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H Reinauer

Publications and source records attributed to H Reinauer.

At least 73 records · Page 4Linked to original sources
PubMed1990

G-protein-mediated regulation of the insulin-responsive glucose transporter in isolated cardiac myocytes.

Isolated muscle cells from adult rat heart were used to study the involvement of G-proteins in the regulation of the glucose transporter by insulin and isoprenaline. Efficient modification of G-protein functions was established by measuring isoprenaline-stimulated cyclic AMP production, viability and ATP content after treating the cells with cholera toxin and pertussis toxin for 2 h. Under these conditions cholera toxin decreased the stimulatory action of insulin on 3-O-methylglucose transport by 56%, but pertussis toxin had no effect. Basal transport was not affected by toxin treatment. Isoprenaline increased 3-O-methylglucose transport by 63%. This effect was not mimicked by dibutyryl cyclic AMP, but was completely blocked by cholera toxin. Streptozotocin-diabetes abolished isoprenaline action and decreased stimulation of transport by 64%. Concomitantly, cholera-toxin sensitivity of glucose transport was lost in cells from diabetic animals. This was paralleled by a large decrease (87 +/- 4%) in mRNA expression of the insulin-regulatable glucose transporter, as shown by Northern-blot analysis of RNA isolated from cardiomyocytes of diabetic rats. These data suggest a functional association between the insulin-responsive glucose transporter and a cholera-toxin-sensitive G-protein mediating stimulation by insulin and isoprenaline.

3-O-Methylglucose↗
PubMed1990

Structural requirements for signal transduction of the insulin receptor.

Structural requirements for signal processing by human placental insulin receptors have been examined. Insulin binding has been found to change the physico-chemical properties of (alpha beta)2 receptors solubilized with Triton X-100, indicating a marked alteration of the form, i.e. size and shape, of the molecular complex. (a) The Stokes radius decreases from about 9.5 nm to 7.9 nm, as determined by PAGE with Triton X-100 in the buffer (Triton X-100/PAGE), and from 9.1 nm to 8.7 nm, as assessed by gel filtration. (b) The sedimentation coefficient s20,w rises from 10.1 S to 11.4 S. Upon dissociation of the receptor-hormone complex, the alterations are reversed. After autophosphorylation of hormone-bound (alpha beta)2-insulin receptors, phosphate incorporation was found for 7.9-nm receptor forms when receptor-insulin complexes were crosslinked with disuccinimide suberate prior to Triton X-100/PAGE. However, phosphate incorporation was demonstrated for the 9.5-nm receptor forms when receptor-insulin complexes were not prevented from dissociation. This strongly indicates that the (alpha beta)2 receptor is autophosphorylated after assuming its 7.9-nm form upon insulin binding. Moreover, the insulin-dependent structural alterations are not affected by autophosphorylation. In contrast to (alpha beta)2 receptors, the diffusion and the sedimentation behaviour of alpha beta receptors, which carry a dormant tyrosine kinase even in the hormone-laden state, has been found to be insensitive to insulin binding. Different molecular properties of alpha beta and (alpha beta)2 receptors have also been detected by hormone binding studies. Insulin binding to (alpha beta)2 and alpha beta receptors differs markedly with respect to pH, ionic strength, and temperature. This might indicate that the structure of the hormone binding domain of alpha beta receptor changes on association into the (alpha beta)2 species. Alternatively, distinct hormone-induced conformational alterations at the molecular level of alpha beta and (alpha beta)2 receptor species may lead to the different binding properties. Our data demonstrate that the (alpha beta)2-insulin receptor undergoes extended conformational alterations upon insulin binding. This capacity for structural changes coincides with the hormone-inducable enhancement of tyrosine autophosphorylation of the 7.9-nm insulin-bound receptor form. In contrast, alpha beta receptors appear to be locked in an inactive nonconvertable state. Thus, interaction between two alpha beta receptor units is required to allow extended conformational alterations, which are assumed to be the triggering event for augmented auto-phosphorylation.

Amino Acids↗
PubMed1990

Modulation of transmembrane potential of isolated cardiac myocytes by insulin and isoproterenol.

