Biomedical subjects
K D Hepp
Publications and source records attributed to K D Hepp.
Effect of colchicine and vinblastine on the coupling of insulin binding and insulin action in fat cells.
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[Pre-programmed continuous insulin infusion for the control of diabetes mellitus (author's transl)].
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Substitution of islet-cell function with "open-loop" insulin infusion systems.
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Reduced insulin binding to hepatic plasma membranes in D-galactosamine-treated rats.
Six to 12 hr after IP injection of 400 mg/kg of D-galactosamine in rats a 5-fold increase in plasma insulin was observed. In addition, impaired glucose assimilation was present after an IV Load in spite of unchanged fasting glucose levels. In streptozotocin-diabetic rats (100 mg/kg IV) plasma insulin remained diminished 12 h after induction of D-galactosamine hepatitis. Under identical conditions of preparation and incubation, the liver plasma membranes of D-galactosamine-treated rats, in both normal and diabetic states, bound only 40--60% as much insulin per mg of membrane protein as those of the control rats. Scatchard analysis suggested that this was due to a decrease in the number of receptor sites in the membranes of the D-galactosamine-injected rats. No difference in the insulin degrading capacity and in insulin-receptor dissociation of the plasma membranes between control and D-galactosamine-treated groups was found. These data suggest that a reduction in the number of hepatic insulin receptors in galactosamine hepatitis can lead to insulin resistance and hyperinsulinaemia.
Continuous intravenous insulin therapy with a miniaturized open-loop system.
For the continuous intravenous application of insulin, a portable open-loop system was developed consisting of a delivery unit with a miniaturized pump and an insulin reservoir which is connected with an electronic control unit. The infusion rates were either preprogrammed or patient-controlled. Blood glucose control with both systems was tested in eight juvenile-type diabetics, among them two of the brittle type. Diabetic control during a 1-2-day pre-infusion period was compared with 2-3 days of continuous insulin infusion; as judged by the mean blood glucose value (MBG), the mean amplitude of glycemic excursions (MAGE), and glucosuria, all patients were significantly better controlled by the open-loop systems than by conventional therapy with subcutaneous insulin. The use of portable open-loop systems offers a promising approach to an improvement of metabolic control in insulin-requiring diabetics.
Initial lag-phase in the action of insulin on glucose transport and cAMP levels in fat cells.
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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.
Inhibition of catecholamine-stimulated adenylate cyclase in fat cells by local anaesthetics.
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Preparation and physical-chemical characterization of poly-N-vinylpyrrolidone-insulin.
In an attempt to modify the structure of insulin, the hormone was coupled by covalent linkage to poly-N-vinylpyrrolidone (PVP). PVP-insulin is soluble in aqueous solution and was purified by column chromatography. Special care was taken to check for a possible leakage of insulin from the synthetic polymer. The amount of bound insulin was determined by quantitative amino acid analysis after acid hydrolysis. After protection of the N-terminal glycine residue of the A-chain by citraconylation, a biologically active PVP-insulin was obtained. The molecular weight determined by analytical ultracentrifugation and column chromatography was 50 000-60 000. The biological activity of the coupled hormone was between 0.5 and 7% when compared with native insulin in the system in vitro. The immunological activity was about 20-50%.
[Insulin, glucagon binding and adenylate cyclase activity of liver plasma membranes in streptozotocin-diabetic rats].
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[Psychiatric and neurologic disturbances in thyroid disorders (author's transl)].
The effects of the thyroid gland upon the nervous system with neurologic-psychiatric symptoms are discussed. With hyperthyreosis in younger patients hyperactive and psychotic signs occur, in older patients so-called apathic thyreotoxicosis. Neurologically there appear acute and chronic thyreotoxic myopathies, paroxysmal paralyses, the so-called hyperthyreotic chorea and a series of disturbances of eye muscles. In a thyreotoxic crisis psychotic preliminaries may proceed to a coma. With hyperthyreoses there occur intellectual impairment, showing but also psychoses as well as multiple neurological defect syndromes and epileptic seizures. Neurological defects as a consequence of thyreostatic therapy are rare, mostly these are disturbances of periphal nerves.
[Treatment of diabetic ketoacidosis by means of adjusted insulin infusions].
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Studies on the mechanism of insulin action: basic concepts and clinical implications.
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[Development and correction of water-electrolyte and acid-base-equilibrium disorders in endocrine diseases (proceedings)].
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Glucose homeostasis under continuous intravenous insulin therapy in diabetics.
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On gluconeogenesis of human liver. Accelerated hepatic glucose formation induced by increased precursor supply.
In 8 subjects in whom portal vein catheters had been inserted 5-6 days previously during cholecystectomy, arterial and portal concentrations of glucose, lactate, pyruvate, glycerol, alanine, free fatty acids, beta-hydroxybutyrate and acetoacetate revealed no significant differences. This provided the basis for the calculation of hepatic balances from arterio-hepatic venous substrate-differences in 17 healthy volunteers. In eight of them metabolic balances were determined during elevated hepatic lactate supply. Kinetics of the substrates throughout the whole test period in 9 controls showed no gross interference from the catheterization or infusion procedure. The elevated hepatic lactate concentration caused a doubling of hepatic glucose output, which could almost entirely be accounted for by a fivefold increase of hepatic lactate uptake. This acceleration of hepatic gluconeogenesis was accompanied by a significant increment of hepatic free fatty acid uptake, whereas hepatic ketone body production did not change. These data seem to support the view that hepatic energy requirements caused by an accelerated gluconeogenesis might be covered from enhanced free fatty acid oxidation.
[Ketogenesis in lipatrophic diabetes and its susceptibility to insulin].
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