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N Møller

Publications and source records attributed to N Møller.

At least 73 records · Page 4Linked to original sources
PubMed1995

Fuel metabolism in growth hormone-deficient adults.

Apart from being a stimulator of longitudinal growth, growth hormone (GH) regulates fuel metabolism in children and adults. A halfmark is mobilization of lipids, which involves an inhibition of lipoprotein lipase activity in adipose tissue and activation of the hormone sensitive lipase. Suppression of basal glucose oxidation and resistance to insulin are other important effects. This may cause concern during GH substitution in GH-deficient adults, some of whom may present with insulin resistance due to concomitant abdominal obesity. However, there are data to suggest that the GH-induced reduction in fat mass and increase in lean body mass may offset the insulin antagonistic actions of the hormone. The nitrogen-retaining effects of GH seem to involve a direct stimulation of protein synthesis in addition to secondary effects such as generation of insulin-like growth factor-I (IGF-I), hyperinsulinemia, and promotion of lipolysis. Thus, during periods of substrate affluence, GH acts in concert with insulin and IGF-I to promote protein anabolism. Postabsorptively, GH is primarily lipolytic and thereby indirectly protein-sparing. This effect becomes further accentuated with more prolonged fasting. In that sense, GH is unique by its preservation of protein during both feast and famine. These fuel metabolic effects add merit to the principle of GH substitution in hypopituitary adults.

Adult↗
PubMed1995

Forearm substrate exchange during hyperinsulinaemic hypoglycaemia in normal man.

To assess muscle substrate exchange during hypoglycaemia, 8 healthy young male subjects were studied twice during 2 h of hyperinsulinaemic euglycaemia followed by 4 h of (1) hypoglycaemia (plasma glucose < 2.8 mmol l-1), and (2) euglycaemia. Insulin was infused at a rate of 1.5 mU kg-1 min-1 throughout. When compared to euglycaemia, hypoglycaemia was associated with: (1) increment in circulating glucagon (65 +/- 8 vs 23 +/- 4 ng l-1, p < 0.05), growth hormone (19.9 +/- 3.6 vs 2.6 +/- 1.3 micrograms l-1, p < 0.05), adrenaline (410 +/- 88 vs 126 +/- 32 ng l-1, p < 0.05) and increased suppression of C-peptide (0.5 +/- 0.1 vs 1.0 +/- 0.1 micrograms l-1, p < 0.05) along with a modest lowering of insulin (103 +/- 10 vs 130 +/- 13 mU l-1, p < 0.05); (b) decrease in plasma glucose level (3.0 +/- 0.07 vs 5.0 +/- 0.12 mmol l-1, p < 0.05), forearm glucose uptake (0.21 +/- 0.09 vs 1.21 +/- 0.21 mmol l-1, p < 0.05) and requirement for exogenous glucose (5.6 +/- 1.1 vs 13.2 +/- 0.9 mg kg-1 min-1 p < 0.005) together with an impaired suppression of isotopically determined endogenous glucose production (0.34 +/- 0.5 vs -2.3 +/- 0.3 mg kg-1 min-1, p < 0.05); (3) exaggerated increase in blood lactate (1680 +/- 171 vs 1315 +/- 108 mumol l-1, p < 0.05) and a decrease in alanine (215 +/- 18 vs 262 +/- 19 mumol l-1, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Somatostatin enhances insulin-stimulated glucose uptake in the perfused human forearm.

