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Biomedical subjects

H Orskov

Publications and source records attributed to H Orskov.

At least 55 records · Page 3Linked to original sources
PubMed1998

Developmental changes in serum levels of free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 and -3, and the acid-labile subunit in rats.

We have recently described a competitive binding assay for rat insulin-like growth factor-binding protein-3 (IGFBP-3) based on the ability of IGFBP-3 to form a ternary complex with the acid-labile subunit (ALS) in the presence of IGF-I. Using this assay we studied groups of male (n = 6) and female rats (n = 6) at 20, 30, 40, 50, 60, 80, and 130 days of age. Nonfasting serum levels of IGFBP-3 were compared with those of total (extractable) IGF-I (tIGF-I) and ALS as well as IGFBP-3 determined by ligand blotting. Additionally, we studied the relationship between ultrafiltered free IGF-I (fIGF-I) and immunoassayable IGFBP-1. IGFBP-3 was dependent on age only (P < 0.0001), but tended to be higher in males than in females (P = 0.06); between 20-130 days levels increased from 6.5 +/- 1.7 to 73.6 +/- 7.2 nmol/liter in males and from 5.4 +/- 1.6 to 51.3 +/- 8.0 nmol/liter in females. IGFBP-3 correlated positively with tIGF-I (r = 0.90; P < 0.0001), ALS (r = 0.92; P < 0.0001), and IGFBP-3, as determined by ligand blotting (r = 0.88; P < 0.0001). The molar ratio of IGFBP-3 to tIGF-I increased from 0.23 +/- 0.04 to 0.76 +/- 0.04 (P < 0.0001) without any sex dependence. An age- and sex-dependent decrease in IGFBP-1 was observed (P < 0.0001), from 10.9 +/- 2.5 to 1.2 +/- 0.2 nmol/liter in females and from 8.9 +/- 0.7 to 0.2 +/- 0.04 nmol/liter in males. Free IGF-I (fIGF-I) increased with age (from 0.7 +/- 0.2 to 7.1 +/- 0.5 nmol/liter; P < 0.0001), and levels were inversely correlated with IGFBP-1 (r = -0.80; P < 0.0001). In young rats, IGFBP-1 circulated in a 10-fold molar excess over the level of fIGF-I, whereas in older rats, fIGF-I exceeded IGFBP-1 by an average of 9-fold in females and by up to almost 60-fold in males. We conclude that in rats 1) IGFBP-3 and fIGF-I are strongly age dependent; 2) IGFBP-3 correlates positively with ALS and tIGF-I; and 3) fIGF-I and IGFBP-1 are inversely correlated. This is in accordance with clinical findings. However, in humans the adult level of fIGF-I rarely exceeds 0.3 nmol/liter, and IGFBP-1 usually circulates in excess of fIGF-I. Thus, our results also imply species differences in the IGF systems of humans and rats.

Age Factors↗
PubMed1998

Growth hormone and mild exercise in combination markedly enhance cortical bone formation and strength in old rats.

The effects of a combination of mild exercise and GH injections on bone were studied in old female rats. Biosynthetic human GH, 2.7 mg/kg/day, was injected s.c. for 73 days. Exercised rats ran 8 m/min on a treadmill for 1 h/day. All rats (age 21 months old) were labeled with a tetracycline injection 56 days and a calcein injection 11 days before killing. The GH injections resulted in an 11-fold increase in femoral middiaphyseal bone formation rate and a 12% increase in cross-sectional area compared with the saline-injected group. The mild exercise doubled the mineralizing surface but did not influence the bone formation rate significantly. The combination of GH injections plus exercise, however, resulted in a further increase of 39% in bone formation rate, primarily at the anterolateral aspects, and an increase of 5% in cross-sectional area compared with the group injected with GH only. The femur ultimate breaking load was increased by 37% and the stiffness by 42% in the group injected with GH compared with the saline-injected group. Exercise alone did not influence the femur mechanical properties. The combination of GH injections plus exercise induced a 4% further increase in ultimate breaking load and 7% further increase in stiffness compared with the group injected with GH alone. The GH injections induced a 117% increase in serum insulin-like growth factor I. The GH-insulin-like growth factor I axis stimulates recruitment of osteoblast precursor cells, resulting in increased bone formation at the periosteal surface. GH injections and mild excercise in combination modulate and increase further the formation and strength of cortical bone in old female rats.

