Biomedical subjects

P Nowotny

Publications and source records attributed to P Nowotny.

At least 73 records · Page 4Linked to original sources

PubMed1997

Increase by tri-iodothyronine of endothelin-1, fibronectin and von Willebrand factor in cultured endothelial cells.

Hyperthyroidism is associated with elevated plasma levels of endothelium-derived proteins such as von Willebrand factor (vWF), fibronectin (FN) and endothelin-1 (ET-1). This study was designed to characterize the mechanisms involved in this phenomenon at the cellular level. vWF, FN and ET-1 secretion and mRNA expression were measured in human umbilical vein endothelial cells (HUVECs) exposed to tri-iodothyronine (T3) for 13 +/- 1 days, using ELISA, Western blot, RIA and Northern blot analysis respectively. Exposure of HUVECs to T3 significantly increased vWF secretion (50 ng T3/ml: 117 +/- 5%, P < 0.01; 100 ng T3/ml: 127 +/- 26%, P < 0.01) as well as vWF mRNA expression (50 ng/ml: 116 +/- 13%, P < 0.001; 100 ng/ml: 136 +/- 30%, P < 0.002) (results are means +/- S.D. analysed by the Wilcoxon signed rank test). FN secretion was significantly affected by 50 (145 +/- 42% of control, P < 0.05) and 100 (116.8 +/- 16% of control, P < 0.05) ng T3/ml, and FN mRNA expression by 50 ng T3/ml (123 +/- 20%, P < 0.05). Long-term incubation with T3 increased both ET-1 secretion (25 ng/ml: 124 +/- 25%, P < 0.001; 50 ng/ml: 165 +/- 53%, P < 0.05; 100 ng/ml: 116 +/- 17%, P < 0.05) and prepro-ET-1 mRNA expression (25 ng/ml: 112 +/- 16%, P < 0.05; 50 ng/ml: 134 +/- 43%, P < 0.02; 100 ng/ml: 120 +/- 20%, P < 0.02). Protein kinase C (PKC) isoforms epsilon and beta II were not significantly affected by T3, whereas PKC alpha was increased in whole cell lysates and in membrane fractions of cells incubated with 100 but not 50 ng T3/ml. Prepro-ET-1 mRNA stability, cell numbers and proliferation, measured by [3H]thymidine assays, remained unaffected in HUVECs after exposure to T3. These data indicate thyroid hormone-induced upregulation of mRNA expression and protein synthesis of vWF, FN and ET-1, by PKC alpha-, beta II- and epsilon-independent pathways, explaining, at least in part, increased plasma concentrations of endothelial proteins and peptides in the hyperthyroid state.

Blotting, Northern↗

PubMed1997

Elevated islet amyloid pancreatic polypeptide and proinsulin in lean gestational diabetes.