Somatostatin is widely used in experimental metabolic studies to control hormone actions. It has also been suggested that, in addition to its well known suppressive effects, somatostatin per se may increase insulin sensitivity. In order to examine this suggestion, we gave six healthy male volunteers (age 33 +/- 1 yr, mean +/- SEM; body mass index, 24.1 +/- 0.6 kg/m2) either a local intraarterial (brachial artery) or a systemic venous infusion of 25 micrograms/h somatostatin twice. The study consisted of a 1-h basal period and a 2-h systemic hyperinsulinemic (0.4 mU/kg.min) euglycemic clamp. Compared with the systemic control infusion, local forearm perfusion with somatostatin caused a 55% increase in insulin-stimulated forearm glucose uptake (0.74 +/- 0.18 vs. 0.47 +/- 0.19 mmol/L, P < 0.05). Intraarterial somatostatin perfusion did not alter basal forearm glucose uptake (0.14 +/- 0.07 vs. 0.17 +/- 0.12 mmol/L), the amount of glucose administered during the clamp (M-value, 3.2 +/- 0.5 vs. 3.0 +/- 0.6 mg/kg.min), or the levels of insulin, C-peptide, glucagon, or GH. Intermediary metabolite exchange across the forearm, total forearm blood flow, and oxygen saturations also remained stable. Glucose concentrations were slightly higher (0.06 +/- 0.01 mmol/L) in arterial than in arterialized blood, whereas lactate concentrations were comparatively decreased (108 +/- 51 mumol/L) in arterial blood. Our data suggest that somatostatin increases insulin-stimulated muscle utilization of glucose through local mechanisms. Although the nature of this increase remains to be established, it should be taken into consideration in metabolic studies using somatostatin.

3-Hydroxybutyric Acid↗
PubMed1994

Effects of glipizide on glucose metabolism and muscle content of the insulin-regulatable glucose transporter (GLUT 4) and glycogen synthase activity during hyperglycaemia in type 2 diabetic patients.

To examine whether sulphonylureas influence hyperglycaemia-induced glucose disposal and suppression of hepatic glucose production (HGP) in type 2 diabetes mellitus, a 150-min hyperglycaemic (plasma glucose 14 mmol/l) clamp with concomitant somatostatin infusion was used in eight type 2 diabetic patients before and after 6 weeks of glipizide (GZ) therapy. During the clamp a small replacement dose of insulin was given (0.15 mU/kg per min). Isotopically determined glucose-induced glucose uptake was similar before and after GZ administration which led to improved glycaemic control (basal plasma glucose 12.2 +/- 1.3 vs 8.9 +/- 0.7 mmol/l; P < 0.01). Glucose-induced suppression of HGP was, however, more pronounced during GZ treatment (0.96 +/- 0.14 vs 1.44 +/- 0.20 mg/kg per min; P < 0.02). Following GZ treatment hyperglycaemia failed to stimulate glycogen synthase activity. Moreover, GZ resulted in a significant increase in the immunoreactive abundance of the insulin-regulatable glucose transport protein (GLUT 4) (P < 0.02). In conclusion, these results suggest that GZ therapy in type 2 diabetic patients enhances hepatic sensitivity to hyperglycaemia, while glucose-induced glucose uptake remains unaffected. In addition, GZ tends to normalize the activity of glycogen synthase and increases the content of GLUT 4 protein in skeletal muscle.

Adult↗
PubMed1994

Insulin-like growth factors (IGF)-I and -II and IGF binding protein-1, -2, and -3 in patients with acromegaly before and after adenomectomy.

The interrelationship between insulin-like growth factors (IGFs) and their major binding proteins (IGFBPs) as a function of disease activity in acromegaly has not previously been prospectively evaluated. We studied basal and insulin-stimulated serum levels of IGF-I and -II and IGFBP-1, -2, and -3 in six acromegalic patients before and 2 months after successful adenomectomy compared with a group of sex- and age-matched healthy, untreated subjects. All were studied postabsorptively (11 AM) and at the end of a 2-hour euglycemic glucose clamp (0.4 mU insulin/kg x min). Serum IGF-I levels (mean +/- SE) were elevated in acromegaly but were normalized following therapy (basal state IGF-I [micrograms/L], 857 +/- 119 [active] v 255 +/- 65 [postoperative] v 190 +/- 20 [control]). Serum IGF-II levels did not change following therapy and were similar to those of the control group. IGF levels did not change during the clamp. Serum IGFBP-3 levels were elevated in active acromegaly, but were normalized after therapy (basal state IGFBP-3 [micrograms/L] 6,983 +/- 612 [active] v 3,939 +/- 504 [postop] v 3,358 +/- 125 [control]). The molar ratio of (IGF-I+IGF-II): IGFBP-3 was similar in all studies. Serum IGFBP-1 interacted significantly with time in all studies, exhibiting a gradual decrease in the basal state and ensued by further suppression during the clamp. Insulin and IGFBP-1 correlated inversely in the pooled data and in the acromegalic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1994

Augmented effect of short-term pulsatile versus continuous insulin delivery on lipid metabolism but similar effect on whole-body glucose metabolism in obese subjects.

