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Biomedical subjects

W Kemmler

Publications and source records attributed to W Kemmler.

At least 19 recordsLinked to original sources
PubMed1984

Extrapancreatic action of the sulphonylurea gliquidone: post-receptor effect on insulin-stimulated glycogen synthesis in rat hepatocytes in primary culture.

The effects of a sulphonylurea, gliquidone, on insulin binding and the insulin induced rate of glycogen synthesis, were studied in rat hepatocytes in primary culture. Hepatocytes were cultured for 48 h. During the second 24 h of this period, the hepatocytes were incubated with or without gliquidone (5 mg/l). The binding of 125I-insulin and the insulin stimulation of glycogen synthesis from 14C-glucose were measured. Gliquidone influenced neither insulin binding nor the basal rate of glycogen synthesis, but it did enhance the effect of insulin on glycogen synthesis. Responsiveness was increased by gliquidone at all insulin concentrations used (10-10,000 mU/l); at 1000 mU/l the drug increased glycogen synthesis from 310 to 430% above the basal rate. Half-maximal stimulation was reached in control cells at an insulin concentration of 95 mU/l and in gliquidone-treated cells at 94 mU/l, which indicates unchanged insulin sensitivity. Based on these experiments with cultured rat hepatocytes it appears that the extrapancreatic action of gliquidone is not mediated by an effect on insulin binding.

Animals↗
PubMed1983

Catecholamine-induced insulin resistance of glucose transport in isolated rat adipocytes.

The effects of pre-incubation with isoprenaline and noradrenaline on insulin binding and insulin stimulation of D-glucose transport in isolated rat adipocytes are reported. (1) Pre-incubation of the cells with isoprenaline (0.1-10 microM) in Krebs-Ringer-Hepes [4-(2-hydroxyethyl)-1-piperazine-ethanesulphonic acid] buffer (30 min, 37 degrees C) at D-glucose concentrations of 16 mM, in which normal ATP levels were maintained, caused a rightward-shift in sensitivity of D-glucose transport to insulin stimulation by 50% and a decrease in maximal responsiveness by 30% (2) [A14-125I]insulin binding was reduced significantly by 35% at insulin concentrations less than 100 mu-units/ml and Scatchard analysis showed that this consisted mainly of a decrease in high-affinity binding. (3) Pre-incubation with catecholamines under the same conditions but at low glucose concentrations (0-5 mM) caused a fall in intracellular ATP levels of 65 and 45% respectively. (4) The fall in ATP additionally lowered insulin binding by 50% at all insulin concentrations and a parallel shift of the binding curves in the Scatchard plot showed that this was due to a decrease in the number of receptors. (5) At low and high ATP concentrations the insulin stimulation of D-glucose transport was inhibited to a similar extent. (6) Pre-incubation with catecholamines thus inhibited insulin stimulation of D-glucose transport in rat adipocytes mainly by a decrease in high-affinity binding of insulin, which was not mediated by low ATP levels. This mechanism may play a role in the pathogenesis of catecholamine-induced insulin resistance in vivo.

Adenosine Triphosphate↗
PubMed1983

Cyclic AMP modulates insulin binding and induces post-receptor insulin resistance of glucose transport in isolated rat adipocytes.

The effect of cAMP on insulin binding and insulin stimulation of glucose transport was investigated in isolated rat adipocytes. Preincubation for 30 min in medium containing 16 mmol/l glucose and either db-cAMP or bromo-cAMP in concentrations of 10(-4)-10(-3) M inhibited high affinity binding of insulin by 15 to 30% and glucose transport by 30 to 50%. Preincubation with IBMX (10(-4)-10(-3) M) reduced insulin binding by 25% and glucose transport by 70%. Closer analysis of these data indicated that preincubation with these compounds caused not only a decrease in insulin binding but also a post-receptor resistance. High intracellular cyclic AMP-levels seem therefore to induce insulin resistance at both receptor and post-receptor levels.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Insulin binding and action in antibody-induced diabetes in the rat.