Isolated muscle cells from adult rat heart have been used to study the effects of insulin and catecholamines on transmembrane potential by following triphenylmethylphosphonium cation uptake. Insulin was found to hyperpolarize the cells with a maximal effect of 3.2 +/- 0.7 mV (n = 4) at an insulin concentration of 3 x 10(-9) mol/l. This insulin action was fully antagonized by isoproterenol (10(-5) mol/l), which depolarized the cardiocytes in a dose-dependent fashion with a maximal effect of 9.5 +/- 2.2 mV. Treatment of cardiocytes with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid or CsCl resulted in a total loss of insulin action, whereas isoproterenol action was not affected. Cardiac myocytes from streptozotocin diabetic rats exhibited an unaltered hyperpolarization by insulin within the physiological concentration range. Isoproterenol now induced a biphasic response with a significant hyperpolarization at low doses and a decreased depolarization at maximal concentrations. In conclusion, 1) hormonal modulation of cardiac myocyte membrane potentials involves hyperpolarization by insulin and depolarization by beta-agonists, 2) insulin action appears to be related to an increased potassium conductance and may be antagonized by beta-stimulation, and 3) membrane potential modulation may be profoundly altered in the diabetic state.

Animals↗
PubMed1990

Determination of glucose turnover and glucose oxidation rates in man with stable isotope tracers.

Determination of the turnover rates of glucose gives a more dynamic view of carbohydrate metabolism. Using 2H- or 13C-labelled glucose, stable isotope methods have been established which are free of risk for volunteers or patients and are in accordance with the legal requirements for radiation protection. The aim of the present study was to determine the main parameters of glucose turnover in vivo by using two stable-isotope-labelled glucose molecules, [6,6-2H]glucose and [U-13C]glucose. Under steady state conditions, the following parameters were analysed: glucose turnover rate, glucose oxidation rate, recycling of glucose, hepatic glucose production rate, and glucose clearance. In healthy volunteers the following data were obtained for the glucose turnover rate: 2.42 +/- 0.11 mg/kg x min, glucose oxidation rate 1.34 +/- 0.08 mg/kg x min, glucose clearance 3.04 +/- 0.17 ml/kg x min, and glucose recycling 24.7% (about 0.6 mg/kg x min). Under conditions of the euglycaemic-hyperinsulinaemic clamp (insulin levels about 80 mU/l) the glucose turnover rate increased to 9-10 mg/kg x min, and the hepatic glucose production rate was totally suppressed. Under these conditions identical glucose turnover rates were measured by rate of appearance Ra and euglycaemic-hyperinsulinaemic clamp. These data clearly demonstrate that by using differentially labelled glucose molecules at least five parameters of glucose metabolism may be determined in vivo. High insulin levels (70-80 mU/l) stimulate glucose turnover rate by 300-400%, and the glucose infusion rate agrees well with the rate of appearance (Ra) of glucose, determined with [6,6-2H]glucose. Thus, this glucose tracer provides relevant and presumably accurate data under basal and under hyperinsulinaemic conditions.

Adult↗
PubMed1990

[Rheologic changes in the postprandial phase].

In this study, the postprandial changes of blood rheology and lipid parameters after a lipid-enriched test meal (75% lipids) versus a normal lipid composition control meal (30% lipids) were monitored. Six healthy volunteers were given a high lipid test meal (85 g lipids, 3800 kJ) as well as a control test meal (30% lipids, 3730 kJ) after 7 days. 3-6 hours after ingestion of the test meal, triglyceride levels peaked with an increase of about 120% after the lipid-enriched test meal and of about 55% after the control meal. The mean levels of plasma viscosity increased from 1.25 mPas to 1.29 mPas 3 hours after ingestion of the lipid-enriched test meal, whereas the blood rheology parameters, such as plasma viscosity and red blood cell aggregation, were nearly unchanged after the control meal with normal lipid composition. The changes of plasma viscosity after the lipid-enriched test meal were caused by an increase of triglyceride levels and an increase of fibrinogen levels in the postprandial phase by nearly 60% (mean value). Two different rheological reaction patterns have been demonstrated. Whereas 5 individuals showed the increase of blood rheology parameters mentioned above, one person had a very pronounced increase of plasma viscosity from 1.34 to 1.42 mPas and fibrinogen levels from 155 mg/dl to 280 mg/dl after the lipid-enriched test meal. This marked postprandial increase of blood viscosity may contribute to a flow limitation of myocardial microcirculation in patients with coronary artery disease.

Adult↗
PubMed1990

Influence of carnitine acyltransferase inhibitors on the performance and metabolism of rat cardiac muscle.

