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Biomedical subjects

Helene Nørrelund

Publications and source records attributed to Helene Nørrelund.

At least 19 recordsLinked to original sources
PubMed2006

Adaptation of nonrevascularized human hibernating and chronically stunned myocardium to long-term chronic myocardial ischemia.

It is unknown whether human chronically ischemic dysfunctional myocardium degenerates over time or adapts to chronic ischemia. We studied whether perfusion, metabolism, and contractile function and reserve can be preserved in nonrevascularized human chronically stunned and hibernating myocardium. We studied 16 event-free, medically treated patients with ejection fractions of 31 +/- 2% and chronically stunned or hibernating myocardium in 56 +/- 5% of the left ventricle on technetium-99m sestamibi single-photon emission computed tomography/fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography. Patients underwent repeat single-photon emission computed tomography, positron emission tomography, and tissue Doppler echocardiography at rest and during stress at follow-up after 25 +/- 4 months, and we investigated whether measurements of myocardial viability remained stable over time. Patients were stable with respect to New York Heart Association class and global left ventricular function (30 +/- 2%, p = 0.81). Wall motion score was unaltered in hibernating myocardium and chronically stunned regions, and a contractile reserve by tissue Doppler stress echocardiography was preserved. Overall, 74% of hibernating myocardium and chronically stunned regions retained their initial perfusion/metabolism pattern at follow-up. In hibernating myocardium, initial and follow-up sestamibi uptakes (53 +/- 1% and 53 +/- 2%, p = 0.85) and FDG uptakes (76 +/- 1% and 74 +/- 1%, p = 0.21) did not differ. In chronically stunned regions, sestamibi uptake displayed a minor decrease at follow-up (70 +/- 1% vs 67 +/- 1%, p <0.01) and FDG uptake remained constant (68 +/- 2% and 67 +/- 1%, p = 0.21). In conclusion, myocardial perfusion, FDG uptake, and contractile function in nonrevascularized chronically stunned and hibernating myocardium adapt to chronic ischemia in patients who are free of events. In chronically stunned regions, adaptation may be less complete than in hibernating myocardium.

Adaptation, Physiological↗
PubMed2005

Influence of insulin and free fatty acids on contractile function in patients with chronically stunned and hibernating myocardium.

It is unknown whether short-term modulation of substrate supply affects cardiac performance in heart failure patients with chronic ischemic myocardium. The aim of this study was to determine whether modulation of myocardial substrate metabolism with insulin and free fatty acids (FFAs) affects contractile function of chronically stunned (CST) and hibernating (HIB) myocardium at rest and after maximal exercise. We studied eight nondiabetic patients with ejection fraction (EF) 30 +/- 4% (SE) and CST/HIB in 49 +/- 6% of the left ventricle: 36 +/- 6% CST and 13 +/- 2% HIB as determined by 99m Technetium-Sestamibi single photon emission computed tomography (SPECT) and [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Each patient was subjected to a 3-h infusion of 1) saline, 2) insulin-glucose (i.e., euglycemic insulin clamp; high insulin, suppressed FFA), and 3) somatostatin-heparin (suppressed insulin, high FFA). Echocardiographic endpoints were global EF and regional contractile function [maximum velocity (Vmax) and strain rate (epsilon max)] as determined by tissue Doppler imaging at steady state and after maximal exercise. EF was similar at baseline and steady state and increased after exercise to 36 +/- 5% (P < 0.05). Baseline regional Vmax and epsilon max were highest in control, intermediate in CST and HIB, and lowest in infarct regions (P < 0.05). Steady-state EF, Vmax, and epsilon max were not affected by metabolic modulation in any region. After maximal exercise, contractile function increased in control, CST, and HIB (P < 0.05), but not in infarct, regions. Exercise-induced contractile increments were unaffected by metabolic modulation. Metabolic modulation does not influence contractile function in CST and HIB regions. Chronic ischemic myocardium has preserved ability to adapt to extreme, short-term changes in substrate supply at rest and after maximal exercise.

Aged↗
PubMed2005

Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown.

