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Biomedical subjects

M Frölich

Publications and source records attributed to M Frölich.

At least 19 recordsLinked to original sources
PubMed1992

In vivo insulin responsiveness for glucose uptake and production at eu- and hyperglycemic levels in normal and diabetic rats.

UNLABELLED: Whole body glucose uptake (BGU) and hepatic glucose production (HGP) at maximal plasma insulin concentrations (+/- 5000 microU/ml) were determined by eu- (EC) (6 mM) and hyperglycemic (HC) (20 mM) clamps (120 min), combined with [3-3H]glucose infusion, in normal and streptozotocin-treated (65 mg/kg) 3-day diabetic, conscious rats. In normal rats, during EC, BGU was 12.4 +/- 0.4 mg/min and during HC, when urinary glucose loss was 0.54 +/- 0.09 mg/min, BGU was 25.5 +/- 1.6 mg/min. However, throughout the final 60 min of HC, glucose infusion rate (GIR) was not constant but a linear decline in time (r = -0.99) of 17%, P less than 0.0001, was observed indicating a hyperglycemia-induced desensitization process. In diabetic rats, during EC, BGU was 7.7 +/- 0.3 mg/min and during HC, BGU was 15.5 +/- 1.4 mg/min. Throughout the final 60 min of HC, GIR was constant, suggesting that the hyperglycemia-induced desensitization process was already completed. In normal and diabetic rats, HGP was similar: during EC 0.2 +/- 0.5 mg/min and 0.1 +/- 0.5 mg/min, and during HC 0.4 +/- 0.4 mg/min and 0.5 +/- 0.6 mg/min, respectively. In vitro adipocyte and muscle insulin receptor studies showed normal to increased receptor number and increased receptor autophosphorylation in diabetic compared to normal rats. IN CONCLUSION: (i) 3-day diabetic rats show, at maximal plasma insulin concentrations, insulin resistance to BGU, but not to HGP. The resistance to BGU is equally present (reduction of 38%) at eu- and hyperglycemic levels as compared to normal rats. (ii) 3-day diabetic rats reveal no defect in adipocyte and muscle insulin receptor function. These data indicate that the diabetes induced insulin resistance for BGU is at the post-receptor level and due to a decreased maximal capacity (Vmax) for glucose uptake, with no change in affinity, or Km.

Adipose Tissue↗
PubMed1992

Preexisting cardiopulmonary disease attenuating the atrial natriuretic peptide response. Results in patients with acute respiratory failure.

The purpose of this study was to evaluate the pathophysiologic role of atrial natriuretic peptide (ANP) as a pulmonary artery vasodilator in patients with acute respiratory failure receiving artificial ventilation. Twenty-one consecutive patients were studied, 12 without and 9 with preexisting cardiopulmonary disease. Pulmonary artery plasma ANP levels were significantly higher than the levels obtained in the superior vena cava and radial artery. Plasma ANP levels correlated significantly with the plasma levels of its second messenger, guanosine 3',5'-cyclic monophosphate (cGMP). In the 12 patients without prior cardiopulmonary disease, plasma ANP levels correlated significantly with mean pulmonary arterial pressure (MPAP). This correlation was not found in the nine patients with preexisting cardiopulmonary disease. The cGMP/ANP ratio, indicating the biologic effect of ANP, was also higher in the patients without preexisting cardiopulmonary disease. These results are compatible with clearance and vasodilator activity of ANP in the pulmonary vascular bed, but only in patients without preexisting cardiopulmonary disease.

Acute Disease↗
PubMed1992

[The tenacity of Newcastle disease virus (LaSota) in the excrement of laying hens in different housing systems].

The survival time of NDV (LaSota) in the excrement of layers was in summer (winter) 22 and 18 days (26 and 36 days) in two cage houses, 14 and 18 days (36 and 33 days) in two floor-pen houses, as well as 8 days (54 and 68 days) in two dropping store places. By one week staying in battery cages and following the storage in dropping store place after 47 or 50 days NDV (LaSota) could not be reisolated. Besides environment factors, temperature, pH and dry matter was the thermic effect very significant. The comparison of the tenacity of NDV (LaSota) in different housing systems was besides of the quantitative determination of survival time supported through the application of a life time distribution test.

Animals↗
PubMed1992

Fluoxetine increases insulin action in obese nondiabetic and in obese non-insulin-dependent diabetic individuals.