The present study was designed to examine the effect of pulsatile versus continuous insulin delivery on glucose and lipid metabolism in insulin-resistant subjects. Six obese women (body mass index, 40.0 +/- 2.8 kg/m2) underwent a euglycemic glucose clamp (plasma glucose, 90 mg/dL) twice. In random order, insulin was infused intravenously for 375 minutes either at a constant rate (0.4 mU/kg/min) or in a pulsatile manner (2.4 mU/kg/min for 2 minutes followed by an off interval of 10 minutes). Endogenous insulin release was suppressed by infusion of somatostatin (250 micrograms/h). Mean circulating insulin concentrations were similar during the two protocols (pulsatile v continuous infusion, 60 +/- 10 v 56 +/- 9 mU/L), but pulsatile infusion was accompanied by oscillations with an amplitude of 120 mU/L. After 6 hours of pulsatile versus continuous insulin, isotopically determined total glucose disposal (3-3H-glucose) and hepatic glucose production (HGP) were comparable (pulsatile v continuous, 2.80 +/- 0.56 v 2.82 +/- 0.51 and 0.37 +/- 0.14 v 0.32 +/- 0.17 mg/kg/min). However, the rate of glucose oxidation (indirect calorimetry) was augmented (P < .05), whereas lipid oxidation tended to be diminished (.10 > P > .05) following pulsatile infusion. In addition, blood glycerol was more suppressed with pulsatile (31 +/- 9 nmol/L) than with continuous infusion (36 +/- 10 nmol/L, P < .05), whereas blood lactate, alanine, and 3-hydroxybutyrate were similar in the two infusion protocols.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1994

Fuel metabolism, energy expenditure, and thyroid function in growth hormone-treated obese women: a double-blind placebo-controlled study.

Growth hormone (GH) promotes protein anabolism and lipolysis. Its effects on glucose metabolism include suppression of glucose oxidation and may be associated with insulin resistance. In addition, GH stimulates energy expenditure (EE) and peripheral thyroid hormone metabolism. GH secretion is reduced in obese patients, but whether this is of pathophysiological significance is incompletely understood. In a double-blind placebo-controlled crossover design, we studied the effects of GH administration (0.03 mg.kg ideal body weight [IBW]-1.d-1) on fuel metabolism, EE, and thyroid function in 10 obese women (age, 30.4 +/- 2.4 years; body mass index [BMI], 37.0 +/- 2.8 kg/m2, mean +/- SE) with a normal prestudy oral glucose tolerance test (OGTT). Each treatment period (GH or placebo) lasted 5 weeks, separated by a 5-week washout period. At the end of each treatment period, subjects were studied in the basal state (8:00 AM) and during a euglycemic glucose clamp including indirect calorimetry and isotopic measurement of glucose turnover. Lean body mass (LBM) was assessed at the end of each period by dual-energy x-ray absorptiometry. In the basal state, GH induced a significant increase in circulating levels of free fatty acids (FFA), glucose, insulin, and C-peptide. This was associated with a significant increase in resting EE (kcal/24 h, 1,934 +/- 92 placebo v 2,323 +/- 134 GH, P < .001), a decrease in the respiratory exchange ratio (RER), and increased rates of lipid oxidation (mg.kg LBM-1.min-1, 1.55 +/- 0.09 placebo v 2.20 +/- 0.13 GH, P < .01). GH increased the rate of total basal glucose turnover, whereas oxidative glucose disposal was significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effect of needle biopsy from the vastus lateralis muscle on insulin-stimulated glucose metabolism in humans.

