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Niels Møller

Publications and source records attributed to Niels Møller.

36 records · Page 2Linked to original sources
PubMed2003

The role of growth hormone in the regulation of protein metabolism with particular reference to conditions of fasting.

Growth hormone (GH) has potent protein anabolic actions, as evidenced by a significant decrease in lean body mass and muscle mass in chronic GH deficiency, and vice versa in patients with acromegaly. Depending on the prevailing physiological conditions and on which tissues and which proteins are under examination, the mechanisms involved include both stimulation of protein synthesis and restriction of protein breakdown. Apart from the possible direct effects of GH on protein dynamics, a number of additional anabolic agents, such as insulin, insulin-like growth factor-I and free fatty acids (FFA), are activated. Some of the most recent studies in the field have demonstrated a decisive role of stimulation of lipolysis and high circulating levels of FFA in orchestrating the maintenance of the protein pool of the body.

Animals↗
PubMed2003

Effects of ageing on insulin secretion and action.

One of the many conditions associated with ageing is type 2 diabetes mellitus, the prevalence of which increases from 20-30 years of age onwards. In many cases, type 2 diabetes mellitus is caused by the combination of insulin resistance and poor insulin secretion. Insulin resistance is also a risk factor associated with other disorders, in particular cardiovascular disease. Physiological changes associated with ageing, such as changes in body composition, decreased physical fitness, changes in hormones, and the secondary effects of high levels of free fatty acids and glucose, may also contribute to the impairment of insulin secretion and action. In this review, the effects of ageing on the secretion and action of insulin will be highlighted.

Aging↗
PubMed2003

Splanchnic release of ghrelin in humans.

Ghrelin is a novel polypeptide identified in rat stomach, and it increases GH release, gastric motility, and appetite and modulates many other organ functions. It has been reported that ghrelin may be released from a variety of other tissues, but the absolute contribution of the splanchnic bed remains to be defined. We quantified the splanchnic output of ghrelin in 22 healthy people after an overnight fast, with indwelling catheters in the femoral artery and hepatic vein. Splanchnic ghrelin output was calculated by multiplying veno-arterial difference in ghrelin concentration with splanchnic plasma flow (measured by indicator dye dilution technique). Plasma ghrelin was measured using (125)I-labeled ghrelin and rabbit polyclonal antibody raised against octanoylated human ghrelin. Ghrelin concentrations in the artery and in the hepatic veins were 960 +/- 82 pg/ml and 1102 +/- 90 pg/ml (P < 0.001), respectively. The veno-arterial concentration difference was 143 +/- 38 pg/ml, amounting to 15% of the arterial concentration. The splanchnic output of ghrelin was 141 +/- 43 ng/min (P < 0.003). Assuming that the half-life of ghrelin is less than 60 min, the splanchnic output would explain the entire amount of circulating ghrelin in the postabsorptive state. We conclude that a substantial amount of ghrelin is being released from the splanchnic bed in the postabsorptive state in healthy human subjects and that splanchnic bed is the major source of circulating ghrelin in humans.

Adult↗
PubMed2003

Hyperthyroidism is associated with suppressed circulating ghrelin levels.

Ghrelin stimulates GH secretion as well as appetite and food intake. To explore whether ghrelin is involved in the regulation of appetite and body weight in hyperthyroidism, circulating ghrelin levels were measured in nine hyperthyroid patients before and after medical treatment and compared with those in eight healthy control subjects. All participants were studied in the postabsorptive state and during a 3-h euglycemic hyperinsulinemic clamp. Before treatment the patients had 3- to 5-fold elevations of T(3), and during treatment the patients gained 5 kg of body weight. Ghrelin levels were decreased in hyperthyroidism both in the fasting state (hyperthyroid, 1080 +/- 195 pg/ml; euthyroid, 1480 +/- 215 pg/ml; P = 0.03) and during clamp (hyperthyroid, 833 +/- 150 pg/ml; euthyroid, 1210 +/- 180 pg/m; P = 0.02). After treatment, ghrelin levels did not differ from those in control subjects. In all three study groups the clamp significantly reduced ghrelin levels compared with fasting levels. In conclusion, ghrelin levels are reduced in hyperthyroidism and become normalized by medical antithyroid treatment. Hyperinsulinemia suppresses ghrelin regardless of thyroid status. Ghrelin is not a primary stimulator of appetite and food intake in hyperthyroidism, and the mechanisms underlying the suppressive effect of hyperthyroidism on ghrelin secretion remain unclear.