Thyroid hormones have significant metabolic effects, and muscle wasting and weakness are prominent clinical features of chronic hyperthyroidism. To assess the underlying mechanisms, we examined seven hyperthyroid women with Graves' disease before (Ht) and after (Eut) medical treatment and seven control subjects (Ctr). All subjects underwent a 3-h study in the postabsorptive state. After regional catheterization, protein dynamics of the whole body and of the forearm muscles were measured by amino acid tracer dilution technique using [15N]phenylalanine and [2H4]tyrosine. Before treatment, triiodothyronine was elevated (6.6 nmol/l) and whole body protein breakdown was increased 40%. The net forearm release of phenylalanine was increased in hyperthyroidism (microg.100 ml(-1).min(-1)): -7.0 +/- 1.2 Ht vs. -3.8 +/- 0.8 Eut (P = 0.04), -4.2 +/- 0.3 Ctr (P = 0.048). Muscle protein breakdown, assessed by phenylalanine rate of appearance, was increased (microg.100 ml(-1).min(-1)): 15.5 +/- 2.0 Ht vs. 9.6 +/- 1.4 Eut (P = 0.03), 9.9 +/- 0.6 Ctr (P = 0.02). Muscle protein synthesis rate did not differ significantly. Muscle mass and muscle function were decreased 10-20% before treatment. All abnormalities were normalized after therapy. In conclusion, our results show that hyperthyroidism is associated with increased muscle amino acid release resulting from increased muscle protein breakdown. These abnormalities can explain the clinical manifestations of sarcopenia and myopathy.

Adult↗
PubMed2004

Growth hormone and glucose homeostasis.

Patients with active acromegaly are insulin-resistant and glucose-intolerant, whereas children with growth hormone (GH) deficiency (GHD) are insulin-sensitive and may develop fasting hypoglycaemia. Surprisingly, however, hypopituitary adults with unsubstituted GHD tend to be insulin-resistant, which may worsen during GH substitution. 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 favourable 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 hypoglycaemia and GH substitution may cause hyperglycaemia. Such untoward effects should be minimized by carefully monitoring the individual patient.

Acromegaly↗
PubMed2004

Modulation of basal glucose metabolism and insulin sensitivity by growth hormone and free fatty acids during short-term fasting.

BACKGROUND AND AIMS: The metabolic response to fasting involves an increase in circulating levels of growth hormone (GH) and free fatty acids, and resistance to insulin's actions on glucose metabolism. Stimulation of lipolysis and insulin resistance are well-described effects of GH. The present study was designed to test the degree to which the insulin antagonistic effects of GH on glucose metabolism are mediated through stimulation of lipolysis during fasting. METHODS: Seven normal subjects were examined on three occasions during a 40-h fast with infusion of somatostatin, insulin and glucagon for the final 18 h: (expt. i) with GH replacement, (expt. ii) with GH replacement and antilipolysis with acipimox, and (expt. iii) without GH and with antilipolysis. RESULTS: Basal glucose turnover was significantly reduced by addition of acipimox (rate of disappearance (Rd) glucose (mg/kg/min): 1.91+/-0.08 (expt. i), 1.69+/-0.05 (expt. ii), 1.61+/-0.08 (expt. iii); P<0.01), whereas insulin-stimulated glucose uptake was significantly increased (glucose infusion rate (M-value) (mg/kg/min): 1.66+/-0.22 (expt. i), 2.47+/-0.10 (expt. ii), 2.00+/-0.31 (expt. iii); P<0.05). Addition of GH during inhibition of lipolysis failed to affect basal and insulin-stimulated glucose metabolism significantly. CONCLUSION: Thus, the present data provide strong evidence that the insulin antagonistic effects of GH on fasting glucose metabolism are causally linked to concomitant stimulation of lipolysis.

Adult↗
PubMed2003

Effects of GH on urea, glucose and lipid metabolism, and insulin sensitivity during fasting in GH-deficient patients.

Fasting-related states of distress pose major health problems, and growth hormone (GH) plays a key role in this context. The present study was designed to assess the effects of GH on substrate metabolism and insulin sensitivity during short-term fasting. Six GH-deficient adults underwent 42.5 h of fasting on two occasions, with and without concomitant GH replacement. Palmitate and urea fluxes were measured with the steady-state isotope dilution technique after infusion of [9,10-3H]palmitate and [13C]urea. During fasting with GH replacement, palmitate concentrations and fluxes increased by 50% [palmitate: 378 +/- 42 (GH) vs. 244 +/- 12 micromol/l, P < 0.05; palmitate: 412 +/- 58 (GH) vs. 276 +/- 42 microM, P = 0.05], and urea turnover and excretion decreased by 30-35% [urea rate of appearance: 336 +/- 22 (GH) vs. 439 +/- 43 micromol. kg-1. h-1, P < 0.01; urea excretion: 445 +/- 43 (GH) vs. 602 +/- 74 mmol/24 h, P < 0.05]. Insulin sensitivity (determined by a euglycemic hyperinsulinemic clamp) was significantly decreased [M value: 1.26 +/- 0.06 (GH) vs. 2.07 +/- 0.22 mg. kg-1. min-1, P < 0.01] during fasting with GH replacement. In conclusion, continued GH replacement during fasting in GH-deficient adults decreases insulin sensitivity, increases lipid utilization, and conserves protein.

Adult↗
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

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

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

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

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↗