Aging↗
PubMed1998

No effect of growth hormone on serum insulin-like growth factor binding protein-3 proteolysis.

Increased proteolysis of insulin-like growth factor binding protein (IGFBP)-3 is seen in several pathophysiological conditions and may represent an important mechanism for the regulation of insulin-like growth factor bioavailability. It has previously been suggested that proteolysis of IGFBP-3 is dependent on the GH status. To investigate this, IGFBP-3 proteolysis was measured in three groups of subjects: 1) GH-deficient patients before and after GH replacement (n = 14); 2) healthy subjects before and after 14 days of GH administration (n = 7); and 3) acromegalic patients before and after treatment with a long-acting SRIH analogue (octreotide; n = 14). In vivo IGFBP-3 proteolysis was investigated by Western immunoblotting. No difference was detected in pretreatment samples, and GH treatment in GH-deficient subjects or octreotide treatment in acromegalic subjects had no impact on in vivo proteolysis. In contrast, GH administration to healthy subjects caused a 21% increase in in vivo proteolysis (P = 0.0008). In vitro IGFBP-3 proteolysis was investigated by incubation of serum with 125I-rhIGFBP-3, followed by SDS-PAGE. In pretreatment samples, the percentage of proteolyzed 125I-rhIGFBP-3 was 13 +/- 1% (acromegalic subjects), 11 +/- 1% (healthy subjects), and 9 +/- 1% (GH-deficient subjects) (P < 0.009, GH-deficient vs. acromegalic subjects). Treatment had no effect on in vitro proteolysis. We conclude that GH status has no major impact on IGFBP-3 protease activity in serum.

Acromegaly↗
PubMed1998

Differential changes in free and total insulin-like growth factor I after major, elective abdominal surgery: the possible role of insulin-like growth factor-binding protein-3 proteolysis.

Major surgery is accompanied by extensive proteolysis of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3). Proteolysis of IGFBP-3 is generally believed to increase IGF bioavailability due to a diminished affinity of the IGFBP-3 fragments for IGFs. We have investigated 18 patients undergoing elective ileo-anal J-pouch surgery. Patients were randomized to treatment with GH (12 IU/day; n = 9) or placebo (n = 9) from 2 days before to 7 days after operation. Free IGF-I and IGF-II were measured by ultrafiltration of serum, and IGFBP-3 proteolytic activity was determined by a [125I]recombinant human IGFBP-3 degradation assay. In the GH-treated group, total IGF-I increased preoperatively by 99%. Postoperatively, total IGF-I decreased by 48% (placebo) and 52% (GH). Immunoassayable IGFBP-3 decreased by 27% (placebo) and 26% (GH). In the placebo-treated group, free IGF-I was unchanged throughout the study. In the GH-treated group, free IGF-I increased by 277% preoperatively and remained elevated after operation. IGFBP-3 proteolytic activity increased by 63-73% after operation. The relative elevations of free IGF-I levels despite decreased total IGF-I levels could thus relate to augmented IGFBP-3 proteolysis.

Adult↗
PubMed1998

GH stimulation tests: evaluation of GH responses to heat test versus insulin-tolerance test.