Adult↗
PubMed2003

The effect of growth hormone on the insulin-like growth factor system during fasting.

The present study investigates the possible stimulatory effect of endogenous GH on IGF and IGF-binding protein (IGFBP) levels during fasting. Eight normal subjects were examined on four occasions: 1) in the basal postabsorptive state; 2) after 40 h of fasting; 3) after 40 h of fasting with somatostatin suppression of GH; and 4) after 40 h of fasting with suppression of GH and exogenous GH replacement. The two somatostatin experiments were identical in terms of hormone replacement (except for GH). Short-term fasting led to a 50% reduction in free IGF-I. The reduction in free IGF-I was paralleled by an increase in IGFBP-1, an increase in the complex formation of IGFBP-1 and IGF-I, and a modest reduction in IGFBP-3 proteolysis. GH deprivation during fasting led to a 35% reduction in total IGF-I and a 70% reduction in free IGF-I. GH replacement increased free and total IGF-I to levels similar to those observed during plain fasting and decreased IGFBP-1, however, without affecting IGFBP-1-bound IGF-I. Finally, IGFBP-3 proteolysis was slightly increased by GH replacement. In conclusion, the major new finding of the present study is that the GH hypersecretion seen during short-term fasting is not merely secondary to a reduction in IGF bioactivity.

Adult↗
PubMed2003

The decisive role of free fatty acids for protein conservation during fasting in humans with and without growth hormone.

During fasting, a lack of GH increases protein loss by close to 50%, but the underlying mechanisms remain uncertain. The present study tests the hypothesis that the anabolic actions of GH depend on mobilization of lipids. Seven normal subjects were examined on four occasions during a 37-h fast with infusion of somatostatin, insulin, and glucagon for the final 15 h: 1) with GH replacement, 2) with GH replacement and antilipolysis with acipimox, 3) without GH and with antilipolysis, and 4) with GH replacement, antilipolysis, and infusion of intralipid. Urinary urea excretion, serum urea concentrations, and muscle protein breakdown (assessed by labeled phenylalanine) increased by almost 50% during fasting with suppression of lipolysis. Addition of GH during fasting with antilipolysis did not influence indexes of protein degradation, whereas restoration of high FFA levels regenerated proportionally low concentrations of urea and decreased whole body protein degradation (phenylalanine to tyrosine conversion) by 10-15%, but failed to affect muscle protein metabolism. Thus, the present data provide strong evidence that FFA are important protein-sparing agents during fasting. The finding that inhibition of lipolysis eliminates the ability of GH to restrict fasting protein loss indicates that stimulation of lipolysis is the principal protein-conserving mechanism of GH.

Adult↗
PubMed2002

[Scurvy and adrenal insufficiency].

We describe a case of scurvy in a 32-year-old woman. The disease was associated with bilateral tumours of the quadriceps muscles and malignancy was considered. Adrenal insufficiency was also diagnosed. All abnormalities subsided in response to vitamin C therapy. It is unknown whether there is a causal link between the two diseases, but evaluation of adrenal function seems justified in future cases of scurvy.

Adrenal Insufficiency↗
PubMed2002

Effects of GH on protein metabolism during dietary restriction in man.

