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51.
52.
H S Moeniralam F Sprangers E Endert M T Ackermans J J Van Lanschot H P Sauerwein J A Romijn 《Journal of applied physiology》2001,91(1):130-136
The purpose of the present in vivo study was to determine the role of nitric oxide (NO) in the regulation of glucose metabolism in response to endotoxin by blocking NO synthesis with N(G)-monomethyl-L-arginine (L-NMMA). In five dogs, the appearance and disappearance rates of glucose (by infusion of [6,6-(2)H(2)]glucose), plasma glucose concentration, and plasma hormone concentrations were measured on five different occasions: saline infusion, endotoxin alone (E coli, 1.0 microg/kg i.v.), and endotoxin administration plus three different doses of primed, continuous infusion of L-NMMA. Endotoxin increased rate of appearance of glucose from 13.7 +/- 1.6 to 23.6 +/- 3.3 micromol x kg(-1) x min(-1) (P < 0.05), rate of disappearance of glucose from 13.9 +/- 1.1 to 24.8 +/- 3.1 micromol x kg(-1) x min(-1) (P < 0.001), plasma lactate from 0.5 +/- 0.1 to 1.7 +/- 0.1 mmol/l (P < 0.01), and counterregulatory hormone concentrations. L-NMMA did not affect the rise in rate of appearance and disappearance of glucose, plasma lactate, or the counterregulatory hormone response to endoxin. Plasma glucose levels were not affected by endotoxin with or without L-NMMA. In conclusion, in vivo inhibition of NO synthesis by high doses of L-NMMA does not affect glucose metabolism in response to endotoxin, indicating that NO is not a major mediator of glucose metabolism during endotoxemia in dogs. 相似文献
53.
A M Pereira Arias P H Bisschop M T Ackermans E Endert J A Romijn H P Sauerwein 《Hormones et métabolisme》2001,33(11):659-663
In healthy subjects, basal endogenous glucose production is partly regulated by paracrine intrahepatic factors. It is currently unknown whether paracrine intrahepatic factors also influence the increased basal endogenous glucose production in patients with type 2 diabetes mellitus. Administration of indomethacin to patients with type 2 diabetes mellitus stimulates endogenous glucose production and inhibits insulin secretion. Our aim was to evaluate whether this stimulatory effect on glucose production is solely attributable to inhibition of insulin secretion. In order to do this, we administered indomethacin to 5 patients with type 2 diabetes during continuous infusion of somatostatin to block endogenous insulin and glucagon secretion and infusion of basal concentrations of insulin and glucagon in a placebo-controlled study. Endogenous glucose production was measured 3 hours after the start of the somatostatin, insulin and glucagon infusion, for 4 hours after administration of placebo/indomethacin, by primed, continuous infusion of [6,6-(2)H(2)] glucose. At the time of administration of placebo or indomethacin, there were no significant differences in plasma glucose concentrations and endogenous glucose production rates between the two experiments (16.4 +/- 2.09 mmol/l vs. 16.6 +/- 1.34 mmol/l and 17.7 +/- 1.05 micromol/kg/min and 17.0 +/- 1.06 micromol/kg/min), control vs. indomethacin). Plasma glucose concentration did not change significantly in the four hours after indomethacin or placebo administration. Endogenous glucose production in both experiments was similar after both placebo and indomethacin. Mean plasma C-peptide concentrations were all below the detection limit of the assay, reflecting adequate suppression of endogenous insulin secretion by somatostatin. There were no differences in plasma concentrations of insulin (76 +/- 5 vs. 74 +/- 4 pmol/l) and glucagon (69 +/- 8 vs. 71 +/- 6 ng/l) between the studies with levels remaining unchanged in both experiments. Plasma concentrations of cortisol, epinephrine, and norepinephrine were similar in the two studies and did not change significantly. We conclude that indomethacin stimulates endogenous glucose production in patients with type 2 diabetes mellitus by inhibition of insulin secretion. 相似文献
54.
Amoresano A; Andolfo A; Siciliano RA; Mele A; Coscarella A; De Santis R; Mauro S; Pucci P; Marino G 《Glycobiology》1998,8(8):779-790
MEN 11300 is a hybrid glycoprotein of 297 amino acids obtained by fusion of
the cDNA encoding GM-CSF with the cDNA encoding EPO followed by
transfection of the hybrid gene into CHO cells. The oligonucleotide
construct incorporated a spacing sequence between the two individual cDNAs
which encodes eight amino acids constituting a linker peptide intended to
separate the GM-CSF and EPO moieties. The recombinant MEN 11300 protein was
submitted to a detailed structural characterization including the
verification of the entire amino acid sequence, the assignment of the
disulfide bridges pattern, the identification of the glycosylation sites
and the definition of the glycosidic moiety, including site-specificity.
Partial processing of the C-terminal Arg residue and the occurrence of
N-glycosylation sites at Asn27, Asn155, Asn169, Asn214 were established.