OBJECTIVE: Heat exposure has been shown to stimulate GH release, but the specificity and the reproducibility have not been determined, and the test has not been compared with validated GH stimulation tests in adulthood. We therefore tested the specificity and the reproducibility of the heat exposure test in healthy subjects and compared the results with those obtained with the insulin-tolerance test (ITT). DESIGN: Ten healthy non-obese men, aged 31.3+/-4.80 years, underwent four GH stimulation tests in random order: two ITTs and two heat exposure tests. In the heat test, subjects were placed in a hot bath with water temperature at 40.3+/-0.11 degrees C for 45 min, resulting in an identical (P = 0.477) significant increase in tympanic temperature of 1.26+/-0.05 and 1.41+/-0.07 degrees C in the two tests. RESULTS: Peak GH response to the heat exposure test was less than the peak GH response to ITT (5.25+/-1.72 vs 15.5+/-3.17 microg/l, P = 0.006). Furthermore the specificity (arbitrary cut-off level = 3 microg/l) of the heat test was lower than of the ITT (8/17 vs 18/20, P = 0.006). The coefficient of variation did not differ between the two tests (heat test 0.31, ITT 0.36, P = 0.77). Peak GH values in the individual tests were highly correlated (heat, r = 0.908, P = 0.002; ITT, r = 0.815, P = 0.004). Reproducible increments in the circulating levels of stress hormones were observed during ITT. but these hormones remained largely unchanged during heat exposure. CONCLUSIONS: The heat exposure test is not a reliable GH stimulation test compared with the ITT in adults. This study documents that the ITT has a high specificity and reproducibility in the diagnosis of GH deficiency in adulthood. We propose that the heat exposure test is not used in the diagnosis of this condition in adulthood.

Adult↗
PubMed1997

Insulin-like growth factor-I, insulin, and angina pectoris secondary to coronary atherosclerosis, vasospasm, and syndrome X.

We measured growth hormone-related substances in patients with angina pectoris precipitated by different underlying disorders. Although hyperinsulinemia was more pronounced in patients with angina pectoris secondary to atherosclerotic coronary disease than in patients with syndrome X and variant angina, we found no evidence that growth hormone-related substances including insulin-like growth factor-I are associated with coronary atherosclerosis.

Angina Pectoris↗
PubMed1997

Effects of growth hormone and insulin-like growth factor-I singly and in combination on in vivo capacity of urea synthesis, gene expression of urea cycle enzymes, and organ nitrogen contents in rats.

Improvement of nitrogen balance is desirable in patients with acute or chronic illness. Both growth hormone (GH) and insulin-like growth factor-I (IGF-I) are promising anabolic agents, and their combined administration has been shown to reverse catabolism more efficiently than each of the peptides alone. This is believed to be mediated primarily through increased peripheral protein synthesis, whereas little attention has focused on a possible participation of amino acid metabolism in the liver. Four groups of rats were given: 1) placebo; 2) GH (200 micrograms/d); 3) IGF-I (300 micrograms/d); and 4) both GH and IGF-I. After 3 days, the maximum capacity of urea-nitrogen synthesis was determined by saturating infusion of alanine (n = 8 in each group), together with measurements of liver messenger RNA (mRNA) levels for urea cycle enzymes (n = 5 in each group) and N-contents of muscles, heart, and kidney. Basal plasma alpha-amino acid concentrations were similar in all groups. The capacity of urea-N synthesis [mumol/(min x 100 g body weight)] was reduced in a stepwise manner (placebo: 8.25 +/- 1.2; GH treatment: 6.52 +/- 0.8; IGF-I treatment: 5.5 +/- 0.6; and GH/IGF-I: 4.22 +/- 1.6 [P < .001 by ANOVA]), each step being lower than the former. Serum IGF-I increased stepwise from placebo (699 +/- 40 to 1,579 +/- 96 micrograms/L in the combined GH/IGF-I group), and was correlated negatively with the capacity of urea-nitrogen synthesis (P < .01). mRNA levels for urea cycle enzymes in the liver decreased after GH and IGF-I treatment, and the effect was more pronounced after the combined treatment in which the rate-limiting enzyme, argininosuccinate synthetase, was halved. Nitrogen contents of organs increased after both GH and IGF-I treatment, and even more so after the combination treatment, reaching an increase of 30% (P < .05). Data suggest that GH and IGF-I singly and, even more so in combination, additively inhibit urea synthesis. This is supposed to favor protein buildup in organs. We speculate that this inhibitory effect on the capacity of urea synthesis is caused by a decreased translation rate of the urea cycle enzymes caused by GH and IGF-I's down-regulatory effect on urea cycle enzyme gene transcription. The findings may indicate a novel mechanism of the protein anabolic action of GH and IGF-I.