The metabolic response to dietary restriction 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. GH has potent protein anabolic actions, as evidenced by a significant decrease in lean body mass and muscle mass in chronic GH deficiency, and vice versa in patients with acromegaly. The present review outlines current knowledge about the role of GH in the metabolic response to fasting, with particular reference to the effects on protein metabolism. Physiological bursts of GH secretion seem to be of seminal importance for the regulation of protein conservation during fasting. Apart from the possible direct effects of GH on protein dynamics, a number of additional anabolic agents, such as insulin, insulin-like growth factor-I, and free fatty acids (FFAs), are activated. Taken together the effects of GH on protein metabolism seem to include both stimulation of protein synthesis and inhibition of breakdown, depending on the nature of GH administration, which tissues are being studied, and on the physiological conditions of the subjects.

Caloric Restriction↗
PubMed2002

Effects of lowering circulating free fatty acid levels on protein metabolism in adult growth hormone deficient patients.

Our study was conducted to define the roles of lowering circulating free fatty acids (FFA) and of growth hormone (GH) replacement on protein metabolism in GH deficient patients. To isolate the specific effects of FFA and GH we studied seven adult subjects with GH deficiency four times: (A) with administration of GH and Acipimox (an inhibitor of lipolysis), (B) with GH, without Acipimox, (C) without GH, with Acipimox and (D) without either. Each study included a 3 h basal period and a 3 h euglycemic clamp. Amino acid metabolism was assessed by stable isotope dilution technique at the whole body level and across the forearm. Overall, we saw no intervention effect on protein metabolism, but when the two situations in which Acipimox was given were combined, Acipimox decreased basal plasma FFA concentrations by 75% and increased serum urea concentrations by 20%, whole body appearance rates (reflecting protein degradation) of phenylalanine (by 7%) and tyrosine (by 11%) and protein synthesis rates for phenylalanine (by 7%), whereas phenylalanine-to-tyrosine conversion was unaffected. Acipimox more than doubled net forearm phenylalanine release during the clamp and increased basal forearm phenylalanine disappearance (reflecting muscle protein synthesis). During the clamp whole body amino acid fluxes and phenylalanine-to-tyrosine conversion decreased together with a decrease in forearm protein breakdown. GH replacement did not affect any of these metabolic parameters. Although we failed to show any role for GH, the results show that lowering of FFA concentrations with Acipimox has pronounced effects on protein metabolism, including increased whole body and forearm protein breakdown, together with increased protein synthesis systemically and locally in the forearm. The increase in serum urea and a doubling of net forearm phenylalanine release after lowering of FFA strongly indicate that the overall effect is catabolic and supports a pivotal protein conserving role of lipids.

Adult↗
PubMed2002

Preferential stimulation of abdominal subcutaneous lipolysis after prednisolone exposure in humans.

OBJECTIVE: The role of cortisol in the regulation of lipolysis is not clear. This study was undertaken to explore whether a standard dose of prednisolone for 1 week would influence lipolysis in abdominal and femoral tissue. RESEARCH METHODS AND PROCEDURES: We used the microdialysis technique, the forearm technique, and indirect calorimetry, in the fasting state, after 1 week of treatment with prednisolone (30 mg daily) or placebo. Eight healthy young men (age: 25 +/- 3 years; height: 181 +/- 1 cm; body mass index [BMI]: 23.3 +/- 0.7 kg/m(2)) were studied. RESULTS: Treatment with prednisolone induced insulin resistance (Homeostasis Model Assessment index: placebo vs. prednisolone: 7.15 +/- 1.63 vs. 17.00 +/- 14.26, p = 0.03), hyperinsulinemia (p = 0.01), and hyperglucagonemia (p = 0.001), whereas growth hormone concentrations were unaffected. Abdominal adipose tissue interstitial glycerol was increased during treatment with prednisolone in the face of significant hyperinsulinemia, although it barely reached statistical significance (p = 0.06). At the femoral adipose tissue depot, no difference in lipolysis was found. Arterial and venous free fatty acids (FFA) were comparable in the two situations, whereas the arteriovenous difference across the forearm was significantly decreased during treatment with prednisolone, indicating increased uptake, or decreased release of FFA. Energy expenditure (p = 0.3), respiratory quotient (p = 0.9), glucose oxidation (p = 0.9), lipid oxidation (p = 1.0), and protein oxidation (p = 0.1) were unaltered on the 2 study days. DISCUSSION: Short-term treatment with a standard dose of corticosteroids induces increased abdominal adipose tissue lipolysis, as well as hyperinsulinemia, hyperglucagonemia, and insulin resistance.

