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Biomedical subjects

U Keller

Publications and source records attributed to U Keller.

At least 271 records · Page 15Linked to original sources
PubMed1984

Stimulatory effect of norepinephrine on ketogenesis in normal and insulin-deficient humans.

Elevation of plasma norepinephrine concentrations to stress levels (1,800 pg/ml) resulted in normal subjects in a significant increase in ketone body production by 155% (determined by use of [14C]acetoacetate infusions), in a decrease of the metabolic clearance rate by 38%, hyperketonemia, and in increased plasma free fatty acid (FFA) levels by 57% after 75 min. Norepinephrine infusion during somatostatin-induced insulin deficiency resulted in an augmented and sustained increase in ketone body concentrations due to increased production and decreased peripheral clearance of ketone bodies. Norepinephrine's stimulatory effect on lipolysis waned with time, and its effect on ketogenesis in normal subjects was greater than its influence on plasma FFA levels, and thus presumably on hepatic FFA uptake, suggesting a direct stimulatory effect on hepatic ketogenesis. The data demonstrate that in normal humans the hyperketonemic effect of elevated plasma norepinephrine concentrations results from a combination of three factors: increased ketone body production from augmented FFA supply to the liver; accelerated hepatic ketogenesis; and modestly decreased metabolic clearance of ketone bodies. Acute insulin deficiency augments all these effects and results in progressive ketosis.

Acute Disease↗
PubMed1984

Effect of epinephrine and somatostatin-induced insulin deficiency on ketone body kinetics and lipolysis in man.

The effect of elevated plasma epinephrine concentrations (approximately equal to 800 pg/ml) on ketone body kinetics was determined in postabsorptive normal subjects using primed-continuous infusions of 3-14C-acetoacetate. Infusion of epinephrine (60 ng/kg/min) resulted in a transient increase in total ketone body production to a maximum of 2.5-fold the basal rate within 45 min (P less than 0.01 versus controls). Ketone body uptake increased with a delay, compared with production, causing a 2.8-fold increase in total ketone body concentrations (P less than 0.05 versus controls). Plasma free fatty acid (FFA) and blood glycerol concentrations increased transiently during epinephrine; their course was similar to that of ketone body production. Epinephrine administration resulted in hyperglycemia, hyperlactatemia, and a modest increase in plasma insulin and glucagon concentrations. To assess epinephrine's effect on ketone body kinetics during lack of insulin, and to avoid epinephrine-induced alterations in plasma insulin and glucagon concentrations, epinephrine was also infused combined with somatostatin (6.5 micrograms/kg/h). During somatostatin infusion, epinephrine administration resulted in an enhanced and sustained elevation of total ketone body production from 4.4 +/- 0.8 to 15.1 +/- 1.2 mumol/kg/min (P less than 0.01 versus somatostatin alone). Ketone body concentrations increased markedly from 310 +/- 63 to 1763 +/- 137 mumol/L (P less than 0.01 versus somatostatin alone); the ketonemic effect was enhanced due to a 40% decrease of the metabolic clearance rate associated with somatostatin infusion. The increase in plasma FFA and blood glycerol concentrations during somatostatin-induced insulin deficiency was transiently enhanced by epinephrine, such that they increased to 3.2- and 5.6-fold their basal values after 45 min, respectively (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1983

[A slide program on hypertension and obesity: a simple method of patient information].

It is well established that information on their disease is one of the prerequisites for improvement of patients' compliance with therapy. The authors have therefore developed a simple slide program presenting information on hypertension and obesity. Consisting of 52 slides, it was shown in the central waiting room of the medical outpatient department at the University Hospital, Zurich. In order to assess learning, 841 patients were asked to fill in a questionnaire. 485 had seen the program and 356 served as controls with the program switched off. Four main results emerged: 1. The percentage of subjects scoring greater than or equal to 4 correct answers (of a maximum of 5) rose significantly from 22.6% to 64.2%. 2. The number of incorrect answers (maximum 3) remained unchanged. 3. Learning decreased with age. 4. Occupation did not have a significant effect on learning. The results clearly show that the program represents an effective method of teaching patients and may therefore serve to improve compliance with therapy.

Adult↗
PubMed1983

[Oral antidiabetic agents: recent aspects].

Sulfonylureas are the most potent and widely used oral antidiabetic agents. Despite the finding of possible side effects in a large multicenter trial (UGDP Study) demonstrating increased cardiovascular mortality during tolbutamide therapy, prescription of sulfonylureas has not declined in view of the inconclusive results of the study. In addition, new aspects of their mode of action have been discovered. Sulfonylureas may enhance insulin sensitivity of peripheral tissues, particularly by raising the decreased number of insulin receptors in type II diabetics. While this extrapancreatic effect appears to be quantitatively important, it is only present when insulin secretion is simultaneously stimulated. Insulin release is enhanced due to an increase in the sensitivity of the B-cell to glucose challenge. There is evidence to suggest that the extrapancreatic effect of sulfonylureas is secondary to their pancreatic effect. Pointers in the same direction emerged from our own results in a study on the influence of sulfonylureas added to insulin therapy on insulin sensitivity in type I diabetics. Sulfonylureas failed to increase insulin sensitivity and insulin requirements in these patients. The first generation compounds of sulfonylureas are associated with more side effects and drug interactions than the second generation preparations. However, the latter are more frequently associated with hypoglycemia since they are more potent and have a prolonged duration of action. Biguanides have almost fallen into disuse as therapeutic agents due to the potentially lethal complication of lactic acidosis. Only metformin may still be indicated in certain cases. Inhibitors of intestinal amylase and glucosidase represent a new therapeutic principle in diabetes therapy whose aim is to reduce postprandial hyperglycemia. Their value as therapeutic agents is not yet clearly established.