The effects of carnitine palmitoyl transferase I inhibitors were studied in isolated perfused rat heart and in in vivo studies with normal and diabetic rats. In isolated perfused rat hearts of acutely diabetic and Zucker rats, clomoxir (sodium 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate) inhibited the oxidation rate of endogenous fatty acids and increased the oxidation rate of glucose. Etomoxir, an analogue of clomoxir, was used in the in vivo studies with normal and chronic diabetic rats. Etomoxir (18 mg/kg) was given daily for 6 days by intraperitoneal injection. This carnitine palmitoyl transferase inhibitor significantly ameliorated the decreased heart performance in diabetic rats. The concentrations of glucose, glycerol, triacylglycerol, cholesterol, and phospholipids in serum were lower compared with untreated diabetic animals. On the other hand, the lipid and the carnitine content of heart and liver increased in the etomoxir-treated rats. Carnitine palmitoyl transferase inhibitors have clear antidiabetic effects, but before using as an oral antidiabetic drug, the long-term changes of the lipid and carnitine metabolism should be evaluated.

Acyltransferases↗
PubMed1988

Involvement of hormone processing in insulin-activated glucose transport by isolated cardiac myocytes.

Isolated muscle cells from adult rat heart were used to study the relationship between myocardial insulin processing and insulin action on 3-O-methylglucose transport at 37 degrees C. Internalization of the hormone as measured by determination of the non-dissociable fraction of cell-bound insulin increased linearly up to 10 min, reaching a plateau by 30-60 min at 3 nM-insulin. At this hormone concentration the onset of insulin action was found to be biphasic, with a rapid phase up to 8 min, followed by a much slower phase, reaching maximal insulin action by 30-60 min. Insulin internalization was totally blocked by phenylarsine oxide, whereas dansylcadaverine had no effect on this process. Initial insulin action (5 min) on glucose transport was not affected by chloroquine and dansylcadaverine, but was completely abolished by treatment of cardiocytes with phenylarsine oxide. This drug effect was partly prevented by the presence of 2,3-dimercaptopropanol. Under steady-state conditions (60 min), the stimulatory action of insulin was decreased by about 60% by both chloroquine and dansylcadaverine. This study, demonstrates that insulin action on cardiac glucose transport is mediated by processing of the hormone. The data suggest dual pathways of insulin action involving initial processing of hormone-receptor complexes and lysosomal degradation.

3-O-Methylglucose↗
PubMed1988

Influence of the carnitine palmitoyltransferase inhibitor POCA on myocardial performance and metabolism of insulin resistant rats.

The specific carnitine palmitoyltransferase I (CPT I)-inhibitor POCA - sodium-2(5-(4-chlorphenyl)pentyl-oxirane carboxylate - was used in isolated perfused hearts of acutely diabetic, ketotic (AD, 100 mg streptozotocin/kg body weight), chronically diabetic (CD, 60 mg streptozotocin/kg body weight), and obese ZUCKER rats (fa/fa) to study different forms of insulin resistance. In hearts of AD rats an absolute insulin resistance was observed which could be attenuated by perfusion of the hearts with POCA (10 microM). The insulin sensitivity could be fully restored and was not any longer significantly different from control hearts. In hearts of CD rats, which show a relative insulin resistance, POCA only slightly stimulated glucose oxidation and uptake, but the total rate of uptake and conversion of glucose as well as the responsiveness of these hearts to insulin remained low. In hearts of obese ZUCKER rats, the rate of glucose oxidation was accelerated to control levels by perfusion with POCA, however, the rate of glycolysis and glucose uptake remained reduced as compared to controls. Thus, POCA shifted the glucose metabolism by stimulating oxidation without normalizing the reduced glucose uptake. It follows that in hearts of AD rats the insulin resistance is due to the accelerated lipid metabolism described and is, therefore, fully reversible if the oxidation of fatty acids is inhibited. In hearts of ZUCKER rats a form of insulin resistance mediated by lipid metabolism seems to be responsible for the reduced glucose oxidation and the lowered rate of glycolysis. The insulin resistance can be eliminated and has to be distinguished from a defect in the glucose uptake system not affected by POCA. In hearts of CD rats insulin resistance is not dependent on disturbances in lipid metabolism and is practically not influenced by POCA. Thus, a CPI I-inhibitor might be useful to differentiate various forms of insulin resistance and therapeutically beneficial in forms mediated by lipid metabolic defects.

Animals↗
PubMed1987

Insulin binding to erythrocytes in hyperinsulinemic patients with precirrhotic hemochromatosis and cirrhosis.