Abdomen↗
PubMed2002

Age dimorphism in the association between growth-hormone status and the respiratory quotient.

OBJECTIVE: To investigate the impact of age on the association between the respiratory quotient (RQ) and growth-hormone (GH) secretion and to investigate the acute lipolytic response to an exogenous GH bolus. RESEARCH METHODS AND PROCEDURES: A cross-sectional study of 36 non-obese healthy subjects (18 women and 18 men) from two age groups was used: "younger" (mean age, 29.5 years; range, 27 to 34 years) and "older" (mean age, 50.8 years; range, 47 to 59 years). Endogenous GH secretion by means of deconvolution analysis of 24-hour serum GH concentrations was measured every 20 minutes. Resting RQ was measured after a 12-hour overnight fast. The lipolytic response to an intravenous exogenous GH bolus (200 microg) was assessed by measuring serum levels of free fatty acids as well as changes in RQ. Additional measurements included body composition (regional computed tomography scan and DXA) and physical fitness (VO(2)max). RESULTS: Resting RQ did not differ between the two age groups: 0.81 +/- 0.01 (young) vs. 0.82 +/- 0.01 (older; not significant). Several estimates of GH release correlated positively with RQ in the younger group, whereas a negative correlation was detected in the older subjects [GH production rate (microg/liter x kg) vs. RQ: r = 0.62, p < 0.01 (younger); r = -0.53; p = 0.02 (older)]. By regression analysis, 52% to 58% of the variation in RQ could be explained by GH status. After an exogenous GH bolus, the incremental response in nonesterified fatty acid was slightly higher in younger individuals (p = 0.09). DISCUSSION: Resting RQ is significantly correlated with GH status. This association is positive in younger individuals and negative in older individuals. The lipolytic response to exogenous GH is moderately higher in younger compared with older individuals. GH status should be taken into account when investigating the residual variation in RQ.

Adult↗
PubMed2002

Ghrelin immunoreactivity in human plasma is suppressed by somatostatin.

OBJECTIVE: Ghrelin was recently identified as a specific endogenous ligand for the growth hormone secretagogue receptor (GHS-R). This new hormone was isolated from rat and human stomach and was reported to circulate in human plasma, but the regulation and physiological significance of ghrelin in humans have not been clarified. The present study was undertaken to test the following hypotheses: (1) prolonged fasting, which is known to stimulate GH secretion, is associated with changes in ghrelin immunoreactivity; (2) somatostatin in the systemic circulation regulates ghrelin secretion; and (3) GH affects ghrelin levels. DESIGN AND PATIENTS: The study population included normal subjects investigated on three occasions (fasting alone, fasting and somatostatin infusion +/- GH); GH-deficient adults investigated after 12 and 36 h of fasting +/- GH, as well as patients with active acromegaly before and after somatostatin analogue treatment. RESULTS: Somatostatin infusion lowered ghrelin levels 70-80% (P < 0.0001), whereas continued fasting +/- GH did not significantly affect ghrelin levels. In active acromegaly, suppression of plasma ghrelin levels was recorded after a single subcutaneous octreotide injection as well as during prolonged administration of slow-release octreotide. CONCLUSIONS: (1) Amplification of GH release during prolonged fasting is not caused by an increase in ghrelin immunoreactivity, (2) systemic somatostatin suppresses plasma ghrelin levels independently of GH status, and (3) the feasibility of measuring ghrelin in the circulation provides an opportunity for studying the interaction between hormones and nutrition.