To examine the cellular mechanisms behind conditions characterized by insulin resistance, the clamp technique is often combined with muscle biopsies. To test whether the trauma of a needle biopsy from the vastus lateralis muscle per se may influence insulin-stimulated glucose uptake, eight healthy subjects underwent two randomly sequenced hyperinsulinemic (insulin infusion rate: 0.6 mU.kg-1.min-1 for 150 min) euglycemic clamps with an interval of 4-6 wk. In one study (study B) a muscle biopsy (approximately 250 mg, i.e., larger than normal standard) was taken in the basal state just before the clamp procedure, whereas the other was a control study (study C). Insulin-stimulated glucose uptake was significantly reduced in study B (5.36 +/- 0.96 mg.kg-1.min-1) compared with study C (6.06 +/- 0.68 mg.kg-1.min-1; P < 0.05). Nonoxidative glucose disposal (indirect calorimetry) was decreased (2.81 +/- 1.08 vs. 3.64 +/- 1.34 mg.kg-1.min-1; P < 0.05), whereas glucose oxidation was unaltered. Likewise, endogenous glucose output ([3-3H]glucose) was identically suppressed during hyperinsulinemia. Circulating levels of epinephrine, glucagon, and growth hormone did not differ significantly in studies B and C. In contrast, plasma norepinephrine, serum cortisol, and free fatty acid rose after biopsy (P < 0.05). In conclusion, performance of a muscle biopsy may diminish insulin sensitivity by affecting nonoxidative glucose metabolism. This should be considered when assessing whole body insulin sensitivity after a percutaneous needle muscle biopsy.

Adult↗
PubMed1994

Effects of growth hormone (GH) administration on functional hepatic nitrogen clearance: studies in normal subjects and GH-deficient patients.

A decline in serum urea levels and urinary urea excretion is usually seen after GH administration in humans, indicating overall protein anabolism. Whether this reflects the diminished supply of alpha-amino acids for urea synthesis or a substrate-independent hepatic mechanism is unknown. To pursue this we measured the urea nitrogen synthesis rate (UNSR) and blood alanine levels before, during, and after a 4-h constant iv infusion of alanine (2 mmol/kg BW.h). UNSR was estimated hourly as urinary excretion corrected for gut hydrolysis and accumulation in total body water. The slope of the linear relationship between UNSR and circulating alanine levels represents the hepatic components of conversion of amino nitrogen and is denoted the functional hepatic nitrogen clearance (FHNC). Eight male volunteers were randomly investigated on three occasions: 1) after 12-h iv saline infusion, 2) after 12-h iv GH infusion (1 IU/h), and 3) after 2-day sc GH treatment (8 IU/day), followed by 12-h iv infusion of GH (1 IU/h). The UNSR (millimoles per h) during alanine infusion was significantly lower when the subjects were receiving GH therapy [maximum +/- SE, 133.0 +/- 6.9 (saline) vs. 96.7 +/- 11.1 (12-h GH; P < 0.01) vs. 106.5 +/- 7.5 (2-day GH; P < 0.05)]. FHNC (liters per h) was similar in all three studies [30.3 +/- 1.2 (saline) vs. 26.6 +/- 3.4 (12-h GH) vs. 27.0 +/- 2.6 (2-day GH)]. Six GH-deficient adult patients were randomly studied twice: 1) on regular daily (at 2000 h) sc GH therapy (3 IU/m2.day), and 2) after discontinuation of GH for 2 days. The UNSR during alanine infusion was likewise significantly lower when the patients were receiving GH therapy [147.7 +/- 11.7 mmol/h (no GH) vs. 123.9 +/- 9.1 mmol/h; P < 0.01]. FHNC (liters per h) values were similar in the two studies [29.2 +/- 3.8 (GH) vs. 27.5 +/- 4.5 (no GH)]. Our data confirm the anabolic action of GH and show that short term GH deprivation is associated with catabolism in terms of increased UNSR. The finding of unaltered FHNC suggests a GH-induced extrahepatic regulation of amino nitrogen conversion, rather than a substrate-independent hepatic mechanism.