Recent research indicates that islet amyloid pancreatic polypeptide (IAPP) might have a regulatory effect on beta-cell insulin processing and secretion. To study such interaction in more detail, IAPP secretion and kinetics and the serum concentrations of proinsulin were assessed both before and after delivery in lean pregnant women with gestational diabetes mellitus (GDM patients) in comparison to those with normal glucose tolerance (NGT) and to nonpregnant healthy lean (control) and obese insulin-resistant women during oral glucose tolerance tests. Kinetic analysis of IAPP was performed with mathematical modeling, providing indirect estimates of its secretion and fractional clearance. Total insulin secretion per 180 min was elevated by 30% in GDM patients (35 +/- 3 pmol/l) versus control subjects (27 +/- 1 pmol/l) (P < 0.05), but increased even more (190-250%) in obese insulin-resistant women, compared with all other groups (68 +/- 7 pmol/l, P < 0.0005). Pregnancy induced a more marked fourfold increase in apparent total IAPP secretion rate (TIR) (GDM patients, 172 +/- 31 pmol x 1(-1) x 3 h(-1); NGT subjects, 166 +/- 31 pmol x 1(-1) x 3 h(-1); control subjects, 40 +/- 1 pmol 1(-1) x 3 h(-1)) and a twofold rise in its fractional clearance versus control subjects (P < 0.01), whereas in GDM patients a 30% increase of IAPP secretion and a decreased clearance was found, compared with obese insulin-resistant women (TIR, 112 +/- 14 pmol x 1(-1) x 3 h(-1)). The increase in IAPP secretion in both pregnant groups was much higher than that of the insulin groups, resulting in a marked change of the IAPP-insulin cosecretion factor when compared with lean or obese nonpregnant women (P < 0.0005). Associated serum proinsulin and the postprandial (total divided by 180 min) proinsulin-to-insulin ratio were greater in GDM patients versus NGT and control subjects (0.11 +/- 0.01 vs. 0.07 +/- 0.01 and 0.08 +/- 0.01 pmol/l, P < 0.05), while the fasting proinsulin-to-insulin ratio was only increased in GDM patients versus control subjects (0.22 +/- 0.03 vs. 0.13 +/- 0.01 pmol/l, P < 0.05). After delivery, total IAPP secretion (52.4 +/- 1.5 pmol/l) was completely normalized in the GDM group, as were the clearance rate and the IAPP-insulin cosecretion factor. Similarly, serum proinsulin concentrations returned to normal, whereas proinsulin-to-insulin ratios remained elevated. In conclusion, IAPP hypersecretion is characteristic for pregnancy and might partially decrease hyperinsulinemia in pregnancy by inhibiting insulin secretion. Increased proinsulin concentrations and a raised proinsulin-to-insulin ratio, which did not abate following delivery, are specific to GDM and might thus serve as its marker and potentially even identify subjects at high risk for the development of NIDDM.

Adult↗

PubMed1996

Insulin-like vs. non-insulin-like stimulation of glucose metabolism by vanadium, tungsten, and selenium compounds in rat muscle.

The direct impact of vanadate, tungstate, selenate, and selenite on glucose metabolism of isolated rat soleus muscle was investigated. All compounds stimulated glucose transport, but only vanadate exerted an insulin-like effect on glycogen synthesis (mumol glucose into glycogen*g-1*h-1: control 1.43 +/- 0.11 vs. 1 mmol/l vanadate, 2.08 +/- 0.11, p < 0.0001), which was more distinct in the presence of 1 mmol/l H2O2 (control, 1.44 +/- 0.13 vs. 1 mmol/l vanadate, 3.49 +/- 0.12, p < 0.001). Glucose handling of muscles exposed to tungstate, selenate, or selenite resembled that of hypoxic muscle, i.e. the induced rise in glucose uptake was inhibited by dantrolene and associated with high rates of glycolysis and rapid glycogen depletion (glycogen content after incubation, mumol glucosyl units/g: control, 16.2 +/- 0.7 vs. hypoxia, 2.7 +/- 0.5, p < 0.0001; control, 17.0 +/- 0.5 vs. 100 mmol/l tungstate, 5.5 +/- 0.4, p < 0.001; control, 16.2 +/- 0.7 vs. 100 mmol/l selenate, 1.5 +/- 0.3, and vs. 300 mumol/l selenite, 1.7 +/- 0.3, p < 0.0001 each). The results suggest that vanadate (and more pronounced it's peroxides) exerts true insulin-like action on isolated muscle glucose metabolism, whereas tungsten and selenium salts trigger glucose transport in association with a catabolic response, which may represent an unspecific response to toxic/osmotic stress.

Androstadienes↗

PubMed1996

Fish oil supplementation versus gemfibrozil treatment in hyperlipidemic NIDDM. A randomized crossover study.