Acromegaly↗
PubMed2002

Elevated regional lipolysis in hyperthyroidism.

Hyperthyroidism is characterized by increased levels of circulating free fatty acids (FFA) and increased lipid oxidation, but it is uncertain which regional fat depots contribute. The present study was designed to define the participation of femoral and abdominal fat stores in the overall stimulation of lipolysis in hyperthyroidism in the basal state and during insulin stimulation. We studied nine women with newly diagnosed hyperthyroidism (HT) and after (euthyroidism, ET) medical treatment with methimazol and compared with eight control subjects (CTR). All subjects were studied in the postabsorptive state and during a 3-h hyperinsulinemic euglycemic clamp with microdialysis catheters sc in the abdominal and femoral adipose tissue. Before treatment, patients had elevated circulating concentrations of triiodthyronine, FFA, and glycerol. Levels of interstitial glycerol ( micro mol/liter) in abdominal adipose tissue [485 +/- 24 (HT), 226 +/- 20 (ET) (P < 0.001), 265 +/- 34 (CTR) (P < 0.001)] and in femoral adipose tissue [468 +/- 41(HT), 245 +/- 29 (ET) (P < 0.01), 278 +/- 31(CTR) (P < 0.005)] were elevated in the basal hyperthyroid state, and these differences prevailed during the glucose clamp [230 +/- 23 (HT), 113 +/- 13 (ET) (P < 0.01), 132 +/- 22(CTR) (P < 0.01) and 303 +/- 39 (HT), 122 +/- 15 (ET) (P < 0.01), 166 +/- 21(CTR) (P < 0.01)]. These results suggest that femoral and abdominal adipose tissue contribute equally to the excessive rate of lipolysis in hyperthyroidism and that both tissues are resistant to the actions of insulin.

Abdomen↗
PubMed2002

The effect of long-term pharmacological antilipolysis on substrate metabolism in growth hormone (GH)-substituted GH-deficient adults.

The lipolytic properties of GH are essential for the acute effects on glucose metabolism and insulin sensitivity, whereas its more long-term impact on substrate metabolism is uncertain. The aim of the study was to evaluate the influence of pharmacological antilipolysis on substrate metabolism during constant and continued GH exposure. Seven adult GH-deficient (GHD) patients were studied twice in a double-blind randomized order: 1) after 4 wk of acipimox treatment (250 mg, orally, three times daily) and 2) after 4 wk of placebo treatment. Daily GH replacement was continued throughout both study periods. At the end of each period glucose and lipid oxidation rates were assessed by indirect calorimetry, and the protein oxidation rate was estimated by urinary excretion of urea. Endogenous glucose production and whole body protein metabolism were assessed by isotope dilution techniques using tritiated glucose and stable phenylalanine and tyrosine isotopes, respectively. GH and IGF-I levels were not different between periods, whereas FFA and glycerol levels were distinctly suppressed after 4 wk of pharmacological antilipolysis [FFA, 256 +/- 63 (acipimox) vs. 596 +/- 69 (placebo) micromol/liter; P = 0.001]. Likewise, plasma levels of total and low density lipoprotein cholesterol as well as triglycerides were significantly reduced after acipimox. Despite this, lipid oxidation rates were identical at the end of the two treatment periods [589 +/- 106 (acipimox) vs. 626 +/- 111 (placebo) kcal/24 h; P = 0.698]. The total and oxidative rates of glucose as well as protein oxidation and urea excretion were identical at the end of the two treatment periods (P > 0.05). Phenylalanine flux, a measure of protein turnover, was increased [34.62 +/- 1.83 (acipimox) vs. 33.15 +/- 1.61 (placebo) micromol/kg.h; P = 0.049] as was phenylalanine incorporation into protein, a measure of protein synthesis [30.79 +/- 1.67 (acipimox) vs. 28.97 +/- 1.51 (placebo) micromol/kg.h; P = 0.035]. The following conclusions were reached: 1) prolonged antilipolysis by means of acipimox stimulates protein turnover without affecting net protein balance; and 2) acipimox in combination with constant GH exposure results in sustained suppression of circulating levels of FFA, glycerol, and triglycerides without a reduction in the rate of lipid oxidation. The site and origin of lipid fuels for oxidation during suppression of lipolysis remain to be determined.

