect seem warranted.

Administration, Oral↗
PubMed2000

Continuation of growth hormone (GH) therapy in GH-deficient patients during transition from childhood to adulthood: impact on insulin sensitivity and substrate metabolism.

The appropriate management of GH-deficient patients during transition from childhood to adulthood has not been reported in controlled trials, even though there is evidence to suggest that this phase is associated with specific problems in relation to GH sensitivity. An issue of particular interest is the impact of GH substitution on insulin sensitivity, which normally declines during puberty. We, therefore, evaluated insulin sensitivity (euglycemic glucose clamp) and substrate metabolism in 18 GH-deficient patients (6 females and 12 males; age, 20 +/- 1 yr; body mass index, 25 +/- 1 kg/m2) in a placebo-controlled, parallel study. Measurements were made at baseline, where all patients were on their regular GH replacement, after 12 months of either continued GH (0.018 +/- 0.001 mg/kg day) or placebo, and finally after 12 months of open phase GH therapy (0.016 mg/kg x day). Before study entry GH deficiency was reconfirmed by a stimulation test. During the double-blind phase, insulin sensitivity and fat mass tended to increase in the placebo group [deltaM-value (mg/kg x min), -0.7 +/- 1.1 (GH) vs. 1.3 +/- 0.8 (placebo), P = 0.18; deltaTBF (kg), 0.9 +/- 1.2 (GH) vs. 4.4 +/- 1.6 (placebo), P = 0.1]. Rates of lipid oxidation decreased [delta lipid oxidation (mg/kg x min), 0.02 +/- 0.14 (GH) vs. -0.32 +/- 0.13 (placebo), P < 0.05], whereas glucose oxidation increased in the placebo-treated group (P < 0.05). In the open phase, a decrease in insulin sensitivity was found in the former placebo group, although they lost body fat and increased fat-free mass [M-value (mg/kg x min), 5.1 +/- 0.7 (placebo) vs. 3.4 +/- 1.0 (open), P = 0.09]. In the group randomized to continued GH treatment almost all hormonal and metabolic parameters remained unchanged during the study. In conclusion, 1) discontinuation of GH therapy for 1 yr in adolescent patients induces fat accumulation without compromising insulin sensitivity; and 2) the beneficial effects of continued GH treatment on body composition in terms of decrease in fat mass and increase in fat-free mass does not fully balance the direct insulin antagonistic effects.

3-Hydroxybutyric Acid↗
PubMed2000

Effects of leptin on basal and FSH stimulated steroidogenesis in human granulosa luteal cells.

BACKGROUND: Body weight influences fertility and studies in mice have indicated that leptin is one of the mediators of this effect. Leptin is believed to centrally stimulate the hypothalamic-pituitary axis resulting in increased gonadotropin release. Moreover, leptin is present in follicular fluid and the receptor is expressed in the human ovary. The aim of this study was to evaluate the direct effect of leptin on cultured human granulosa cell steroidogenesis. METHODS: Granulosa cells were obtained in connection with IVF procedures, and then cultured in a serum-free medium containing androstenedione (1 microM) for a total of 4 days. After 2 days of culture the medium was changed and the hormones under study were added. We tested the effect of leptin (1, 20, 100 ng/ml) on basal, FSH (10-100 ng/ml), and FSH (10-100 ng/ml)+IGF-I (30 ng/ml) stimulated steroidogenesis. RESULTS: Leptin (20 ng/ml and 100 ng/ml) significantly reduced basal and FSH-stimulated estradiol secretion (p<0.05). Basal and FSH (10 and 30 ng/ml) stimulated progesterone production was significantly inhibited by leptin 20 ng/ml, whereas leptin 100 ng/ml significantly reduced basal but not FSH stimulated progesterone production. Finally, steroidogenesis stimulated by IGF-I alone and in combination with FSH was not influenced by leptin. CONCLUSION: These results suggest that leptin acts directly to inhibit basal and FSH stimulated estradiol and progesterone production in cultured human granulosa cells. This raises the possibility that high circulating leptin levels as seen in obese women may compromise fertility through peripheral mechanisms.

Body Weight↗