To compare the impact of dietary fish oil supplementation (FO, 22 ml daily, containing 4.6 g of n-3 (omega-3) fatty acids, equalling 14.4 mmol) on carbohydrate and lipid metabolism with that of conventional lipostatic therapy (Gemfibrozil (G), 900 mg daily, equalling 3.6 mmol) on hyperlipidemic non-insulin dependent diabetes mellitus (NIDDM), 10 patients were selected for a randomized, short-time, cross-over study. Each patient was treated for a duration of 2 weeks, with an individual washout period of 8 weeks. Metabolic variables and intravenous glucose tolerances (1.2 mmol/kg body weight, t = 30 min) were determined on days 1 and 15 of each treatment period. Plasma lipid concentrations were identical at baseline, but were reduced more markedly following G as against FO exposure (% change vs. baseline: total cholesterol (chol), - 13**/-6* (G vs FO: p = 0.05); total triglycerides (TG), -39**/-18** (p < 0.05); APO B, -17**/- 10* (N.S.); LDL-chol, -15**/0 (p < 0.02); VLDL-chol, -50***/- 34*** (N.S.); VLDL-TG, -44***/-27** (N.S.); (p vs. baseline: * < 0.05, ** < 0.01, *** < 0.001). Total-HDL, HDL2, HDL3 and APO A were not influenced by either FO or G. Neither FO nor G induced a change in intravenous glucose tolerances or associated basal and incremental concentrations of insulin and C-peptide. We concluded, based on short-time applications, that (a) neither treatment affected the carbohydrate metabolism in patients with NIDDM, and (b) a greater hypolipidemic efficacy had to be assigned to Gemfibrozil than to fish oil. It would therefore appear that Gemfibrozil acts as a useful lipostatic pharmacologic compound, whilst fish oil could serve as a potential ingredient of a prudent cardio-protective diet which favours the low plasma triglyceride concentrations found in NIDDM patients.

Aged↗

PubMed1996

No effect of short-term dietary supplementation of saturated and poly- and monounsaturated fatty acids on insulin secretion and sensitivity in healthy men.

To evaluate the short-term influence of fatty acids with different grades of saturation on insulin secretion and sensitivity, 8 healthy males (age 26 +/- 3.5 years, body mass index 22.4 +/- 1.8 kg/m2) were provided with 800 kcal daily of either carbohydrates (CH; 200 g), or fat (90 g) enriched either with saturated fatty acids (SAFA; 72%) or (omega-6) polyunsaturated fatty acids (PUFA; 60%) or cis-monounsaturated fatty acids (MUFA; 40%; n = 5) in addition to a standard diet (2,000 kcal/ day; 50% CH, 15% protein, and 35% fat; 33% SAFA, MUFA, and PUFA each) for 1 week in a randomized order (washout period 2 weeks). The stimulated insulin secretion was quantified by the frequently sampled intravenous glucose tolerance test (FSIGT; 0.3 g glucose/kg body weight), while the insulin sensitivity was determined by an euglycemic-hyperinsulinemic 5-mU clamp. In parallel, basal and stimulated carbohydrate and fat oxidation rates were estimated by indirect calorimetry. One week of defined fat exposure failed to significantly affect the glucose-induced insulin secretion during FSIGT and insulin-dependent glucose disposal during an euglycemic clamp (M values: CH 9.6 +/- 1.6 mg/kg.min, SAFA 9.7 +/- 2.2, PUFA 9.8 +/- 2.5, and MUFA 11.5 +/- 3.2 mg/kg.min; NS). In addition, oxidation rates for fat and glucose in the postabsorptive state and during hyperinsulinemia did not differ between the different diets. We conclude that short-term (1-week) isocaloric supplementation of a standard diet with fatty acids of varying degree of saturation does not affect either insulin secretion or insulin sensitivity in healthy men, due to the compensatory metabolic capacity of healthy subjects.

Adult↗

PubMed1995

Kinetics of plasma cyclic GMP and atrial natriuretic peptide after intravenous, intramuscular and subcutaneous injection of 50 micrograms hANP in man.