Insulin resistance contributes to the metabolic defects in non-insulin-dependent diabetes mellitus (NIDDM). Anorectic agents have been shown to improve insulin action in NIDDM, irrespective of weight reduction. The serotonin-reuptake inhibiting agent fluoxetine has recently been recognized as an anorectic agent. The effect of fluoxetine on insulin action has not yet been determined. In a double blind placebo controlled crossover study, we examined hepatic and peripheral insulin action by the sequential hyperinsulinemic euglycemic clamp technique with infusion of 3-3H-glucose in eight obese NIDDM and in eight obese nondiabetics, matched for age, sex and body mass index. Body weight was kept constant. After 14 days of fluoxetine, 60 mg daily, in NIDDM half-maximal peripheral glucose uptake was achieved at a lower insulin level than after placebo (ED50pgu 180.5 +/- 25.8 vs 225.3 +/- 39.9 mU/l, P less than 0.05), but not in nondiabetics (140 +/- 15.3 vs 135.3 +/- 22.2 mU/l, n.s.). Maximal peripheral glucose uptake (Vmaxpgu) did not change significantly. Basal hepatic glucose production (HGP) was reduced after fluoxetine in both NIDDM (9.45 vs 10.37 mumol/kg/min) and in nondiabetics (8.57 vs 9.16 mumol/kg/min), although the difference was only significant in nondiabetics (P less than 0.05). Multivariate analysis disclosed no differences in the effect of fluoxetine between NIDDM and nondiabetics. When nondiabetics and NIDDM were considered together, only the most insulin-resistant individuals demonstrated a decrease in ED50pgu (P less than 0.001). Likewise, only the individuals with the most outspoken hepatic insulin resistance demonstrated a decrease in insulin level, at which hepatic glucose production is completely suppressed (HGP0) (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

C-Peptide↗
PubMed1992

Fluoxetine increases insulin action in obese type II (non-insulin dependent) diabetic patients.

Insulin resistance contributes to the metabolic defects in non-insulin dependent diabetes mellitus (NIDDM). Anorectic agents have been shown to improve insulin action in NIDDM, irrespective of weight reduction. In a double-blind placebo-controlled cross-over study, we examined hepatic and peripheral insulin action by the sequential hyperinsulinaemic-euglycaemic clamp technique with infusion of 3-[3H]-glucose in eight obese NIDDM patients and in eight obese non-diabetics, matched for age, sex and body mass index. Body weight was kept constant. After 14 days of fluoxetine, 60 mg daily, in NIDDM half-maximal peripheral glucose uptake was achieved at a lower insulin level than after placebo (ED50pgu: 180.5 +/- 25.8 vs. 225.3 +/- 39.9 mU/l, P < 0.05), but not in non-diabetics (140 +/- 15.3 vs. 135.3 +/- 22.2 mU/l, n.s.). Maximal peripheral glucose uptake (Vmaxpgu) did not change significantly. Multivariate analysis disclosed no differences in the effect of fluoxetine between NIDDM and non-diabetics. When non-diabetics and NIDDM were considered together, only the most insulin-resistant individuals demonstrated a decrease in ED50pgu (P < 0.001). Likewise, only the individuals with the most outspoken hepatic insulin resistance demonstrated a decrease in insulin level, at which hepatic glucose production (HGP) is completely suppressed (HGP0) (P < 0.01). In conclusion, fluoxetine improves peripheral and hepatic insulin action in obese insulin-resistant subjects irrespective of its weight lowering effect.

Blood Glucose↗
PubMed1992

Tetrapolar body impedance is influenced by body posture and plasma sodium concentration.

Tetrapolar body impedance measures body resistance, which is highly correlated to total body water and fat-free mass. We investigated the change in resistance measured with tetrapolar impedance, resulting from fluid shifts, following an altered body posture and changes in resistance following an altered electrolyte composition of the extracellular fluid during hypertonic saline and mannitol infusion. An increase in body resistance was measured during recumbency, which was positively correlated with the calculated shift of interstitial fluid to the intravascular space. This effect was completely abolished after 5 min in the upright position. During infusion of 5% saline or 20% mannitol the change in resistance and the change in plasma sodium concentration were inversely correlated. Therefore the measurement of resistance is essentially influenced by alterations in the amount and composition of extracellular fluids. Using the resistance measurements standardization is obligatory for posture and plasma sodium concentration. This is particularly important when repeated measurements are performed.