Adult↗
PubMed1993

Insulin resistance in microvascular angina (syndrome X)

Patients with microvascular angina (syndrome X) may be insulin resistant. We designed a study to establish whether this is the case. 11 patients with microvascular angina were compared with 9 matched subjects with noncardiac chest pain. Patients and controls were evaluated by coronary sinus catheterisation, and by isotopic measurement of glucose turnover, indirect calorimetry, and forearm technique during a 3 h baseline period after overnight fast and during a 2 h hyperinsulinaemic euglycaemic clamp. Pace-induced increase in coronary sinus blood flow was less in patients than in controls, whereas forearm blood flow did not differ between groups. Baseline measures of glucose metabolism were normal. During the clamp, glucose production and lipolysis were equally suppressed in both groups. Mean (SE) total insulin-induced glucose uptake was significantly impaired in patients compared with controls (3.9 [0.7] vs 6.4 [0.7] mg/kg per min; p < 0.01), and insulin-stimulated glucose uptake in the forearm was significantly reduced in patients (0.88 [0.10] vs 1.6 [0.30] mmol/L; p < 0.001). Reduced oxidative and nonoxidative metabolism accounted for the defect in overall glucose uptake in patients. No correlation between changes in coronary sinus blood flow and total body glucose uptake was seen. We found that microvascular angina was associated with substantial insulin resistance. Whether this relation is causal or coincidental is as yet unsettled.

Alanine↗
PubMed1993

Renal function and insulin sensitivity during simvastatin treatment in type 2 (non-insulin-dependent) diabetic patients with microalbuminuria.

The effect of simvastatin (10-20 mg/day) on kidney function, urinary albumin excretion rate and insulin sensitivity was evaluated in 18 Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria and moderate hypercholesterolaemia (total cholesterol > or = 5.5 mmol.l-1). In a double-blind, randomized and placebo-controlled design treatment with simvastatin (n = 8) for 36 weeks significantly reduced total cholesterol (6.7 +/- 0.3 vs 5.1 mmol.l-1 (p < 0.01)), LDL-cholesterol (4.4 +/- 0.3 vs 2.9 +/- 0.2 mmol.l-1 (p < 0.01)) and apolipoprotein B (1.05 +/- 0.04 vs 0.77 +/- 0.02 mmol.l-1 (p < 0.01)) levels as compared to placebo (n = 10). Both glomerular filtration rate (mean +/- SEM) (simvastatin: 96.6 +/- 8.0 vs 96.0 +/- 5.7 ml.min-1 x 1.73 m-2, placebo: 97.1 +/- 6.7 vs 88.8 +/- 6.0 ml.min-1 x 1.73 m-2)(NS) and urinary albumin excretion rate (geometric mean x/divided by antilog SEM) (simvastatin: 18.4 x/divided by 1.3 vs 16.2 x/divided by 1.2 microgram.min-1, placebo 33.1 x/divided by 1.3 vs 42.7 x/divided by 1.3 micrograms.min-1)(NS) were unchanged during the study. A euglycaemic hyperinsulinaemic clamp was performed at baseline and after 18 weeks in seven simvastatin- and nine placebo-treated patients. Isotopically determined basal and insulin-stimulated glucose disposal was similarly reduced before and during therapy in both the simvastatin (2.0 +/- 0.1 vs 1.9 +/- 0.1 (NS) and 3.1 +/- 0.6 vs 3.1 +/- 0.7 mg.kg-1 x min-1 (NS)) and the placebo group (1.9 +/- 0.1 vs 1.8 +/- 0.1 (NS) and 4.1 +/- 0.6 vs 3.8 +/- 0.2 mg.kg-1 x min-1 (NS)).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Lack of impact of pharmacological growth hormone administration on circulating levels of reproductive hormones during the menstrual cycle in normal women.

OBJECTIVE: To evaluate the effects of pharmacological growth hormone (GH) administration on the secretion of pituitary and gonadal hormones during the menstrual cycle in normal women. DESIGN: Randomized, double-blind, placebo-controlled crossover design. PATIENTS, PARTICIPANTS: Six normally menstruating, healthy women, 22 to 24 years of age and with a normal body mass index. INTERVENTIONS: Each participant was treated with placebo and growth hormone (12 IU/d) during two different 14-day periods, separated by a 6-week washout period. MAIN OUTCOME MEASURES: Serum insulin-like growth factor I (IGF-I), estradiol, progesterone, follicle-stimulating hormone, and luteinizing hormone. RESULTS: Administration of GH for 14 days resulted in a significant increase in serum IGF-I, whereas no changes occurred in gonadotropin or sex steroid response. CONCLUSIONS: Growth hormone treatment during the first 14 days of menstrual cycle in normal women does not affect gonadotropin or sex steroid patterns.