Plasma kinetics of immunoreactive natriuretic peptide (IR-ANP) and cyclic guanosine monophosphate (cGMP) were studied after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) application of 50 micrograms human ANP (hANP) in six healthy, male volunteers. The study was single blind. Mean base-line IR-ANP value (N = 54) was 10.8 +/- 1.8 pmol/l. Five min after injection peak IR-ANP concentrations were reached i.v.: 149.5 +/- 94, i.m.: 25.6 +/- 10.8 and s.c.: 18.3 +/- 3.3 pmol/l while cGMP levels reached maximum values at 15 min or 30 min after application: i.v.: 30.6 +/- 12.1, i.m.: 19.2 +/- 8.5 and s.c.: 17.3 +/- 12.3 nmol/l with a mean base-line value of 13.2 +/- 2.1 nmol/l. The calculated corresponding areas under the IR-ANP curves (AUC) achieved about 22% bioavailability for i.m. and s.c. in comparison with the i.v. application. cGMP bioavailability was about 32%. No statistical difference was calculated between i.m. and s.c. application of 50 micrograms hANP. Changes in IR-ANP levels after i.m. and s.c. administration were not accompanied with effects on urine and electrolyte excretion while there was only a tendency in urine volume and sodium increase after i.v. administration. In conclusion after i.m. or s.c. application of hANP only a minor fraction (approximately 1/5) of IR-ANP is available in circulation in comparison with i.v. application with little or no biological effects.

Adult↗

PubMed1995

Effect of endothelin-1 in man: impact on basal and adrenocorticotropin-stimulated concentrations of aldosterone.

The effect of exogenous endothelin-1 [2 pmol (5 ng)/kg.min for 15 min, followed by 1 pmol (2.5 ng)/kg.min for 105 min] on basal and ACTH (250 micrograms, i.v.)-stimulated plasma concentrations of aldosterone, cortisol, testosterone, corticosterone, and 18-hydroxycorticosterone was investigated in a group of healthy male volunteers (n = 6). Plasma concentrations of aldosterone remained unchanged during a placebo experiment (i.e. in the absence of both exogenous ACTH and of endothelin-1). In the absence of exogenous ACTH, the i.v. administration of endothelin-1 did not influence plasma concentrations of aldosterone. The i.v. administration of 0.25 mg ACTH induced a rise in plasma concentrations of aldosterone from a basal value of 152.6 +/- 38.8 to 362.6 +/- 77.7 pmol/L. This ACTH-induced rise was markedly augmented (P < 0.01) by the concomitant administration of endothelin-1, when peak plasma concentrations of aldosterone of 632.5 +/- 230.2 pmol/L were observed. Basal and ACTH-stimulated concentrations of cortisol, corticosterone, and 18-hydroxycorticosterone were unchanged by the concomitant infusion of endothelin-1. Thus, exogenous endothelin-1 influences adrenal function in healthy men by selectively augmenting the ACTH-induced secretion of aldosterone.

Adrenocorticotropic Hormone↗

PubMed1994

Insulin production following intravenous glucose, arginine, and valine: different pattern in patients with impaired glucose tolerance and non-insulin-dependent diabetes mellitus.

To better understand abnormal insulin production (IP) in states of carbohydrate intolerance, insulin release was quantified following equimolar (2.4 mmol/kg) infusions of glucose, arginine, and valine in healthy subjects ([HS] age, 45 +/- 3 years; body mass index [BMI, kg/m2], 26.3 +/- 2.4; means +/- SEM), obese subjects with impaired glucose tolerance ([IGT] age, 43 +/- 5 years; BMI, 35.4 +/- 2.4), and non-obese patients with chronic non-insulin-dependent diabetes mellitus ([NIDDM] age, 55 +/- 3 years; BMI, 26.4 +/- 1.4; duration of disease, 13 +/- 3 years). There were eight subjects per group. Incremental IP (metabolic clearance rate of C-peptide [MCRCP] x total incremental area under the curve of plasma C-peptide [AUCCP], pmol/kg) following substrate infusion was as follows: glucose: HS, 227 +/- 14; IGT, 1,050 +/- 184 (P < .001 v HS); NIDDM, 114 +/- 27 (P < .001 v HS); arginine: HS, 139 +/- 23; IGT, 488 +/- 106 (P < .01 v HS); NIDDM, 206 +/- 47; and valine: HS, 21 +/- 7; IGT, 32 +/- 10; NIDDM, 54 +/- 12 (P < .01 v HS). The fractional clearance rate ([FCR] k, %/min) was impaired in IGT and NIDDM for glucose (HS, 3.9 +/- 0.4; IGT, 2.3 +/- 0.3 [P < .01 v HS]; NIDDM, 1.4 +/- 0.1 [P < .001 v HS]), arginine (2.4 +/- 0.1; 1.9 +/- 0.2 [P < .01 v HS]; 1.9 +/- 0.2 [P < .01 v HS]), and valine (0.95 +/- 0.06; 0.65 +/- 0.09 [P < .05 v HS]; 0.74 +/- 0.1 [P < .05 v HS]).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Direct shape determination of ribosomal proteins in solution and within the ribosome by means of neutron scattering.

