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Kyungtae Kim Sung Chun Cho Anthony Cova Ik Soon Jang Sang Chul Park 《Experimental & molecular medicine》2009,41(5):334-340
The effects of glucagon and epinephrine on gluconeogenesis in young (4 month) and old (24 month) Fisher 344 rat hepatocytes were compared. In contrast to glucagon, which had a similar effect on gluconeogenesis in both young and old cells, epinephrine caused a smaller increase in gluconeogenesis in old rat hepatocytes than in young hepatocytes. β2 adrenergic receptor (β2-AR) expression slightly decreased in aged rat liver, and there were differences between young and old hepatocytes in their patterns of G protein coupled receptor kinases, which are involved in the activation of β2-AR receptor signal desensitization. The major isoform of the kinase changed from GRK2 to GRK3 and the expression of β-arrestin, which is recruited by the phosphorylated β2-AR for internalization and degradation, increased in aged rat liver. GRK3 overexpression also decreased the glucose output from young rat hepatocytes. We conclude that an age-associated reduction in epinephrine-induced gluconeogenesis occurs through the epinephrine receptor desensitizing system. 相似文献
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Andrea Orlandin Ivan Guryanov Lucia Ferrazzano Barbara Biondi Francesca Biscaglia Claudia Storti Marzio Rancan Fernando Formaggio Antonio Ricci Walter Cabri 《Molecules (Basel, Switzerland)》2022,27(13)
The suppression of side reactions is one of the most important objectives in peptide synthesis, where highly reactive compounds are involved. Recently, the violuric acid derivative Oxyma-B was introduced into peptide synthesis protocols as a promising additive to efficiently control the optical purity of the amino acids prone to racemization. However, we discovered a side reaction involving the Beckmann rearrangement of Oxyma-B during the coupling reaction, which compromises the yield and purity of the target peptides. Here, we present the investigation of the mechanism of this rearrangement and the optimization of the coupling reaction conditions to control it. These results can be taken into account for the design of novel efficient oxime-based coupling reagents. 相似文献
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Zhongli Bao Ya-Chi Cheng Justin Jun Wei Mary Ziping Luo Jack Yongfeng Zhang 《Molecules (Basel, Switzerland)》2022,27(22)
Glucagon, a 29-amino acid polypeptide hormone, is an essential therapeutic agent used in the emergency treatment of hypoglycemia. However, glucagon is inherently unstable in aqueous solution. While glucagon equilibrates between unordered and the secondary α-helix state in solution, it can quickly transform into a different secondary β-sheet-rich amyloid-like fibril/oligomer structure under various conditions. Since changes in the secondary structure of glucagon can cause significant impacts, structure analysis is necessary and essential to assess the safety of the product. This study analyzed the secondary structure of glucagon products at the release and at the expiry using circular dichroism spectroscopy (CD) and 2D Nuclear Overhauser effect spectroscopy (2D NOESY). In order to also determine if structural differences exist between glucagon produced through different manufacturing processes, synthetic and recombinant glucagon products were used and compared. The CD results indicated that for all release and expired glucagon products, the structure compositions were 14 to 16% α-helix, 17 to 19% β-strand, 14 to 15% Turn, and 53 to 54% Unordered. This was consistent with the 2D NOESY analysis which showed that both products had an approximate α-helix composition of 14 to 17%. Overall, there were no significant differences in terms of the secondary structure between synthetic and recombinant glucagon products both at the release and at the expiry. 相似文献
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Hideaki Ichiba Tomoko Ogawa Takehiko Yajima Takeshi Fukushima 《Biomedical chromatography : BMC》2009,23(10):1051-1058
Structural modification of a polypeptide hormone, glucagon, by a hydroxyl radical in vitro was investigated by reversed‐phase high‐performance liquid chromatography (RP‐HPLC), and the oxidized site of glucagon was detected by electrospray ionization tandem mass spectrometry (ESI‐MS/MS). It was shown that 27methionine (Met) was oxidized to 27Met sulfoxide by hydroxyl radical, and the production rate of 27Met sulfoxide was faster than that by hydrogen peroxide. In addition, production of 27Met sulfoxide enantiomer was confirmed by RP‐HPLC analysis. cAMP production in a HepG2 cell induced by 27Met sulfoxide glucagon was reduced to approximately 75% as compared with that induced by the native form of glucagon. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
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M. A. Zewail N. M. Fahmy J. H. Nielsen 《Isotopes in environmental and health studies》2013,49(8):304-305
Since epinephrine and insulin are known to counteract each other in several metabolic respects, it was found of interest to evaluate the interaction of these hormones on glucose metabolism in isolated fat cells. Results indicate that in spite of reduced lipolysis, insulin potentiates the conversion of glucose to glyceride-glycerol. This means that a certain degree of esterification of fatty acids must take place. So the low rate of lipolysis is sufficient to provide fatty acids for this esterification. 相似文献
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为了寻找新型的抗糖尿病分子,以苯乙双胍为前体,制备了苯乙双胍铬(III)配合物.通过元素分析、摩尔电导率、电喷雾质谱、红外光谱、紫外可见光谱和核磁共振波谱对配合物的结构进行了表征,并研究了配合物在不同温度、不同pH值下溶液的稳定性、与H2O2的反应性和形貌.同时,构建了糖尿病C57小鼠模型,研究了其生物活性和毒性.结果证明,配合物对其活性指标均有好的抑制作用,保留了苯乙双胍的降糖性质,对机体是无毒的,并且通过MTT(3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐)实验说明配合物的生物相容性较好,实现了金属配合物降糖与控脂的多功能化应用.在此基础上,通过光谱法研究了配合物与胰高血糖素的相互作用,表明配合物对胰高血糖素是静态猝灭以较强的作用力结合,条件结合常数为1.29×105 L·mol-1,结合位点数约为1,初步提出了配合物的新的降糖机制. 相似文献
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G. A. Agaeva 《Journal of Applied Spectroscopy》2005,72(3):447-453
The spatial structure of glucagon in various solvents has been investigated by comparison of its circular-dichroism spectra
and the data of their theoretical conformational analysis. The theoretical conformational analysis of data on glucagon segments
made it possible to exactly determine their location in the ordered secondary structure of this peptide in various media.
It is shown that in a receptor-biophase medium, glucagon forms conformations with a large α-spiral segment.
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Translated from Zhurnal Prikladnoi Spektroskopii, Vol. 72, No. 3, pp. 416–421, May–June, 2005. 相似文献
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