Adult↗
PubMed1991

Amylin-induced in vivo insulin resistance in conscious rats: the liver is more sensitive to amylin than peripheral tissues.

UNLABELLED: Amylin is a polypeptide of 37 amino acids, predominantly synthesized in pancreatic Beta cells. The peptide was suggested to be dysregulated in Type 2 (non-insulin-dependent) diabetes mellitus and it antagonized certain actions of insulin in vitro in rat muscle. This led to speculation that amylin is involved in the pathogenesis of Type 2 diabetes. We have examined the in vivo effects of rat amylin, amidated at the carboxy-terminus, on insulin-mediated carbohydrate metabolism in conscious rats, using the hyperinsulinaemic (+/- 1 nmol/l) euglycaemic (6 mmol/l) clamp technique combined with [3-3H]-glucose infusion. Basal plasma amylin levels were less than or equal to 75 pmol/l. Applied amylin levels of 220 +/- 75 pmol/l (infusion rate of 12.5 pmol/min) antagonized only the insulin action on liver, resulting in a 100% increase of hepatic glucose output. Amylin levels of 4750 +/- 750 pmol/l (infusion rate of 125 pmol/min) induced a 250% increase of insulin-inhibited hepatic glucose output and, in addition, a 30% decrease of insulin-stimulated peripheral glucose up-take. Amylin did not affect: 1) the metabolic clearance rate of insulin, 2) the levels of plasma glucagon, epinephrine, norepinephrine, and corticosterone, 3) in vitro insulin binding and insulin-stimulated receptor autophosphorylation. This suggests that amylin antagonizes insulin action via binding to a yet unknown receptor. IN CONCLUSION: amylin causes in vivo insulin resistance and the liver seems the predominant organ regulated by this hormone. The in vivo effects of amylin mimic the pathophysiological abnormalities of insulin action in Type 2 diabetes.

Amyloid↗
PubMed1991

Serum osteocalcin levels before and after 1,25 dihydroxy-vitamin D stimulation in a family with hypophosphatasia.

Because defective bone mineralization occurs in hypophosphatasia (HP) and the source of bone alkaline phosphatase is the osteoblast, we investigated another marker of osteoblast activity, namely the production of osteocalcin in an HP family and controls. The mean basal osteocalcin levels in the two affected young adults and their parents (the apparent heterozygotes) were 3.4 ng/ml (range 2.5-4.6) and were not different from the levels in age- and sex-matched controls (3.6 ng/ml; range 2.5-4.6). Furthermore, the ratio of carboxylated to total osteocalcin was normal. The rise in osteocalcin after 1,25-dihydroxycholecalciferol stimulation (2 micrograms daily for one week) was slightly greater in the controls than in the HP family. These results support the concept that there is no global defect in osteoblast function in this family with HP.

Adult↗
PubMed1991

Influence of angiotensin converting enzyme inhibition on pump function and cardiac contractility in patients with chronic congestive heart failure.

Eleven patients with coronary artery disease and chronic heart failure were studied before and three months after the angiotensin converting enzyme inhibitor enalapril was added to their frusemide medication. The following were measured: left ventricular pressure and volume with transient occlusion of the inferior vena cava, radionuclide angiography, and hormone concentrations in plasma. As in other reported studies, the clinical condition of the patients improved and their exercise tolerance increased moderately. Addition of enalapril reduced end diastolic and systolic pressure, reduced ventricular volume, and concomitantly increased the ejection fraction. The end systolic pressure-volume relation shifted to the left as it did in a similar animal study. In the animal study unloading by a vasodilator did not induce a leftward shift, so it can be inferred that in the present study unloading combined with a decrease in the angiotensin concentration was instrumental in remodelling the heart. Though unloading was expected to have a beneficial effect on the oxygen supply/demand ratio of the heart, the patients still showed the same drop in the ejection fraction during exercise as they did before treatment with enalapril, and early diastolic filling did not improve. Normally, regression of cardiac dilatation is only found if pump function improves; the present study showed that unloading in combination with angiotensin converting enzyme inhibition reshapes the ventricle without improving intrinsic pump function.

Aged↗
PubMed1991

Whole body and hepatic insulin action in normal, starved, and diabetic rats.