Following the 'strategy of the glassy ribosome' single protonated ribosomal proteins (r-proteins) were reconstituted into deuterated 50S subunits of Escherichia coli. The deuteration of both rRNA and r-proteins were individually adjusted to such a degree that the ribosomal matrix appeared nearly homogeneous with respect to coherent neutron scattering and had a scattering density equivalent to a D2O solution of about 90%. Neutron scattering of ribosomal subunits was recorded in reconstitution buffer containing three different concentrations of D2O around 90% D2O (contrast variation). The signal-to-noise ratio achieved allowed us to make a direct determination of the radii of gyration of r-proteins within the 50S subunit and thus provides the first information relating to the shape of these proteins in situ. We present the radii of gyration of 11 r-proteins incorporated into 50S subunits and of 9 isolated r-proteins in solution. In addition, the data concerning the overall dimensions of the r-proteins we report on indicate that conformational changes of at least two individual r-proteins occur during the assembly process of the ribosome.

Escherichia coli↗

PubMed1994

Islet amyloid polypeptide inhibits insulin secretion in conscious rats.

To investigate the effect of islet amyloid polypeptide (IAPP, amylin) exposure on insulin secretion in vivo, the plasma glucose level of conscious rats was clamped at 11.1 mmol/l (hyperglycemic clamp) during the last 2 h of a 24-h infusion study. Group parameters were A, 24-h saline; B and C, 22-h saline followed by 2-h IAPP (B, 8.5 pmol/min; C, 85 pmol/min), and D, 24-h IAPP (85 pmol/min). Induced hyperglycemia increased plasma insulin concentration by 426 +/- 34 pmol/l in control rats (group A). This effect on plasma insulin was reduced by 31% and 53% during short-term IAPP infusion (group B, 8.5 pmol/min, 294 +/- 41 pmol/l; C, 85 pmol/min, 202 +/- 25 pmol/l; short-term effect, P < 0.0001), whereas insulin levels tended to increase after 24 h of continuous IAPP exposure (group D, 682 +/- 120 pmol/l; P < 0.05 vs. group A). Glucose infusion rate required to maintain constant hyperglycemia fell dose dependently during short-term but not during long-term IAPP infusion (mumol.kg-1.min-1: group A, 203 +/- 11; B, 154 +/- 7; C, 119 +/- 7; D, 212 +/- 9; short-term effect, P < 0.0001). In parallel, muscle glycogen content was dose dependently reduced by short-term IAPP exposure. We conclude that IAPP inhibits glucose-stimulated insulin secretion and decreases muscle glycogen storage in conscious rats in vivo.

Amyloid↗

PubMed1994

Insulin-like growth factor-I inhibits insulin and amylin secretion in conscious rats.