Animals↗
PubMed1997

Serum leptin is increased in growth hormone-deficient adults: relationship to body composition and effects of placebo-controlled growth hormone therapy for 1 year.

The gene product from the ob gene, leptin, has recently been characterized in humans. The circulating level of leptin is related to body mass index (BMI) and more closely to estimates of total body fat, whereas visceral fat has been reported to be of minor importance. However, it is unknown if leptin is directly regulated by hormones that influence substrate metabolism and body composition. We studied leptin in adult growth hormone (GH)-deficient (GHD) patients substituted with GH treatment for 12 months in a parallel double-blind, placebo-controlled study. Twenty-seven GHD adults aged 44.9 +/- 1.9 years underwent anthropometric measurements for determination of regional and total body fat (BMI, waist to hip ratio [WHR], computed tomographic [CT] scan, dual-energy x-ray absorptiometry [DEXA] scan, and bioimpedance analysis [BIA]) before and after 12 months of placebo-controlled GH substitution (2 IU/m2) in a parallel design. The same measurements were performed in 42 healthy adults aged 39.1 +/- 1.7 years. The logarithm of serum leptin levels correlated positively with abdominal subcutaneous fat and total body fat (BIA and DEXA) in untreated GHD patients and healthy subjects. Fasting insulin did not correlate with leptin levels in either of the groups. After 12 months of GH administration, the body composition of GHD patients was significantly changed with respect to a marked decrease in body fat. The relations of leptin to the estimates of body fat were maintained, and leptin was furthermore related to BMI and fasting insulin. In multiple linear regression analyses, additional estimates of visceral adiposity (intraabdominal fat and maximal anterior-posterior diameter determined by CT scan) were significant determinants of leptin in the healthy subjects. The increase in fasting insulin levels during GH substitution correlated negatively with the reduction in leptin levels (r = -.823, P = .003). At baseline, leptin levels were increased in the patients compared with controls in both sexes (women, 21.8 +/- 3.3 v 11.3 +/- 1.4 ng/mL, P = .002; men, 8.1 +/- 1.2 v 4.7 +/- 0.7 ng/mL, P = .008). Leptin levels were similar in GHD patients treated for 12 months compared with healthy controls for both women and men (women, 15.9 +/- 2.3 and 11.3 +/- 1.4 ng/mL, P = .163; men, 7.1 +/- 2.8 and 4.7 +/- 0.7 ng/mL, P = .759). In healthy adults and in GHD patients, leptin levels were significantly higher in women than in men (11.3 +/- 1.4 v 4.7 +/- 0.7 ng/mL, P < .001; 21.8 +/- 3.3 v 8.1 +/- 1.2 ng/mL, P < .001). Gender remained a significant determinant of leptin levels in several models of multiple linear regression analysis also including age, estradiol levels, insulin, and estimates of body fat. We conclude that leptin is increased but not differently regulated in GHD patients compared with normal subjects, and that leptin levels are closely related to estimates of body fat. This relationship is maintained during a decrease in body fat due to GH substitution.

Absorptiometry, Photon↗
PubMed1997

Ketosis resistance in fibrocalculous pancreatic diabetes: II. Hepatic ketogenesis after oral medium-chain triglycerides.

A majority of patients with fibrocalculous pancreatic diabetes (FCPD) do not become ketotic even in adverse conditions. It is not clear whether this ketosis resistance is due to reduced fatty acid release from adipose tissue or to impaired hepatic ketogenesis. We tested hepatic ketogenesis in FCPD patients using a ketogenic challenge of oral medium-chain triglycerides (MCTs) and compared it with that in matched insulin-dependent diabetes mellitus (IDDM) patients and healthy controls. After oral MCTs, FCPD patients showed only a mild increase in blood 3-hydroxybutyrate (3-HB) concentrations (median: fasting, 0.13 mmol/L; peak, 0.52) compared with IDDM patients (fasting, 0.44; peak, 3.39) and controls (fasting, 0.04; peak, 0.75). Plasma nonesterified fatty acid (NEFA) concentrations were comparable in the two diabetic groups (FCPD: fasting, 0.50 mmol/L; peak, 0.79; IDDM: fasting, 0.91; peak, 1.04). Plasma C-peptide concentrations were low and comparable in the two diabetic groups. Plasma glucagon concentrations were higher in IDDM patients in the fasting state, but declined to levels comparable to those in FCPD patients after oral MCTs. Plasma carnitine concentrations were comparable in the two groups of patients. It is concluded that the failure to stimulate ketogenesis under these conditions could be partly due to inhibition of a step beyond fatty acid entry into the mitochondria.

