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Biomedical subjects

N Moller

Publications and source records attributed to N Moller.

At least 19 recordsLinked to original sources
PubMed1999

Whole body protein kinetics using Phe and Tyr tracers: an evaluation of the accuracy of approximated flux values.

Phenylalanine (Phe) kinetics are increasingly used in studies of amino acid kinetics, because the metabolic fate of Phe is limited to incorporation into protein (protein synthesis, Sp) and catabolism via hydroxylation (Qpt) to tyrosine (Tyr). Besides an infusion of labeled Phe to measure Phe flux (Qp), a priming dose of Tyr and an independent Tyr tracer are used to measure Tyr flux (Qt) and Qpt. Alternatively, Qt, Qpt, and Sp can be approximated by using equations, based on Phe and Tyr concentrations in body proteins, that eliminate the need for a Tyr tracer. To evaluate the accuracy of this approach, data were obtained from 12 type I diabetic patients and 24 nondiabetic control subjects who were studied with the full complement of tracers both with and without insulin infusion. Sp approximations closely matched measured values in both groups (mean difference <2%, all values <5%), but the agreement was poor for Qpt (error range = -8 to +43%) and Qt (error range -22 to +41%). Insulin status had no effect on these comparisons. The lower approximation error for Sp vs. Qpt is due to the small contribution ( approximately 10%) of Qpt to Qp. Approximation error for Qpt (r > 0.99) can be explained by variability in the ratio of Tyr to Phe coming from protein breakdown, (Qt - Qpt)/Qp. Ideally, all fluxes should be directly measured, but these data suggest that whole body Sp can be approximated with an acceptably small margin of error. However, the same equations do not yield reliably accurate values for Qpt or Qt.

Adult↗
PubMed1998

Disruption of the relationship between fat content and leptin levels with aging in humans.

Leptin released from adipose tissue is believed to participate in a negative feedback loop regulating appetite, and malfunction of this mechanism could lead to obesity. We measured plasma leptin and body composition (dual energy x-ray absorptiometry) in 70 healthy subjects, divided into 3 age groups (young, 25 +/- 1 yr; middle-aged, 53 +/- 1 yr; old, 70 +/- 1 yr), while on a 5-day weight-maintaining diet. Pairwise correlations were assessed using product-moment correlation, and regression analysis was used to evaluate relationships between leptin and other variables. Leptin concentrations and relative body fat content were correlated in young females (r = 0.71; P = 0.009) and in young males (r = 0.76; P = 0.007), but not in the combined middle-aged and elderly groups (r = 0.19; P = 0.36 and r = 0.19; P = 0.38 in females and males, respectively). Regression analysis showed a clear correlation between circulating leptin and relative fat mass in the young subjects (P = 0.0001), but not in the older subjects (P = 0.199). We conclude that body fat content in young subjects correlates with plasma leptin in both genders, whereas this relationship is disrupted in elderly subjects, thus possibly contributing to the obesity occurring with age.

Absorptiometry, Photon↗
PubMed1997

Myocardial insulin resistance in patients with syndrome X.

Insulin resistance is common in patients with angina pectoris, a positive exercise electrocardiogram, and normal coronary angiograms (syndrome X). It is still not known whether insulin resistance affects the cardiac muscle itself and, if so, whether insulin resistance involves myocardial hemodynamics and energy metabolism. We investigated hemodynamics as well as metabolite exchanges across the heart and the forearm in eight patients with syndrome X and eight control subjects during a baseline period after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Myocardial hemodynamics and metabolism were studied at rest, during pace stress, and in the recovery period after pacing. Neither coronary sinus blood flow nor forearm blood flow differed between the groups before and during the clamp. Whole body insulin-stimulated glucose uptake was decreased in the patients (15.6+/-2.1 vs. 23.1+/-2.0 micromol x kg-1 x min-1). Insulin-stimulated glucose uptake in the forearm and the cardiac muscle was equally reduced in the patients (46+/-5 and 48+/-5%). Myocardial glucose uptake correlated with total arterial delivery in the control subjects (r = 0.63, P < 0.01), but not in patients (r = 0.22, P = 0.13). Carbohydrate and lipid oxidation was similar in the two groups at rest, and changes during the clamp were not different in control subjects and patients either at rest, during pacing, or in the recovery period. Patients with syndrome X exhibit myocardial insulin resistance, but cardiac energy metabolism remains unaffected. In patients with syndrome X, insulin-stimulated glucose uptake is independent from myocardial blood flow.

Blood Glucose↗
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↗
PubMed1993

Marked effects of sustained low growth hormone (GH) levels on day-to-day fuel metabolism: studies in GH-deficient patients and healthy untreated subjects.