Human recombinant insulin-like growth factor-I (IGF-I) exerts insulin-like antidiabetic properties in vitro and in vivo. To determine the effects of IGF-I infusion on insulin and amylin release, plasma glucose of freely moving undisturbed rats was constantly maintained at 13.9 mmol/liter by variable glucose infusion for 120 min in three groups of fasted Sprague-Dawley rats (hyperglycemic clamp technique). Group A, vehicle infusion (control group); group B, bolus 0.39 nmol plus 0.39 nmol/h IGF-I continously; and group C, bolus 1.96 nmol plus 1.96 nmol/h IGF-I continuously. During the steady-state phase of the experiment, IGF-I dose dependently reduced plasma insulin (pmol/liter: A, 718 +/- 58; B, 613 +/- 35, NS vs. A; C, 408 +/- 21, P < 0.01 vs. A; dose-response effect: P < 0.0001), plasma amylin (pmol/liter: A, 10.2 +/- 0.6; B, 8.8 +/- 0.5, NS vs. A; C, 5.8 +/- 0.4, P < 0.01 vs. A; dose-response effect: P < 0.0001), and net glucose uptake (mumol/kg.min: A, 188 +/- 12; B, 160 +/- 12, NS vs. A; C, 134 +/- 7, P < 0.01 vs. A; dose-response effect: P < 0.0025). At the same time, the ratio of plasma insulin/plasma amylin (mol/mol: A, 72 +/- 6; B, 71 +/- 5; C, 74 +/- 9; NS), the ratio of net glucose uptake/plasma insulin (mumol/kg.min per pmol/liter: A, 0.28 +/- 0.03; B, 0.27 +/- 0.02; C, 0.36 +/- 0.04; NS), and glycogen content of liver, heart, and various hindlimb muscles remained unaffected. The results demonstrate that IGF-I is a potent inhibitor of insulin and amylin release in healthy rats exposed to hyperglycemia and suggest that IGF-I infusion inhibits hormone secretion from pancreatic beta cells at infusion rates that do not affect insulin-stimulated glucose uptake by peripheral tissues.

Amyloid↗

PubMed1994

Stimulation of endothelin-1 production by thrombin, but lack of interference by high ambient glucose in vitro.

Diabetic vascular disease is associated with a state of hypercoagulability and altered endothelial properties, leading to elevated plasma levels of endothelium-derived peptides and proteins, e.g. endothelin-1, von Willebrand factor or fibronectin. This study determined dynamic immunoreactive endothelin-1 secretion by human umbilical vein endothelial cells exposed to thrombin (5 x 10(6) mU/l) in the presence (40 mmol/l) and absence (5.5 mmol/l) of excessive glucose in the cell culture medium. Exposure to high glucose and thrombin concentrations was initiated after cell confluency and applied for 24 h for measurements of endothelin-1 and for 2 and 5 h for the determination of preproendothelin-1, von Willebrand factor and fibronectin messenger ribonucleic acid. Comparisons were made versus cells incubated with normal glucose concentrations or with high mannose or NaCl concentrations as osmotic control. Neither preproendothelin-1, fibronectin and von Willebrand factor messenger ribonucleic acid expression nor endothelin-1 release was affected by high concentrations of glucose, mannose or sodium chloride.

Cells, Cultured↗

PubMed1993

Both acute and chronic near-normoglycaemia are required to improve insulin resistance in type 1 (insulin-dependent) diabetes mellitus.

To determine the impact of both short- and long-term "near-normoglycaemia" on insulin resistance in Type 1 (insulin-dependent) diabetes hepatic glucose production (mg.kg-1.min-1) and peripheral glucose utilisation ("M-value", mg.kg-1.min-1) were estimated during an euglycaemic hyperinsulinaemic clamp (10 mU.kg.min) in patients with either good (HbA1c < 5.8%, groups A and B) or poor (HbA1c > 7.5%, groups C and D) long-term metabolic control (time > 12 months) and in healthy subjects (HbA1c: 5.08 +/- 0.20%; n = 8). To this end blood glucose was stabilized at 6.7 mmol/l by overnight (t = 12 h) i.v. regular insulin in groups (n = 8 each) A (HbA1c: 5.49 +/- 0.46%) and C (HbA1c: 8.83 +/- 1.20%), while groups B (HbA1c: 5.55 +/- 0.19%) and D (HbA1c: 8.51 +/- 1.09%) were kept overnight on long-acting insulin without feed-back control of blood glucose before euglycaemic clamping. Thereby, pre-equilibration of blood glucose at 6.7 mmol/l was shown to normalize basal hepatic glucose production (A: 2.27 +/- 0.48; C 2.50 +/- 0.57 mg.kg-1.min-1) despite different HbA1c values, whereas basal hepatic glucose production stayed elevated in groups B (3.09 +/- 0.38 mg.kg-1.min-1) and D (3.21 +/- 0.58 mg.kg-1.min-1) with poor actual glycaemia (B: 10.9 +/- 4.6; D: 12.1 +/- 4.6 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Non-insulin-like action of sodium orthovanadate in the isolated perfused liver of fed, non-diabetic rats.