Adipose Tissue↗
PubMed1997

Effect of graded renal ablation on kidney and serum insulin-like growth factor-I (IGF-I) and IGF binding proteins in rats: relation to compensatory renal growth.

Kidney insulin-like growth factor-I (IGF-I) increases transiently following unilateral nephrectomy, thus preceding the compensatory renal growth. The aim of the present study was to investigate the effect of different degrees (1/7 to 2/3) of renal ablation on kidney and serum IGF-I and IGF binding proteins (IGFBPs) during a 7-day study period. All nephrectomized rats exhibited an increase in the weight of the remaining renal tissue. Kidney IGF-I measured in kidney pieces close to and away from the resected area increased transiently and more significantly away from the resected area, with significant correlation to the amount of tissue resected (day 1, r = .73, P < .0001; day 2, r = .49, P < .05; and day 7, r = .48, P < .05). No changes in kidney IGFBPs or serum IGF-I were observed. Serum IGFBP-4 correlated to the degree of renal resection, as did changes in serum urea and creatinine. In conclusion, significant correlations were observed between local changes in kidney IGF-I and serum IGFBP-4 levels and the degree of renal ablation, suggesting a role for IGF-I as a renotropic factor and, further, that IGFBP-4 is removed to a major extent through the kidney.

Animals↗
PubMed1997

Hepatic amino nitrogen conversion and organ N-contents in hypothyroidism, with thyroxine replacement, and in hyperthyroid rats.

BACKGROUND/AIMS: The role of thyroid hormones in the regulation of hepatic conversions of amino nitrogen to urea is unresolved. The present study was designed to assess ureagenesis in rats with experimentally well-established hypo- and hyperthyroidism. The possible role of propylthiuracil (PTU), used for induction of hypothyroidism, was ascertained during thyroxine replacement of PTU treated hypothyroid rats. METHODS: Basal blood amino nitrogen concentrations (AAN), the urea nitrogen synthesis rate (UNSR) and the maximal hepatic capacity for urea nitrogen synthesis (CUNS) obtained during alanine infusion were determined together with N-contents in the soleus muscle and kidneys in experimentally hypothyroid rats (n = 19), upon thyroxine replacement (n = 14) and in experimentally hyperthyroid rats (n = 19). Hypothyroidism was induced by adding propylthiouracil (0.05%) to the drinking water for 5 weeks. Hyperthyroidism was induced by thyroxine 100 micrograms/100 g body weight. RESULTS: During hyperthyroidism, T3 fell to less than 10%, food intake was halved, and body weight fell by 13%. Basal blood AAN fell by 25% (p < 0.01), UNSR more than doubled (p < 0.01), and CUNS rose by 45% (p < 0.05). N-contents of the soleus muscle fell by 13% and by 20% in kidneys, respectively (p < 0.05). Thyroxine replacement normalized AAN, UNSR, CUNS and reduced N-loss to 7% in the soleus muscle (NS) and kidneys (p < 0.05), respectively. During hyperthyroidism, T3 rose five-fold, food intake rose by two thirds, and body weight fell by 10%. Basal AAN rose by 20% (p < 0.05), UNSR doubled (p < 0.01), and CUNS rose by 25% (p < 0.05). N-contents of the soleus muscle decreased by 19%, whereas kidney N-contents increased by 25% (p < 0.05). Overall liver function assessed by galactose elimination capacity did not differ among groups. Both conditions increased the rate of urea synthesis; in the hypothyroid state the hepatic waste of amino-N was limited by low blood concentration of amino-N, probably due to lower proteolysis. In the hyperthyroid state hepatic amino-N loss was aggravated by higher blood concentration of amino-N, probably due to higher proteolysis. This difference may explain the markedly different dietary nitrogen economy between the two groups. CONCLUSIONS: The findings suggest that distinct hepatic acceleration of urea synthesis may contribute to the protein loss seen in both myxedema and in thyrotoxicosis in humans.