Adult↗
PubMed1993

Evidence for increased sensitivity of fuel mobilization to growth hormone during short-term fasting in humans.

Since growth hormone (GH) secretion is increased with fasting, the study was designed to assess the effects of short-term fasting on both basal and GH stimulated substrate metabolism. Seven normal healthy subjects were studied following a 12 h and a 36 h fast ("fasting"), for 2 h in the basal state and for a further 4 1/2 h after an i.v. bolus injection of 140 micrograms GH. As expected fasting induced decrements in circulating concentrations of insulin and C-peptide (p < 0.05) and increments in glucagon concentrations (p < 0.05), together with a slight increase in serum GH concentrations (p > 0.05). Furthermore plasma glucose values, isotopically determined turnover rate for glucose and forearm uptake of glucose were all substantially reduced during fasting (p < 0.05). By contrast circulating levels of all measured lipid intermediates (free fatty acids [FFA], 3-hydroxybutyrate [3-OHB] and glycerol) and the forearm uptake of 3-OHB were clearly elevated during the fast (p < 0.05). Serum GH rose to a peak of 17.0 +/- 2.7 within 10 min of injection in both situations. Blood concentrations of hormones and parameters of glucose metabolism remained unaffected. After administration of GH circulating levels of lipid intermediates increased markedly in both situations, the increase being most pronounced in the fasting state (p < 0.05). During fasting peak levels of 1775 +/- 150 mumol/l and 1780 +/- 360 mumol/l of FFA and 3-OHB were observed compared to postabsorptive peaks of 980 +/- 100 and 230 +/- 90 mumol/l respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of growth hormone administration on circulating levels of luteinizing hormone, follicle stimulating hormone and testosterone in normal healthy men.

A new area of growth hormone (GH) therapy in adults is the treatment of infertility. The aim of this study was to evaluate the effects of pharmacological GH administration on the secretion of pituitary and gonadal hormones in normal men. Eight healthy men, 23-32 years of age (mean 28.1 years), with a normal body mass index were studied in a double-blind, placebo-controlled crossover design. All participants had a normal semen analysis before entering the study. Each participant was treated with placebo and GH (12/IU/day, Norditropin; Novo Nordisk, Denmark) during two different 14-day periods, separated by a 6 week washout period. Administration of GH for 14 days resulted in a significant increase in serum insulin-like growth factor I (IGF-I; P < 0.01) but no changes occurred in IGF-I values during placebo treatment. The concentrations of follicle stimulating hormone and luteinizing hormone displayed no change during the two periods and did not differ between the GH treatment period and the placebo period. The concentration of testosterone was unchanged during the placebo/GH periods and there was no difference between the GH treatment period and the placebo period. We conclude that GH treatment for 14 days in normal healthy men does not affect gonadotrophin or testosterone patterns.

Adult↗
PubMed1993

Impact of 2 weeks high dose growth hormone treatment on basal and insulin stimulated substrate metabolism in humans.