Vanadium compounds exert insulin-like effects on isolated rat adipocytes and skeletal muscle and improve glucose homeostasis in diabetic rats and mice. However, reports on metabolic actions of vanadium in the liver are still contradictory. Thus, the acute effect of sodium orthovanadate infusion on net glucose production was measured in isolated perfused livers of non-fasting, non-diabetic rats. Continuous infusion (0.2 ml/min; 90 min) of vanadate (10-500 mumol/l) rapidly increased hepatic glucose (p < 0.001), but not cyclic AMP output, reaching peak values after 20 min. The cumulative glucose release displayed concentration dependence with a maximal net effect of 394.3 mumol/100 g body weight and an apparent half-maximal effective vanadate concentration of 19.6 mumol/l. The glycogenolytic response to vanadate was almost completely blocked by 100 mU/l insulin (p < 0.005), by 0.1 mmol/l indomethacin (p < 0.05) and in the absence of Ca2+ (p < 0.001). These results indicate that sodium orthovanadate stimulates glycogenolysis in livers of fed, non-diabetic rats by a Ca(2+)-dependent mechanism, which may involve the release of prostaglandins.

Animals↗

PubMed1993

Effect of endothelin-1 in man--impact on basal and stimulated concentrations of luteinizing hormone, follicle-stimulating hormone, thyrotropin, growth hormone, corticotropin, and prolactin.

The effect of endothelin-1 on basal and stimulated serum (plasma) concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin (TSH), prolactin (PRL), growth hormone (GH), and corticotropin was investigated in healthy male volunteers (n = 5). Intravenous (IV) administration of endothelin-1 (5 ng/kg/min for 15 minutes, followed by 2.5 ng/kg/min for 105 minutes) induced an increase in basal plasma concentrations of corticotropin. Serum concentrations of PRL, TSH, LH, FSH, and GH remained unchanged. The increase in serum concentrations of these pituitary hormones induced by IV administration of LH-releasing hormone ([LH-RH] 100 micrograms), thyrotropin RH ([TRH] 400 micrograms), GH-RH (100 micrograms), and corticotropin-releasing factor ([CRF] 100 micrograms) was suppressed in regard to PRL (P < .01) and GH (P < .01) and enhanced in regard to corticotropin (P < .01). Stimulated serum concentrations of LH and FSH also tended to be higher following administration of endothelin-1 (P < .05), whereas the increase in serum concentrations of TSH remained unchanged. Thus, when administered in pharmacological doses, endothelin-1 influences pituitary hormone secretion in man.

Adrenocorticotropic Hormone↗

PubMed1993

Dissociation of hemodynamic and renal effects of i.v. alpha-hANF (99-126) in conscious calves.