Administration, Oral↗
PubMed1983

Mechanism of depsipeptide formation catalyzed by enniatin synthetase.

Covalently bound intermediates of enniatin B synthesis could be isolated from enniatin synthetase by treatment with performic acid. By comparison with products of mild alkaline cleavage of authentic enniatin B they could be identified as the dipeptide D-2-hydroxyisovaleryl-N-methylvaline and the corresponding tetrapeptide. Synthesis of enniatins apparently proceeds via condensation of dipeptides. This was confirmed by the use of the substrate analogue isovaleric acid, which has shown to be a strong inhibitor for enniatin synthesis by formation of N-isovaleryl-N-methyl valine.

Anti-Bacterial Agents↗
PubMed1983

Studies of protoplast fusion in Streptomyces chrysomallus.

Conditions for the regeneration of cells from protoplasts of Streptomyces chrysomallus, a producer of the peptide antibiotic actinomycin, are described. Regeneration of fusion products was most efficient at 27-30 degrees C on regeneration R2 medium (Okanishi et al., 1974) containing 0.25 M-sucrose. The addition of phosphate (150-300 mg 1(-1) to the medium and incubation at 23 degrees C proved to be optimal for the regeneration of individual strains. Highest recombination frequencies after protoplast fusion were obtained by fusing protoplasts in the presence of 45% (w/v) polyethylene glycol 6000. With strains that produce no, or little antibiotic, protoplasts must be present in excess in fusion mixtures in order to overcome inhibition of regeneration by the antibiotic-producing partner.

Dactinomycin↗
PubMed1983

Highly Efficient Mutagenesis of Claviceps purpurea by Using Protoplasts.

Claviceps purpurea ATCC 20102, which is aconidial under laboratory conditions, was grown in submerged culture in the presence of mutagens and various nutritional additives. Protoplasts from such cultures were prepared and regenerated on solid medium to obtain colonies from single cell units. Frequencies of auxotrophs and high alkaloid producers were on the order of 1 to 2%. Some of the auxotrophic mutants derived from strain ATCC 20102 were constantly segregating prototrophs. High-alkaloid-producing derivatives showed sclerotia-like morphology and violet-brown pigmentation, in contrast to the parent strain; some of them also showed segregation sectors when grown as giant colonies. Mutagenesis of strain 1029, isolated during this study and having an increased level of alkaloid synthesis and sclerotia-like cell morphology, was done in the same fashion as with the original parent strain, ATCC 20102. Mutants obtained from this strain were all stable with respect to their genotypes. However, a large proportion of colonies derived from regenerated protoplasts, even in the mutagen-free controls, showed a lowered level of alkaloid production and were morphologically more similar to the original wild type, ATCC 20102. The influence of protoplast preparation or regeneration or both on the stability of genes involved in differentiation is discussed.

Journal Article↗
PubMed1983

Role of glucagon in enhancing ketone body production in ketotic diabetic man.

To assess the role of endogenous glucagon in regulating hepatic ketone body production in ketotic insulin-withdrawn diabetic subjects, ketone body kinetics were determined in two groups of C-peptide-negative diabetics 6 h after interruption of a s.c. insulin infusion. In group 1 (N = 5), glucagon levels were suppressed by infusion of somatostatin (SRIF), whereas in group 2 (N = 6) glucagon was replaced during SRIF by infusing glucagon at 2 ng/kg/min. Ketone body production rates as determined by primed-continuous infusion of [3-14C]acetoacetate declined from 19.5 +/- 0.8 to 16.4 +/- 0.4 mumol/kg/min (P less than 0.01) during 105 min of SRIF-induced glucagon suppression, whereas they remained unchanged (+0.2 +/- 0.4 mumol/kg/min, P less than 0.01 compared with SRIF) during glucagon replacement. Total ketone body concentrations remained unchanged during SRIF infusion but increased from 2.2 +/- 0.3 to 2.9 +/- 0.2 mmol/L (P less than 0.01) during glucagon replacement. The metabolic clearance rate of total ketone bodies declined significantly (P less than 0.01) by 27% and 21% in the two groups. Plasma free fatty acid and glycerol concentrations remained unchanged in both groups whereas plasma glucose decreased by 3.2 +/- 0.5 mmol/L during SRIF (P less than 0.01). Thus, endogenous glucagon contributed significantly to the maintenance of ketone body production rates in ketotic insulin-deficient diabetics. Since ketogenesis was altered in the absence of changes in free fatty acid levels, the results suggested that glucagon enhanced ketogenesis by an intrahepatic effect.

Adolescent↗