In normal (N), 3-days starved (S), and streptozotocin-treated (65 mg/kg) 3-days diabetic (D) rats we examined the in vivo dose-response relationship between plasma insulin levels vs. whole body glucose uptake (BGU) and inhibition of hepatic glucose production (HGP) in conscious rats, as determined with the four-step sequential hyperinsulinemic euglycemic clamp technique, combined with [3-3H]glucose infusion. Twelve-hour fasting (basal) HGP was 3.0 +/- 0.2, 2.1 +/- 0.2, and 5.4 +/- 0.5 mg/min in N, S, and D rats, respectively. Next, all rats were clamped at matched glycemia (6 mM). Lowering plasma glucose in D rats from +/- 20 to 6.0 mM did not increase plasma norepinephrine, epinephrine, glucagon, and corticosterone levels. For BGU, insulin sensitivity was increased (70 +/- 11 microU/ml) in S and unchanged (113 +/- 21 microU/ml) in D compared with N rats (105 +/- 10 microU/ml). Insulin responsiveness was unchanged (12.4 +/- 0.8 mg/min) in S and decreased (8.5 +/- 0.8 mg/min) in D compared with N rats (12.3 +/- 0.7 mg/min). For HGP, insulin sensitivity was unchanged (68 +/- 10 microU/ml) in S and decreased (157 +/- 21 microU/ml) in D compared with N rats (71 +/- 5 microU/ml). Insulin responsiveness was identical among N, S, and D rats (complete suppression of HGP). In summary, 1) insulin resistance in D rats is caused by hepatic insensitivity and by a reduction in BGU responsiveness. 2) S rats show normal hepatic insulin action, but insulin sensitivity for BGU is increased. Therefore, S and D rats both suffering from a comparable catabolic state (10-15% body wt loss in 3 days) show opposite effects on in vivo insulin action. This indicates that in vivo insulin resistance in D rats is not caused by the catabolic state per se.

Animals↗
PubMed1991

Pulsatile thyrotropin release and thyroid function in acromegalics before and during subcutaneous octreotide infusion.

The pulsatile secretion of TSH was studied in eight patients with active acromegaly before treatment and after 1 month of therapy consisting of the sc infusion of 300 micrograms octreotide/day. Mean GH levels decreased from 37.1 +/- 7.2 to 5.2 +/- 1.4 mU/L (P = 0.002). Insulin-like growth factor-I levels decreased from 82.9 +/- 8.8 to 37.8 +/- 9.8 nmol/L (P less than 0.01) and normalized in five of the eight patients. In one patient TSH levels were undetectable before and during octreotide therapy. In the other seven patients, Cluster analysis revealed 11.9 +/- 0.8 pulses/24 h, with a mean pulse width of 81 +/- 4.6 min, a mean pulse height of 1.33 +/- 0.42 mU/L, and a mean pulse increment of 0.36 +/- 0.12 mU/L. During octreotide therapy these pulse parameters remained unchanged. Pulse height and amplitude increased significantly during the night (i.e. from 2000-0800 h) in both untreated and treated patients. The acrophase was unchanged by therapy. During therapy T3 levels decreased from 2.05 +/- 0.17 nmol/L to 1.44 +/- 0.08 nmol/L (P = 0.001), while rT3 levels increased from 0.14 +/- 0.02 nmol/L to 0.19 +/- 0.03 nmol/L (P less than 0.05). Plasma T4 levels remained unchanged. From these studies we conclude that the TSH pulse generator is unchanged in active acromegaly and apparently unaffected by chronic octreotide infusions.

Acromegaly↗
PubMed1991

Octreotide treatment in acromegaly: a comparison between pen-treated and pump-treated patients in a cross-over study.

The effect of a schedule of three daily injections of 100 micrograms octreotide (pen treatment) compared with that of a continuous sc infusion of 300 micrograms/24 h on GH and IGF-I suppression, and other GH-dependent parameters was studied in 10 acromegalic patients in a cross-over study. Treatment was administered via a specially designed pen or a pump for 4 weeks. Following a washout period of a further 4 weeks, patients were switched to the other mode of delivery. Mean GH levels decreased from 26.2 +/- 4.7 to 9.9 +/- 3.1 mU/l (p = 0.007) during pen therapy and to 7.7 +/- 2.4 mU/l (p = 0.003) during pump treatment. IGF-I levels decreased from 75.6 +/- 9.5 to 42.0 +/- 9.3 nmol/l (p = 0.003) during pen treatment and to 32.5 +/- 2.5 nmol/l (p = 0.001) during pump treatment. There was a significant difference in IGF-I levels between pen and pump treatments (p = 0.03). In 7 patients the IGF-I levels normalized during pump treatment compared with 3 patients in the pen treatment group. There was no change in the free T4 index levels, but the free T3 index significantly decreased during therapy, without changes in plasma TSH. This study demonstrates that continuous infusion with octreotide results in a better control of GH oversecretion than the intermittent mode of delivery.