Animals↗
PubMed1997

Moderate hyperthyroidism reduces liver amino nitrogen conversion, muscle nitrogen contents and overall nitrogen balance in rats.

There are conflicting data on the effect of thyroid hormones on nitrogen metabolism. We determined the basal blood amino nitrogen (amino-N) concentrations, the urea nitrogen (urea-N) synthesis rate and the maximum hepatic capacity of urea nitrogen synthesis during saturating infusion of alanine, in moderately acutely (24 h) and chronically (7 days) hyperthyroid rats and compared this with changes in organ nitrogen contents in muscles and kidney, nitrogen excretion and nitrogen balance. Forty-three rats were made acutely hyperthyroid through administration of 5 microg 100 g(-1) triiodothyronine twice daily (T3: 2.2 +/- 0.7 vs. 0.87 +/- 0.04 nmol L(-1), P < 0.01). Fifty-one rats were made chronically hyperthyroid through administration of 12.5 microg 100 g(-1) thyroxine twice daily (T3: 2.63 +/- 0.18 vs. 0.87 +/- 0.04 nmol L(-1), P < 0.01). Weight gain was halved in this group. Both acute and chronic hyperthyroidism increased basal blood amino-N concentration in both groups by 16% (4.5 +/- 0.15 vs. 3.9 +/- 0.13 mmol L(-1) and 4.7 +/- 0.12 vs. 3.9 +/- 0.13 mmol L(-1), respectively, P < 0.01), and decreased basal urea-N synthesis rate in both groups by 30% [2.7 +/- 0.3 vs. 4.1 +/- 0.3 micromol (min x 100 g)(-1) and 3.1 +/- 0.3 vs. 4.1 +/- 0.3 micromol (min x 100g)(-1), respectively, P < 0.01]. The capacity of urea-N synthesis during saturation fell in both groups by 35% compared with controls [6.5 +/- 0.4 vs. 9.3 +/- 0.5 micromol (min x 100 g)(-1) and 5.7 +/- 0.5 vs. 9.3 +/- 0.6 micromol (min x 100g)(-1), respectively, P < 0.01]. Nitrogen contents in the muscles, soleus and extensor digitorum longus, of chronically hyperthyroid rats decreased by 22% and 11%, respectively, whereas kidney N-content increased by 12% (P < 0.05). N-balance and urinary urea-N excretion fell by 30%, whereas faeces-N excretion increased by 80% in hyperthyroid rats. Overall liver function assessed by galactose elimination capacity did not differ among groups. Both acute and chronic moderate hyperthyroidism increase blood amino-N and decrease basal and maximum rate of urea formation. Furthermore, chronic hyperthyroidism reduces N-contents of muscles, urinary urea-N excretion and N-balance. Thyroid hormones thus mobilize muscle-N, whereas amino-N in the liver is spared from irretrievable conversion into urea.

Amino Acids↗
PubMed1997

Effect of GH/IGF-I deficiency on long-term renal changes and urinary albumin excretion in diabetic dwarf rats.