Moreover, O-glycosylation at Ser257 and at the N-terminal region was also
detected. A large heterogeneity was observed in the N-glycans due to the
presence of differently sialylated and fucosylated branched complex type
oligosaccharides whereas O-linked glycans were constituted by GalGalNAc
chains with a different number of sialic acids. The disulfide bridges
pattern was established by direct FABMS analysis of the proteolytic digests
or by ESMS analysis of HPLC purified fractions. Pairing of the eight
cysteine residues resulted in Cys54-Cys96, Cys88-Cys121, Cys138-Cys292, and
Cys160-Cys164. This S-S bridges pattern is identical to that occurring in
the individual natural GM-CSF and EPO, thus showing that the two protein
moieties in MEN 11300 can independently acquire their native
three-dimensional structure.
相似文献
55.
Unusual pattern of bacterial ice nucleation gene evolution 总被引:5,自引:0,他引:5
Edwards AR; Van den Bussche RA; Wichman HA; Orser CS 《Molecular biology and evolution》1994,11(6):911-920
Bacterial ice nucleation activity (INA+ phenotype) can be traced to the
product of a single gene, ina. A remarkably sparse distribution of this
phenotype within three bacterial genera indicates that the ina gene may
have followed an unusual evolutionary path. Southern blot analyses, coupled
with assays for ice-nucleating ability, revealed that within four bacterial
species an ina gene is present in some strains but absent from others.
Results of hybridization experiments using DNA fragments that flank the ina
gene suggested that the genotypic dimorphism of ina may be anomalous. A
phylogenetic analysis of 16S ribosomal RNA gene sequences from a total of
14 ina+ and ina- bacterial strains indicated that the ina+ bacteria are not
monophyletic but instead phylogenetically interspersed among ina- bacteria.
The relationships of ina+ bacteria inferred from ina sequence did not
coincide with those inferred from the 16S data. These results suggest the
possibility of horizontal transfer in the evolution of bacterial ina genes.
相似文献
56.
57.
Light-induced absorbance changes were measured at low temperatures in reaction center preparations from Rhodopseudomonas sphaeroides. Absorbance difference spectra measured at 100 °K show that ubiquinone is photoreduced at this temperature, both by continuous light and by a short actinic flash. The reduction occurred with relatively high efficiency. These results give support to the idea that ubiquinone is involved in the primary photochemical reaction in Rhodopseudomonas sphaeroides. Reduction of ubiquinone was accompanied by a shift of the infrared absorption band of bacteriopheophytin.The rate of decay of the primary photoproducts (P+870 and ubisemiquinone) appeared to be approximately independent of temperature below 180 °K and above 270 °K; in the region between 180 and 270 °K it increased with decreasing temperature. The rate of decay was not affected by o-phenanthroline. Secondary reactions were inhibited by lowering the temperature.The light-induced absorbance changes were inhibited by chaotropic agents, like thiocyanate and perchlorate. It was concluded that these agents lower the efficiency of the primary photoconversion. The kinetics indicated that the degree of inhibition was not the same for all reaction centers. The absorption spectrum of the photoconverted reaction centers appeared to be somewhat modified by thiocyanate. 相似文献
58.
Buijs MM Romijn JA Burggraaf J de Kam ML Frölich M Ackermans MT Sauerwein HP Cohen AF Meinders AE Pijl H 《American journal of physiology. Endocrinology and metabolism》2004,287(1):E63-E68
It has been suggested that (abdominally) obese individuals are hypersensitive to growth hormone (GH) action. Because GH affects glucose metabolism, this may impact glucose homeostasis in abdominal obesity. Therefore, we studied the effect of GH on glucose metabolism in abdominally obese (OB) and normal-weight (NW) premenopausal women. A 1-h intravenous infusion of GH or placebo was randomly administered to six NW [body mass index (BMI) 21.1 +/- 1.9 kg/m(2)] and six OB (BMI 35.5 +/- 1.5 kg/m(2)) women in a crossover design. Insulin, glucagon, and GH secretion were suppressed by concomitant infusion of somatostatin. Glucose kinetics were measured using a 10-h infusion of [6,6-(2)H(2)]glucose. In both groups, similar physiological GH peaks were reached by infusion of GH. GH strongly stimulated endogenous glucose production (EGP) in both groups. The percent increase was significantly greater in OB than in NW women (29.8 +/- 11.3 vs. 13.3 +/- 7.4%, P = 0.014). Accordingly, GH responsiveness, defined as the maximum response of EGP per unit GH, was increased in OB vs. NW subjects (6.0 +/- 2.1 vs. 2.2 +/- 1.5 micromol.min(-1).mU(-1).l(-1), P = 0.006). These results suggest that the liver is hyperresponsive to GH action in abdominally obese women. The role of the somatotropic ensemble in the control of glucose homeostasis in abdominal obesity is discussed. 相似文献
59.
60.