The metabolic effects of circadian GH levels in the very low physiological range are unknown. Therefore, we studied 1) GH-deficient patients on receiving GH replacement therapy in whom the last GH injection was replaced with a constant iv infusion starting at 24 h of either GH (35 micrograms/h) or saline (SAL), and 2) an untreated healthy control group. Glucose turnover, indirect calorimetry, and forearm exchange of metabolites were investigated the following day in the basal state (8-11 h) and during a euglycemic (11-13 H) and a hypoglycemic (13-14 h) glucose clamp. During infusion, steady state GH levels increased by 1.9 micrograms/L. Basal and insulin-stimulated energy expenditures (EE) were lower in the patients during SAL than during GH infusion, and the basal respiratory exchange ratio was also lower during GH treatment. Protein EE was elevated during SAL compared to GH infusion (P < 0.05). During the clamp, forearm glucose uptake decreased in the GH study compared to that in the SAL study ((P < 0.05). The patients in the SAL study were more sensitive to insulin during the clamp in terms of suppression of endogenous glucose production (EGP; P < 0.05) and infusion rate of glucose necessary to maintain euglycemia (M value; P < 0.01). Lipid oxidation, in particular in the basal state, was decreased during SAL compared to GH infusion (P < 0.01). The SAL-treated compared with the control group was characterized by decreased basal and insulin-stimulated EE (P < 0.01), increased protein EE (P < 0.01), and hypersensitivity to insulin in terms of suppression of EGP (P < 0.05) and M value (P < 0.01). During the hypoglycemic clamp, the patients in the SAL study were hypersensitive to the hypoglycemic actions of insulin in terms of increased M-value and suppression of EGP, and lipolysis was impaired, as judged by the inhibition of net forearm uptake of FFA. In conclusion, very low GH levels exert powerful actions on day-to-day metabolism, resulting in protein and glucose sparing at the expense of lipids.

Adult↗
PubMed1993

Normal basal and insulin-stimulated fuel metabolism in lean women with the polycystic ovary syndrome.

Many reports have suggested that hyperandrogenaemic patients with the polycystic ovary syndrome (PCOS) may be insulin resistant. However, there have also been suggestions that their insulin resistance may relate to obesity and android fat distribution. To assess whether PCOS induces metabolic disturbances independently of obesity, we studied seven lean patients with PCOS (age, 27.1 +/- 2.0 yr; body mass index, 22.2 +/- 0.78 kg/m2; waist/hip ratio, 0.79 +/- 0.02; fat-free mass, 46.38 +/- 1.13 kg) and seven normal women (age, 25.7 +/- 1.4 yr; body mass index, 21.3 +/- 0.69 kg/m2; waist/hip ratio, 0.74 +/- 0.02; fat-free mass, 50.1 +/- 1.51 kg) for 3 h in the basal period and 2 h during a hyperinsulinemic (0.4 mU/kg.min) euglycemic clamp. In the basal state, comparable metabolic indices were recorded: serum insulin, 35.9 +/- 7.7 (PCOS) vs. 37.3 +/- 2.87 pmol/L (controls); plasma C-peptide, 364.1 +/- 66.2 vs. 397.2 +/- 66.2 pmol/L; plasma glucose, 4.95 +/- 0.09 vs. 4.77 +/- 0.09 mmol/L; forearm arterio-venous difference in glucose, 0.17 +/- 0.04 vs. 0.15 +/- 0.07 mmol/L; isotopically determined endogenous glucose production, 1.9 +/- 0.1 vs. 2.0 +/- 0.1 mg/kg.min; and serum nonesterified fatty acids, 545 +/- 40 vs. 617 +/- 54 mumol/L (all P > 0.05). During the clamp, all recordings were again similar: serum insulin, 282.7 +/- 21.5 vs. 270.5 +/- 13.6 pmol/L; plasma C-peptide, 331.0 +/- 33.1 vs. 364.1 +/- 66.2 pmol/L; plasma glucose, 4.99 +/- 0.07 vs. 4.99 +/- 0.05 mmol/L; glucose arterio-venous difference, 1.01 +/- 0.18 vs. 0.85 +/- 0.12 mmol/L; endogenous glucose production, -0.9 +/- 0.1 vs. -0.5 +/- 0.2 mg/kg.min; amount of exogenous glucose necessary to maintain euglycemia, 4.0 +/- 0.4 vs. 3.8 +/- 0.5 mg/kg.min; and nonesterified fatty acids, 205 +/- 7 vs. 246 +/- 18 mumol/L (all P > 0.05). By showing normal basal and insulin-stimulated substrate metabolism in lean hyperandrogenemic PCOS patients, these data suggest that insulin resistance may be an epiphenomenon, rather than a primary feature of PCOS.