Growth hormone (GH) and insulin-like growth factor I (IGF-I) may play a role in early diabetic renal and glomerular growth and in the later development of experimental diabetic kidney disease. Rats from a genetic GH/IGF-I-deficient dwarf rat strain were made streptozotocin diabetic and were compared with nondiabetic dwarf rats. GH/IGF-I-intact rats with and without diabetes served as controls. After 6 mo of diabetes, kidney weight and total glomerular volume increased significantly in GH/IGF-I-intact diabetic rats compared with the nondiabetic GH/IGF-I-intact rats (P < 0.05), whereas the diabetic dwarf rats had insignificant changes compared with dwarf control rats. By the end of the study, urinary albumin excretion (UAE) increased from similar base levels of approximately 15-20 micrograms/24 h to 473 +/- 52 (SE) micrograms/24 h in GH/IGF-I-intact diabetic rats compared with 151 +/- 32 micrograms/24 h in diabetic dwarf rats (P < 0.01). In conclusion, isolated GH/IGF-I deficiency reduces the degree of renal and glomerular hypertrophy and the increase in UAE after 6 mo of experimental diabetes in GH/IGF-I-deficient rats.

Albuminuria↗
PubMed1997

Abdominal adiposity rather than age and sex predicts mass and regularity of GH secretion in healthy adults.

We tested the hypothesis that body composition is the major predictor of growth hormone (GH) secretion in nonobese adults. We measured lean and fat tissue distribution (computerized tomography and dual-energy X-ray absorptiometry scan) and physical fitness [maximal oxygen consumption (Vo2max)] in 42 healthy nonobese adults (22 women and 20 men, age range 27-59 yr, mean +/- SE body mass index = 24 +/- 0.5 kg/m2). Deconvolution analysis was used to estimate specific features of 24-h GH secretion and clearance. Approximate entropy was used to quantify the regularity of GH release. Older subjects exhibited decreased estimates of GH secretion compared with younger subjects. Females had higher estimates of GH secretion, a longer GH half-life, and displayed more irregularity in GH release than males. Mean 24-h serum GH concentrations correlated inversely with intra-abdominal fat and waist-to-hip ratio and positively with Vo2max. Multiple linear regression analysis revealed intra-abdominal fat as the dominant determinant of estimates of GH secretion. Vo2max was more important than sex and age in predicting GH secretion. We conclude that abdominal fat is the major determinant of GH secretion in healthy nonobese adults. Although the underlying mechanisms remain elusive, our findings extend the clinical implications of visceral adiposity to include hyposomatotropism.

Abdomen↗
PubMed1997

Serum free IGF-I during a hyperinsulinemic clamp following 3 days of administration of IGF-I vs. saline.

In a randomized crossover study in eight healthy subjects, we compared the effect of 3 days of continuous subcutaneous administration of insulin-like growth factor I (IGF-I; 10 micrograms.kg-1.h-1) and saline on fasting serum levels of free IGF-I, total (extractable) IGF-I, and IGF-binding protein (IGFBP)-1 and -3. On the 3rd day a hyperinsulinemic (euglycemic and hypoglycemic) clamp was performed. When preclamp (baseline) levels were compared after 3 days, IGF-I administration had increased total IGF-I from 225 +/- 21 (means +/- SE) to 1,003 +/- 46 micrograms/l (P < 0.0001), free IGF-I from 0.5 +/- 0.2 to 10.4 +/- 1.7 micrograms/l (P < 0.001), IGFBP-3 from 2,908 +/- 148 to 3,591 +/- 179 micrograms/l (P < 0.01), and IGFBP-1 from 7.6 +/- 3.8 to 19.6 +/- 2.5 micrograms/l (P < 0.01). During the clamp, levels of free IGF-I increased gradually from baseline to 1.0 +/- 0.3 micrograms/l (saline; P < 0.01) and to 19.6 +/- 4.7 micrograms/l (IGF-I; P < 0.005). Concomitantly, levels of IGFBP-1 decreased gradually from baseline to 4.1 +/- 2.3 micrograms/l (saline; P < 0.0005) and to 4.6 +/- 1.8 micrograms/l (IGF-I; P < 0.0001). Total IGF-I exhibited minor changes only during the clamp (P < 0.05), and IGFBP-3 was unchanged. In conclusion, administration of IGF-I increased total IGF-I about fourfold, whereas free IGF-I increased 20-fold. Noteworthily, in both situations a further twofold increase in free IGF-I was observed during the hyperinsulinemic clamp, concomitant with a decrease in IGFBP-1. This supports the hypothesis that IGFBP-1 is important in the short-term regulation of free IGF-I in vivo.

