While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis. Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake. Further, metformin suppresses glucagon signaling in the liver by suppressing adenylate cyclase which leads to suppression of gluconeogenesis. In addition, metformin reduces autophagy failure observed in pancreatic β-cells under diabetic conditions. Furthermore, it is known that metformin alters the gut microbiome and facilitates the transport of glucose from the circulation into excrement. It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15). Furthermore, much attention has been drawn to the fact that the frequency of various cancers is lower in subjects taking metformin. Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. It has been shown recently that metformin consumption potentially influences the mortality in patients with type 2 diabetes mellitus and coronavirus infectious disease (COVID-19). Taken together, metformin is an old drug, but multifaceted mechanisms of action of metformin have been unraveled one after another in its long history. 相似文献
The finite-difference time-domain (FDTD) simulations of specific absorption rate (SAR) in a human head exposed to microwaves have, to date, been carried out on models of the head only. This was because it was believed that the body effects on the average SAR of the head could be ignored at high frequencies of around 1 GHz. That opinion, however, was based on inappropriate calculation conditions and is therefore unreliable. In this paper, we have re-examined the body effects on the SAR distributions in a realistic homogeneous model of the adult head exposed to microwaves. We found that the SAR on the eye surface of the head-only model exposed to E-polarized waves was 31% smaller than that of the whole-body model at 900 MHz, and 43% larger at 1.5 GHz. For a size that can practically be considered whole-body, it is necessary to have the top of the head to the belly for 900 MHz and to the chest area for 1.5 GHz. The previously unclear body effects of H-polarized waves were assumed to be less than those of E-polarized waves, suggesting that the chest area would be sufficient for both frequencies. 相似文献
Hepatitis B virus (HBV) carriers with antibody to hepatitis e antigen comprise asymptomatic carriers (ASCs), who have low replication levels of HBV, and patients with chronic active hepatitis (CAH), who have high levels of viral replication. To investigate whether defects in the X protein might be responsible for this difference in the level of viral replication, nucleotide sequences of X and precore gene regions in serum HBV were analyzed in 19 ASCs and 9 CAH patients. All patients had a point mutation creating a stop codon in the precore region. Seventeen ASCs (87.3%) had identical mutations consisting of 4 noncontiguous 1-bp deletions or an 8-bp deletion, both of which truncate the normal X protein, whereas no CAH patient had an X gene mutation (P < .001). Thus, deletion of the X protein might be responsible for the low levels of viral replication in ASCs. 相似文献
The purpose of the study was to explore the relationship between the exposure of adolescents in the seventh and eighth grades to cigarette advertising and their being smokers. A survey questionnaire given to 602 adolescents assessed their exposure to cigarette advertising and provided measures of their smoking behavior, demographic characteristics, and some psychosocial variables. The results indicated that exposure to cigarette advertising and having friends who smoked were predictive of current smoking status. Adolescents with high exposure to cigarette advertising were significantly more likely to be smokers, according to several measures of smoking behavior, than were those with low exposure to cigarette advertising. The findings extend previous research identifying factors that may play a role in the initiation and maintenance of smoking among adolescents. 相似文献
A development of 170GHz/500kW level gyrotron was carried out as R&D work of ITER. The oscillation mode is TE31,8. In a short pulse experiment, the maximum power of 750kW was achieved at 85kV/40A. The efficiency was 22%. In the depressed collector operation, 500kW/36%/50ms was obtained. The maximum efficiency of 40% was obtained at PRF=470kW whereas the power decrease by the electron trapping was observed. Pulse extension was done up to 10s at PRF=170kW with the depressed collector operation. The power was limited by the temperature increase of the output window. 相似文献
Carboxymethyl-2-diethylaminoethylcellulose (CM-DEAE cellulose) was prepared by etherification of carboxymethylcellulose with diethylaminoethyl chloride in a NaOH solution. The behaviour of CM-DEAE cellulose in aqueous solution was studied by viscosity and GPC measurements. The degree of substitution (DS) and existing states of DEAE substituents were examined by the use of proton NMR, and those of the CM substituents were observed with FT-IR. The results reveal that the reduced viscosity and apparent molecular size of CM-DEAE cellulose vary with the concentration of sodium chloride and changes in pH and DS. These phenomena can be explained in terms of inter- and intra-molecular ionic interactions. 相似文献
This study deals with the impact property and damage tolerance of matrix hybrid composite laminates with different laminate constitution. The matrix hybrid composite laminates consisted of the laminae with a conventional epoxy resin and the laminae with a flexible epoxy resin modified from the conventional resin to avoid the interlaminar delamination. The impact energy absorption ratio greatly depended on the matrix resin placed at the impact face. The energy absorption was almost constant if the conventional resin was placed at the impact surface layer, while it increased exponentially with the increasing fraction of the flexible resin if the flexible resin was placed at the impact face. The impact energy was absorbed by the damage development and propagation in the laminate with conventional resin laminae as the impacted face, while it was absorbed by both the recoverable deformation of the flexible resin and the damage propagation in the laminate with flexible resin laminae as the impacted face. 相似文献