The effects of i.v. human atrial natriuretic factor (alpha-hANF [99-126]) was investigated in 5 conscious calves (age 4 months, weight 94 +/- 14kg) with constant fluid (300 ml/h) and sodium intake over a period of 24 hours before and during the 3 hours of experimentation. We administered 200 micrograms, 400 micrograms and 800 micrograms ANF at hourly intervals. Immediately (+2 min) after the i.v. injection the peptide's serum-concentration rose from, basal 13 +/- 3 to 802 +/- 191 (200 micrograms), 1707 +/- 419 (400 micrograms) and 3483 +/- 878 pmol/l (800 micrograms) (p < 0.0001), respectively. Mean arterial pressure decreased from, basal, 108 +/- 18 to 85 +/- 17, 76 +/- 16 and 69 +/- 18 mmHg (p < 0.0001), and central venous pressure decreased from, basal, 5.1 +/- 3 to 1.2 +/- 1, 0.4 +/- 1 and 0.8 +/- 2 mmHg (p < 0.001). Heart rate increased from, basal, 66 +/- 5 to 84 +/- 23, 111 +/- 29 and 114 +/- 13 b/min (p < 0.001). Following the administration of ANF the urine volume decreased from, basal, 261 +/- 145 to 195 +/- 72, 121 +/- 41 and 102 +/- 33 ml/h (p < 0.0041). The urinary sodium excretion rates decreased from, basal, 50 +/- 17 to 30 +/- 13, 22 +/- 10 and 19 +/- 10 mmol/h (p < 0.007), and the potassium excretion rates decreased from, basal, 43 +/- 19 to 39 +/- 16, 26 +/- 11 and 23 +/- 10 mmol/h (p < 0.0047). Endogenous clearance of creatinine (basal: 182 +/- 30 ml/min) did not change (260 +/- 84, 218 +/- 66 and 224 +/- 76 ml/h) following i.v. ANF. Inspite of this marked fluid retention, the hematocrit, expressed as relative change, was increased by 7.5%, 11.8% and 10.4%. In 2 calves we additionally measured an increased whole blood and plasma density possibly indicating increased liquid permeation to an extravascular compartment. Thus, in calves the hemodynamic effects of ANF are comparable to those seen in man. However, the failure of ANF to stimulate diuresis and natriuresis indicates a dissociation of hemodynamic and renal effects of ANF in calves.

Animals↗

PubMed1993

PCR buffer optimization with uniform temperature regimen to facilitate automation.

To facilitate PCR(1,2) reactions in large numbers with uniform conditions, the annealing temperature was fixed and the stringency of the reactions was adjusted by optimizing the ion conditions of the reaction. The buffer system is based primarily on Tris (T), ammonium (N), and potassium (K) to adapt assay conditions to different primer pairs. The TNK buffers have permitted successful screening of a 60,000-clone yeast artificial chromosome (YAC) library with more than 200 primer pairs.

Automation↗

PubMed1993

Insulin resistance caused by amylin in conscious rats is independent of induced hypocalcemia and fades during long-term exposure.

To compare the effect of short- vs long-term amylin infusion on insulin sensitivity, glucose tolerance and serum calcemia, euglycemic-hyperinsulinemic clamp (26 pmol.kg-1 x min-1) and glucose tolerance tests (2.4 mmol/kg over 30 min) were performed in lean Zucker rats. Three infusion protocols were employed: control group: 24 h of i.v. saline; short-term amylin exposure: 22 h of i.v. saline followed by 2 h of i.v. amylin (20 micrograms/h); long-term amylin exposure: 24 h of iv amylin (20 micrograms/h). Insulin resistance was induced by short-term amylin infusion during euglycemic clamping, as shown by a 41% decrease in space-corrected glucose infusion rates (mumol.kg-1 x min-1; control group, 106.0 +/- 15.0; short-term i.v. amylin, 62.7 +/- 15.0; p < 0.005). After long-term amylin exposure, insulin sensitivity was identical to control values (109.9 +/- 6.7). This fading action of amylin was confirmed by data from the glucose tolerance test, demonstrating glucose intolerance after short- but not after long-term amylin exposure. Serum calcium concentration decreased during short-term (2 h) amylin infusion (from 2.52 +/- 0.15 to 2.09 +/- 0.12 mmol/l; p < 0.01) and hypocalcemia of a similar extent also was present after 22 h and 24 h of amylin exposure (2.10 +/- 0.09 and 2.04 +/- 0.14 mmol/l, respectively). The data demonstrate that short-term amylin infusion induces insulin resistance and glucose intolerance, both of which vanish during long-term (> 22 h) amylin exposure, being apparently independent of induced hypocalcemia.

Amyloid↗