Adult↗
PubMed1997

Abdominal fat determines growth hormone-binding protein levels in healthy nonobese adults.

The circulating high affinity GH-binding protein (GHBP), which derives from the extracellular domain of the hepatic GH receptor, correlates inversely to GH levels and directly to body mass index (BMI) in healthy adults. As GH secretion and adiposity are also interrelated, we tested the hypothesis that body composition more than GH, determines GHBP levels in healthy adults. Forty-two healthy adults [21 females and 21 males; mean age, 39.4 yr range, 27-59 yr); mean BMI, 23.9 kg/m2 (range, 18.9-34.7 kg/m2)], underwent anthropometric measurements (BMI, W/H ratio, computed tomography scan, dual energy x-ray absortiometry (DEXA) scan, and bioimpedance) in addition to two GH stimulation tests (arginine and clonidine) and a 24-h GH profile. By simple linear regression, serum GHBP correlated positively to several indices of adiposity: intraabdominal fat (r = 0.537; P = 0.001), sc abdominal fat (r = 0.680; P < 0.001), BMI (r = 0.483; P = 0.001), W/H ratio (r = 0.452; P = 0.003), total body fat (DEXA scanning; r = 0.503; P = 0.002), and body fat (bioimpedance; r = 0.354; P = 0.023). Lean body mass estimated by DEXA scan was negatively associated with GHBP (r = 0.541; P < 0.001). GHBP was inversely proportional to arginine-stimulated GH release (r = -0.346; P = 0.027) and negatively associated with several measures of spontaneous GH release as estimated by deconvolution analysis (GH mass, GH production rate, and mean GH; r = -0.371; P = 0.017, r = -0.393; P = 0.011, and r = -0.343; P = 0.028, respectively)). With multiple linear regression analyses, indices of adiposity were significant determinants of GHBP levels, whereas GH status did not contribute independently to the prediction of GHBP. Neither insulin-like growth factor I nor fasting insulin levels correlated to GHBP levels. In conclusion, GHBP levels in normal adults seem to be determined by abdominal fat mass rather than GH secretion.

Abdomen↗
PubMed1997

The effect of oral glucose on serum free insulin-like growth factor-I and -II in health adults.

Insulin-like growth factor (IGF) binding protein-I (IGFBP-1) has been suggested to regulate the availability of free IGF and the glucose lowering activity of the IGF-system in relation to fuel supply. Our recent observations of significant inverse correlations between free IGF-I and IGFBP-1 in cross-sectionally collected fasting serum samples support a possible physiological association between the peptides. To further study the impact of IGFBP-1 on free IGF levels and the possible participation of the IGF-system in glucose homeostasis, we studied the time course of changes in IGFBP-1 and free IGFs in 13 healthy subjects undergoing an oral glucose tolerance test (OGTT). Serum was collected every 30 min for 330 min. Glucose, insulin, and GH followed the expected patterns and had regained baseline levels at 270 min. Total IGF-I and free and total IGF-II remained unaltered. IGFBP-1 decreased significantly by 37-52% (P < 0.05) from 150 to 210 min, whereafter the concentration gradually increased by 75% to a level that tended to be above baseline (P = 0.052). Free IGF-I decreased by 29-38% (P < 0.05) at the end of the study (270-330 min). IGFBP-1 was inversely correlated to free IGF-I at baseline (r = -0.57; P < 0.05), as well as during the OGTT (r = 0.66; P < 0.0001). In contrast, free IGF-II was not correlated to IGFBP-1. Insulin, but not free IGF-I, correlated significantly with serum glucose (P < 0.05). These results extend our previous findings of an inverse correlation between free IGF-I and IGFBP-1 in cross-sectional studies to include longitudinal observations, and thus further substantiates the hypothesis that IGFBP-1 is an important determinant of free IGF-I in vivo. Significant changes in free IGF-I were observed only in the late postprandial phase, when glucose and insulin were fully normalized, demonstrating that free IGFs probably do not participate in glucoregulation to any significant degree during an oral glucose load in healthy subjects.

Administration, Oral↗