The influence of antibody-induced insulin deficiency in rats on the insulin binding and insulin sensitivity of adipocytes was studied. Rats were injected intraperitoneally with an insulin antibody preparation; the development of hyperglycaemia was followed and the animals were sacrificed 3 and 5 h after antibody injection. Up to 3 h, no significant change of insulin binding or sensitivity of the adipocytes occurred. At 5 h, cells of antibody-treated rats showed an approximately 40% increased binding capacity compared with untreated rats. The increased binding capacity was accompanied by an approximate two-fold increased sensitivity of the insulin effect on lipogenesis from glucose in these cells.

Adipose Tissue↗
PubMed1982

Relation of insulin receptor occupancy and deactivation of glucose transport.

Kinetics of association and dissociation of 125I-insulin and of activation and deactivation of 3-O-methylglucose transport were determined in isolated rat fat cells. Equilibrium bound insulin (7.5, 25, 100 microunits/ml) dissociated with a t1/2 of 2 min (100 microunits/ml), 4 min (25 microunits/ml), and 16 min (7.5 microunits/ml). Consecutive deactivation of transport is observed only in the presence of glucose (1 mM); the t1/2 of deactivation is approximately 60 min (100 and 25 microunits/ml) and 20 min (7.5 microunits/ml). At 15 degrees C, the t1/2 of dissociation (7.5 microunits/ml) is 25 min, and deactivation is not observed. Addition of dithioerythritol (5 mM) during the association of insulin decreased the binding rapidly; however, a reduced insulin effect was only seen if the binding decreased during the early activation phase of transport. In conclusion, the maintenance of the insulin effect on transport does not require persistent receptor occupancy; dissociation and deactivation are, with respect to kinetics, temperature dependency and requirement of glucose, independent processes. Receptor occupancy probably only controls the activation of transport; deactivation seems to be controlled by postreceptor processes.

3-O-Methylglucose↗
PubMed1981

Coupling of insulin binding and insulin action on glucose transport in fat cells.

The initial lag phase of insulin action on glucose transport in adipocytes reflects an unknown process that couples receptor binding and glucose transport activity. The influence of temperature, cellular ATP, cyclic AMP, and calcium on this process and a possible relation to internalization of insulin were studied. The Arrhenius plot of the coupling shows a break in slope at 30 degrees C; the activation energy below 30 degrees C is 17.5 kcal/mol. Reduction of cellular ATP by 70% prolongs the coupling process; initial binding and final maximal response of the glucose transport remain unaffected. Further reduction of ATP (greater than 90%) before addition of insulin abolishes the coupling completely. Reduction of ATP at different time points after addition of insulin blocks further activation; however, the actual state of activity is preserved. Calcium depletion by EDTA prolongs the coupling and decreases the maximal response. Internalization of insulin as determined in chloroquine-treated cells begins later than transport activation and is in contrast to transport activation not observable at 15 degrees C. In conclusion, the coupling is not related to internalization; it is ATP-dependent, whereas the initial binding and the activated transport system are ATP-independent. Calcium but not cyclic AMP might be second messenger or cofactor in the coupling process.

3-O-Methylglucose↗
PubMed1980

Insulin binding and insulin action in rat fat cells after adrenalectomy.

Insulin binding and the effect of insulin on the transport of 3-O-methylglucose, lipogenesis from glucose, glucose oxidation and lipolysis was studied in fat cells of adrenalectomised rats and of a control group of sham-operated rats. The serum insulin level of the adrenalectomised rats (0.7 ng/ml) was lower than that of the controls (1.6 ng/ml). In adrenalectomised rats as compared to sham-operated rats the insulin concentrations causing half-maximal effect were reduced by 50% in lipogenesis and antilipolysis and by 30% in glucose transport. The increase in sensitivity to submaximal insulin concentrations was not observed in glucose oxidation. The maximal responsiveness was unchanged in all test systems. The increase in sensitivity in three of the four studied insulin effects may be related to the 37% increase in the binding capacity of fat cells from adrenalectomised compared with sham-operated rats. The unchanged sensitivity with respect to glucose oxidation indicates possible post-receptor modulation. When adrenalectomised rats were substituted with either insulin or cortisol serum insulin levels were elevated above normal; however, the changes in the receptor were prevented in the cortisol supplemented rats and only partially in the insulin supplemented rats. The observation suggests, that the insulin receptor is regulated not only by the serum insulin level but also by cortisol.