Adult↗
PubMed1993

Estimates of insulin action in normal, obese and NIDDM man: comparison of insulin and glucose infusion test, CIGMA, minimal model and glucose clamp techniques.

Many methods of varying complexity are available for the measurement of insulin resistance (action) in man. No study has previously compared several of these in the same subjects to establish which is the most appropriate for routine use. We have, therefore, compared six methods: the hyperinsulinemic eu(iso)-glycaemic clamp (Eu), insulin glucose infusion test (IGI), hyperglycaemic clamp (Hy), continuous infusion of glucose with model assessment (CIGMA), minimal model (Min) and modified minimal model (Mod). Nineteen subjects with varying degrees of glucose tolerance were studied. Eight normal (BMI 22.5 +/- 1.5 kg/m2), six obese (BMI 38 +/- 5 kg/m2) and five NIDDM subjects (BMI 27 +/- 3 kg/m2) were investigated, in a randomized fashion, on separate days. The ratio of metabolic clearance rate of glucose (MCRG) and Insulin (I) was used as the measure of insulin action during Eu, Hy and IGI. Si was calculated as the index of insulin sensitivity from (Min) and (Mod) and CIGMA was obtained as previously described. MCRG was converted to Si to allow for direct comparison with (Min). Methods requiring incremental endogenous insulin secretion (which was highly variable) to calculate an index of insulin action (Si Min, Si Hy and CIGMA) failed to find an overall difference between groups. Only Si Eu (p = 0.007) and Si IGI (p = 0.001) demonstrated a significant overall group difference when Si was used. When MCRG/I was used, Eu, IGI and Hy were able to distinguish a significant overall group difference. With the exception of CIGMA and SiHy all other methods found a significant difference in insulin action between normals and NIDDM subjects. Only Eu and IGI could distinguish obese from normal, while only Si Min, could distinguish obese from NIDDM subjects. Eu and IGI were the only methods to be significantly correlated: normals Rs = 0.75, p < 0.05, obese Rs = 0.9, p < 0.05, and NIDDM Rs = 1.0, p < 0.05. In conclusion we have demonstrated that: 1) The insulin-glucose infusion test and the eu(iso)glycaemic clamp were significantly correlated in normals, obese and NIDDM subjects. 2) Only the eu(iso)glycaemic clamp and insulin glucose infusion test could significantly separate obese from normal subjects. 3) the IGI appears to be a practical, simple and precise method for measuring in vivo insulin action in man and gives results closely similar to those found with the hyperinsulinemic eu(iso)glycaemic clamp.

Adult↗
PubMed1989

Continuous infusion of octreotide in acromegaly.

15 patients with acromegaly were treated with continuous subcutaneous infusion of octreotide in increasing dose from 200 to 1600 micrograms per 24 h by 200 micrograms increments each week. Patients were studied during the initial 7 h of infusion, weekly at each dose level, then after 1 and 2 months at maximum dosage. 13 patients responded well, as judged by growth hormone (GH) suppression and return of insulin-like growth factor 1 to normal, although 1 patient withdrew due to adverse effects; 2 patients showed no significant reduction in GH. In the 12 responders GH level fell within the first 3 h of infusion at a mean plasma octreotide level of 0.76 (SE 0.26) micrograms/l, corresponding to 25 micrograms of infused drug. Optimum suppression of GH occurred at a dosage of 600 micrograms per 24 h, a plasma drug level of 3.5 (0.5) micrograms/l. A definite reduction in tumour size was seen on computerised tomographic scan in 2 patients. All responders noted subjective improvement in acromegalic symptoms. Adverse effects comprised gastrointestinal disturbances, which were transient and mild in 14 patients but severe in 1; biliary sludging occurred in 1 patient. No significant deterioration in carbohydrate tolerance was seen in the responders.

Acromegaly↗
PubMed1978

Solvent deposition method for enhancement of dissolution rate: importance of drug-to-excipient ratio.

Dissolution rates and particle sizes of phenylbutazone solvent deposited on lactose, starch, and silicon dioxide, separately, and of norethindrone and digoxin deposited on lactose were investigated. Microparticulate dispersed drugs on the surface of excipients result when drug-to-excipient ratios are low. Fast dissolution rates are observed for such systems. This effect can be extended to higher ratios when silicon dioxide is used as the excipient. Because of adsorption, however, the release from silicon dioxide is more or less limited.

Chemical Precipitation↗