This study investigated insulin receptor binding (number and affinity) to erythrocytes in patients with precirrhotic hemochromatosis, patients with cirrhosis, and healthy subjects. To evaluate plasma glucose and insulin levels, an oral glucose tolerance test (OGTT) was performed in all subjects. In the fasting state, all patients exhibited normal glucose levels. Precirrhotic patients showed slight impairment of glucose tolerance while cirrhotic patients were strikingly glucose intolerant. In both patient groups, fasting plasma insulin levels were increased. Following the glucose load, plasma insulin levels were significantly enhanced in precirrhotic patients at 90 and 120 min and increased at all times in cirrhotic patients. In the postabsorptive state (in the presence of hyperinsulinemia) insulin binding and the number and affinity of insulin receptors of erythrocytes were not different in precirrhotic or cirrhotic patients when compared to controls. We conclude that studies of insulin binding on erythrocytes do not contribute to the evaluation of the pathogenesis of insulin resistance in liver disease.

Blood Glucose↗
PubMed1987

The contribution of small gut to the 3-methylhistidine metabolism in the adult rat.

Twenty male adult Sprague-Dawley rats received parenteral nutrition following a duodenoileostomy which left only 8% to 10% of the small gut intact. On the first postoperative day, the urinary 3-methylhistidine (3-MH) excretion rose to 1.5 to 1.7 times the preoperative level but fell again within 12 to 14 days to the basal level. A control group of 10 rats with small gut anastomosis without resection yielded similar results. We conclude that, at least in rats, the small intestine does not make a significant contribution to 24-hour urinary excretion of 3-MH. The transient postoperative rise in 3-MH excretion is probably due to postinjury metabolism.

Animals↗
PubMed1987

[Effect of lipid emulsions on nitrogen balance within the scope of perioperative parenteral feeding regimens].

Patients with colorectal cancer were parenterally fed before and after surgery by two different isocaloric regimens: One group was infused with high carbohydrate solutions (carbohydrate group), the other group with carbohydrate in combination with fat emulsions (fat group). The daily dose of fat was restricted to 1 g fat/kg BW/day. These conditions led to the following results: No significant changes in the protein balance were observed between the patients of the two regimens. The protein sparing effect and the synthesis of short living proteins were comparable. The infused fat emulsions were utilized without metabolic complications. Patients in the fat group were adequately supplied with essential fatty acids which was documented by the higher level of linolic acid in the blood. The biochemical and histological analysis of the liver samples which were excised on occasion of surgery gave comparable triglyceride content in both groups. In the fat group little lipid deposition was seen in the parenchymal cells but lipid droplets were observed in the reticuloendothelial system (v. Kupffer cells). Thus, distribution of fat droplets is different in the 2 groups. Unfortunately analysis of lipid depositions in the liver at the end of the parenteral nutrition could not be performed.

Adenocarcinoma↗
PubMed1987

[Limits of the extensive use of glucose as infusion carbohydrate in parenteral nutrition].

The limiting factors for parenteral nutrition with glucose are indicated by the metabolic states of the patients. The rate of glucose utilization is mainly restricted by the degree of insulin resistance which may be localized at the receptor (down regulation, tyrosine kinase?) or at the postreceptor (mediators? Randle-mechanism) level. Usually, clear data about the rate of glucose production in the liver and glucose utilization in the peripheral organs are lacking, and therefore the glucose infusion rate cannot be calculated individually. The glucose infusion rate is usually adapted by monitoring the glucose and insulin levels in the patients; furthermore, insulin-resistant states may be detected by these parameters. As glucose is a main energy source in parenteral nutrition, up to 500 mg glucose/kg B.W./h may be infused in addition to a recommended amount of amino acids and lipid emulsions. Permanent infusion of glucose (over 24 h) is metabolically not adequate, since permanent hyperglycemia and hyperinsulinemia may lead to lipid deposition in the liver. In insulin-resistant states with hyperglycemia glucose infusion rates are limited and should be carefully adapted. Under these circumstances, glucose may be partly replaced by xylitol and sorbitol. Still unanswered is the question of whether the limited glucose utilization rate should be increased by therapeutic interventions. The elimination of insulin-resistant states should be useful in the postaggression syndrome. This therapeutic regimen would also promote protein and lipid synthesis. Since insulin is a main anabolic hormone, its optimal action should be restored as soon as possible.

Blood Glucose↗