Adipose Tissue↗
PubMed1979

[Effect on carbohydrate metabolism of a new saluretic, etozolin].

The influence of Etozolin (Elkapin) on the carbohydrate metabolism was studied in 10 healthy volunteers, 6 patients with chemical diabetes and 10 with overt diabetes by blood glucose measurements and oral glucose tolerance tests with determinations of serum insulin levels. The healthy volunteers received 800 mg Etozolin per day during the treatment period of 3 days, the two groups of patients 400 mg Etozolin for 8 days. The laboratory parameters of the treatment period were compared with the corresponding values of the pre- and posttreatment periods and evaluated statistically. There was no statistically significant difference in the carbohydrate metabolism between the 3 test periods in all groups studied. As a result of the induced diuresis body weight, serum electrolytes and urine volume changed significantly during the Etozolin treatment as compared with the pre- and posttreatment values. Other changes of laboratory parameters could not be seen. In diabetic hypertensive patients a significant reduction of blood pressure was observed.

Adult↗
PubMed1979

Free insulin, bound insulin, C-peptide and the metabolic control in juvenile onset diabetics: comparison of C-peptide secretors and non-secretors during 24 hours conventional insulin therapy.

In two groups of juvenile onset diabetics similar in age, weight, diet and daily insulin dosage (eight without C-peptide, group I; eight with C-peptide, group II) the serum levels of free and antibody bound insulin, C-peptide, glucose, lactate, alanine and FFA were determined over 24 h. In addition the affinity and binding capacity of the insulin antibodies were determined in vitro. No correlation was found between free or bound insulin and glucose. This holds true for the individual profiles as well as for the averaged profiles of the two groups. Free insulin and lactate or alanine were positively correlated in the C-peptide secreting group. C-peptide secretion followed the flucturations of the glucose level during 24 h in each individual patient. As a group, C-peptide secretors were better controlled than non-secretors with respect to mean blood glucose, M-value and the lability index and showed higher free insulin levels despite a similar daily insulin dosage. The possible reasons for this fact are discussed. No correlation was found between the affinity characteristics of the insulin antibodies and the degree of metabolic control or the daily insulin dosage.

Adolescent↗
PubMed1978

Interactions between insulins and liver membrane receptors of guinea pig, calf and chicken. Exclusion of a species-specific insulin receptor.

Insulin binding experiments were performed with liver plasma membranes from guinea pig, calf and chicken. Bound insulin was separated from free insulin by a simple and rapid centrifugation of membranes through a layer of silicon oil. 125 I-labeled beef insulin was displaced from receptor sites by unlabelled guinea pig, beef and chicken insulin. The receptors of animals with insulins of different biological activity show similar basic characteristics and affinities to the different insulin molecules and thus are not specialised for the interactions with the homologous insulin molecule. The binding capacity of the membranes for beef insulin seems to be inversely related to the affinity of the homologous insulin to the receptor, guinea pig membranes showing the highest and chicken membranes the lowest receptor concentration.

Animals↗
PubMed1977

NaK-ATPase in rat pancreatic islets.

Shifts in the distribution of the monovalent cations Na+ and K+ between the extra- and intracellular space seem to be important for the secretory response of the beta-cell. An attempt was therefore made to study the enzyme responsible for monovalent cation transport, the (NaK)-activated ATPase. In the presence of NaN3 as inhibitor of the mitochondrial Mg-ATPase, a NaK-ATPase with a specific activity of 72 mU X mg protein-1 could be demonstrated in crude membrane preparations of rat pancreatic islets. The enzyme, which was inactive in the absence of Mg++, needed both Na+ and K+ for activation and was inhibited by ouabain and PCMB. The main part of the NaK-ATPase was localized in the microsomal fraction. Glucose, sulphonylureas, somatostatin and diazoxide were without effect on NaK-ATPase.

Adenosine Triphosphatases↗