OBJECTIVE: Short-term, high dose growth hormone (GH) treatment has been advocated in many catabolic disease states. It is likely that some of the anabolic effects of GH are mediated through activation of lipolysis, but the metabolic impact of therapeutically relevant GH exposure is not known in detail. The present study was accordingly designed to assess the effects of such GH exposure on basal and insulin stimulated intermediary metabolism. DESIGN, PATIENTS AND MEASUREMENTS: Six healthy young females were examined following daily injections of GH (12 IU/day) or saline for 2 weeks in a placebo controlled design. Each study consisted of a 3 hour basal period and a 2 hour hyperinsulinaemic euglycaemic clamp. RESULTS: GH treatment caused (1) increased levels of IGF-I (382 +/- 46 vs 294 +/- 22 micrograms/l, P < 0.05) and (2) increased basal values of free fatty acids (714 +/- 40 (GH) vs 634 +/- 64 (placebo) mumol/l, P < 0.05), 3-hydroxybutyrate (118.3 +/- 42.8 (GH) vs 57.7 +/- 21.6 (placebo) mumol/l, P < 0.05), glycerol (54.3 +/- 8.2 (GH) vs 41.4 +/- 8.4 (placebo) mumol/l, P < 0.05) and forearm uptake of 3-hydroxybutyrate, together with increments of plasma glucose (5.28 +/- 0.11 (GH) vs 4.87 +/- 0.16 (placebo) mmol/l, P < 0.05). Basal forearm uptake of glucose, isotopically determined glucose turnover and serum levels of GH, insulin and C-peptide were unaltered. During the clamp GH treatment was associated with (1) a 40% decrease in the administered amount of glucose (M-value) (P < 0.05) and (2) a 70% decrease in forearm glucose uptake (P < 0.05). Indirect calorimetry revealed a 15% increase in resting energy expenditure (P < 0.05) and a decreased basal respiratory exchange ratio (0.75 (GH) vs 0.80 (placebo), P < 0.05), presumably reflecting increased lipid oxidation. CONCLUSIONS: Administration of GH in a therapeutic dose for 2 weeks, despite apparently normal daytime levels of major metabolic hormones, induces significant increases in circulating lipid fuel substrates, increased energy expenditure and lipid oxidation, together with insulin resistance. Such effects should be considered when applying GH treatment schedules clinically.

Adult↗
PubMed1993

Lipoprotein lipase activity in muscle tissue influenced by fatness, fat distribution and insulin in obese females.

Obesity is associated with dyslipidaemia and increased morbidity and mortality from premature atherosclerosis and diabetes mellitus. Particularly, hypertriglyceridaemia is a characteristic finding in patients with obesity. In addition, the elevated levels of triglycerides may be an important risk factor for development of the obesity-related complications. Lipoprotein lipase activity in skeletal muscle tissue (mLPL) has previously been found to be an important factor regulating the concentration of serum triglycerides. To describe the relationship between mLPL, triglycerides and fatness/fat distribution in more detail we have investigated these parameters under basal conditions and during insulin stimulation in 20 obese females. During hyperinsulinaemia (204 microU ml-1) for 4 h the mLPL activity decreased from 528 +/- 52 nmol FFA g-1 to 412 +/- 44 (P < 0.001). Basal mLPL was negatively correlated with serum triglycerides (r = -0.48, P < 0.05) and positively correlated with HDL-cholesterol (r = 0.58, P < 0.01). Employing multiple variance analysis it was found that both BMI and WHR were negatively correlated to mLPL, however, the impaired lipid profile (high triglyceride, low HDL-cholesterol, high FFA) could only be related to BMI and not to WHR in these obese females. However, reduced insulin-action (insulin resistance) was closely related to abdominal fatness determined by WHR both in relation to the insulin-effect on mLPL as well as for the insulin-effect on whole-body glucose metabolism (clamp-study).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1993

Insulin-like growth factors (IGF) I and II and IGF binding proteins 1, 2 and 3 during low-dose growth hormone (GH) infusion and sequential euglycemic and hypoglycemic glucose clamps: studies in GH-deficient patients.

To evaluate the short-term effects of growth hormone (GH), insulin and different levels of glycemia on insulin-like growth factors (IGF) I and II and IGF binding proteins (IGFBP) 1, 2 and 3, we studied six GH-deficient adolescents during a night and the following day in the postabsorptive (basal) state followed by sequential euglycemic (5 mmol/l) and hypoglycemic (3 mmol/l) glucose clamps concomitant with an intravenous infusion (starting at 24.00 h) of GH (35 micrograms/h) or saline. Current GH therapy was withdrawn 24 h prior to each study. Nocturnal levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 remained stable during both studies. Nocturnal serum IGFBP-1 increased and correlated inversely with insulin in both studies. Regression analysis revealed a significant inverse correlation between mean nocturnal IGFBP-2 and IGFBP-3 levels. During the daytime, serum IGF-I declined slowly during saline infusion, whereas serum IGF-II remained stable in both studies. Serum IGFBP-1 displayed a gradual significant decline during the basal state and the euglycemic and hypoglycemic clamps seemed to be unaffected by GH levels. By contrast, serum IGFBP-2 remained stable during the same period in both the GH and the saline study. Serum IGFBP-3 declined insignificantly during the daytime in the saline study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