Acromegaly↗
PubMed1991

The interaction of GHRH with TRH in acromegaly: a controlled study.

In a single-blind placebo-controlled study, the effect of an iv bolus injection of 100 micrograms GHRH(1-29)NH2 on the response to 200 micrograms TRH was assessed in 10 untreated patients with acromegaly to determine whether GHRH interacts with TRH in acromegaly, as previously described in healthy subjects. The combination of GHRH(1-29)NH2 with TRH resulted in a larger increment of peak and of integrated plasma TSH and PRL levels than after TRH alone. GHRH alone had no effect on TSH secretion and only a modest effect on PRL secretion. These findings suggest that in acromegaly, like in healthy individuals, GHRH potentiates the TSH response to TRH and that the effects of GHRH and TRH on PRL secretion are additive.

Acromegaly↗
PubMed1991

Plasma atrial natriuretic peptide concentrations in patients weaning from positive-pressure ventilation.

The effect of positive-pressure ventilation on plasma atrial natriuretic peptide (ANP) concentrations was investigated in sixteen patients weaning from the ventilator. During spontaneous ventilation plasma ANP concentrations rose significantly from 59 (16-270) to 67 (13-320) pg/ml (median and range, P less than 0.05) and mean arterial blood pressure rose from 84 +/- 3 to 92 +/- 3 mmHg (mean +/- SEM, P less than 0.05) if compared with periods of positive-pressure ventilation. This increase in plasma ANP concentrations occurred irrespective of the underlying disease and the wide scatter of the ANP plasma levels found in individual patients. As right atrial stretch is the major stimulus for the release of the ANP the data indicate a decrease in cardiac output during positive-pressure ventilation following an impaired central venous return to the heart.

Adult↗
PubMed1990

Comparative enantioselective pharmacokinetic studies of celiprolol in healthy volunteers and patients with impaired renal function.

The pharmacokinetics of the beta 1-selective adrenergic antagonist (R,S)-celiprolol has been studied after oral administration of 200 mg celiprolol-HCl to 8 healthy volunteers and 8 patients with various degrees of impaired renal function. No significant difference was found between the two enantiomers in the control group or in the patients. In healthy volunteers an average of 9.8% of the dose of R-(+)-celiprolol and 9.5% of S-(-)-celiprolol was recovered unchanged in the urine. Renal impairment reduced the urinary excretion of both enantiomers to the same extent according to the severity of the uraemia, producing higher AUCs. Nevertheless, the terminal half-lives of the R- and S-enantiomers were not significantly different between the groups. Dosage reduction in patients with renal impairment does not seem to be necessary.

Administration, Oral↗
PubMed1990

The influence of octreotide treatment on pulsatile growth hormone release in acromegaly.

The pulsatile release of GH was investigated in eight active acromegalic patients before and during a subcutaneous infusion of 300 micrograms octreotide/24 h for 4 weeks. The number of GH pulses increased from a basal value of 14.4/24h to 16.3/24h during octreotide therapy. At the same time the mean GH concentration, valley concentration, peak height and amplitude decreased significantly. The inhibitory effect of octreotide on pulse characteristics did not depend on the time of day. IGF-I levels also decreased significantly; in five patients normal levels were reached. IGF-I levels correlated significantly with the mean GH level (r = 0.714, P less than 0.001), mean valley concentration (r = 0.697, P less than 0.001) and, to a lesser extent, area under the curve (r = 0.436, P = 0.033), but not the number of pulses. Plasma octreotide levels did not correlate with pulse parameters. In all but one patient a circadian rhythm was present during both the basal study and octreotide therapy. Compared with surgically treated acromegalics, the number of GH pulses was higher in untreated and octreotide-treated patients. This study demonstrates the pulsatile release of GH in active acromegaly both before and during octreotide therapy. This result suggests that endogenous GHRH is important for the generation of GH pulses in this disease.

Acromegaly↗