Adult↗
PubMed2002

Plasma ghrelin levels during exercise in healthy subjects and in growth hormone-deficient patients.

OBJECTIVE: To characterise plasma levels of the recently identified endogenous ligand for the GH secretagogue receptor (ghrelin) during submaximal aerobic exercise in healthy adults and in GH-deficient adults. DESIGN: Eight healthy males (mean+/-s.e. age, 40.8+/-2.9 years) and eight hypopituitary males with verified GH deficiency (mean+/-s.e. age, 40.8+/-4.7 years) underwent a baseline test of their peak aerobic capacity (VO(2) peak) and lactate threshold (LT) on a cycle ergometer, as well as an evaluation of body composition. The patients were then studied on two occasions in random order when they exercised for 45 min at their LT. On one occasion, GH replacement had been discontinued from the evening before, whereas on the other occasion they received their evening GH in addition to an intravenous infusion of GH (0.4 IU) during exercise the following day. The healthy subjects exercised at their LT on one occasion without GH. RESULTS: The patients were significantly more obese and had lower VO(2) max (corrected for body weight) and LT as compared with the control subjects. Exercise induced a peak in serum GH concentrations after 45 min in the control group (11.43+/-3.61 microg/l). Infusion of GH in the patients resulted in a peak level after 45 min, whereas no increase was detected when exercising without GH (9.77+/-2.40 (GH) vs 0.11+/-0.07 microg/l (no GH)). Plasma ghrelin levels did not change significantly with time in either study, and no correlations were detected between ghrelin levels and parameters such as GH and IGF-I levels, age or body composition. Plasma ghrelin levels were significantly lower during the study period with GH as compared with the study with no GH. CONCLUSIONS: Submaximal aerobic exercise of an intensity sufficient to stimulate GH release was not associated with significant alterations in plasma ghrelin concentrations, which indicated that systemic ghrelin is not involved in the exercise-induced stimulation of GH secretion. The observation that ghrelin levels were lower during GH replacement suggests that GH may feedback-inhibit systemic ghrelin release.

Adult↗
PubMed2002

Somatropin and glucose homeostasis: considerations for patient management.

More than 60 years ago it was shown, in dogs, that anterior pituitary extracts may cause glucose intolerance and that hypophysectomy was associated with increased insulin sensitivity. Accordingly, active acromegaly is characterized by insulin resistance at the hepatic and muscular level, whereas children with growth hormone (GH) deficiency are insulin hypersensitive and prone to developing fasting hypoglycemia. Somewhat unexpectedly, hypopituitary adults with untreated GH deficiency tend to be insulin resistant, which may be aggravated by somatropin (GH) therapy. The explanation for this apparent paradox has not been fully established. It is, however, likely that high circulating levels of free fatty acids (FFA) are responsible for insulin resistance, both before and after somatropin therapy. In the untreated state, patients have abdominal obesity, which increases circulating FFA levels. Since GH has potent lipolytic effects, somatropin therapy will further increase FFA levels. Theoretically, this GH replacement effect will eventually be compensated for by favorable alterations in body composition, including a reduction of fat mass. Subcutaneous somatropin therapy, however, will cause some degree of hypersomatropinemia in the prandial phase, which will inevitably antagonize the physiologic effects of insulin. At present, the best way to circumvent this inherent problem is to employ evening injections of somatropin and to ensure that the dosage is not too high. In the latter regard, it is important to realize that dosage requirements are lower in adults compared with children, and that the dosage will probably need to be reduced with age in the individual patient.

Acromegaly↗