リフィーディング ショウコウグン

Refeeding syndrome is a potentially fatal medical condition that may affect malnourished patients in response to an inappropriately rapid overfeeding. This commonly occurs following the institution of nutritional support, especially parenteral or enteral nutrition. The most characteristic pathophysiology of refeeding syndrome relates to the rapid consumption of phosphate after glucose intake and subsequent hypophosphatemia. Refeeding syndrome can manifest as either metabolic changes （hypokalaemia, hypophosphataemia, vitamin B１deficiency, and altered glucose metabolism）or physiological changes（cardiac arrhythmias, unconsciousness, seizures, cardiac or respiratory depression） and potentially death. Preventing refeeding syndrome is the primary goal when initiating nutrition support in severely malnourished patients. Clinicians should be aware of refeeding syndrome when they treat malnourished patients, and most importantly take appropriate steps（careful monitoring）to prevent refeeding syndrome

Identification of protease serine S1 family member 53 as a mitochondrial protein in murine islet beta cells

The aim of this study was to identify genes that are specifically expressed in pancreatic islet β-cells (hereafter referred to as β-cells). Large-scale complementary DNA-sequencing analysis was performed for 3,429 expressed sequence tags derived from murine MIN6 β-cells, through homology comparisons using the GenBank database. Three individual ESTs were found to code for protease serine S1 family member 53 (Prss53). Prss53 mRNA is processed into both a short and long form, which encode 482 and 552 amino acids, respectively. Transient overexpression of myc-tagged Prss53 in COS-7 cells showed that Prss53 was strongly associated with the luminal surfaces of organellar membranes and that it underwent signal peptide cleavage and N-glycosylation. Immunoelectron microscopy and western blotting revealed that Prss53 localized to mitochondria in MIN6 cells. Short hairpin RNA-mediated Prss53 knockdown resulted in Ppargc1a downregulation and Ucp2 and Glut2 upregulation. JC-1 staining revealed that the mitochondria were depolarized in Prss53-knockdown MIN6 cells; however, no change was observed in glucose-stimulated insulin secretion. Our results suggest that mitochondrial Prss53 expression plays an important role in maintaining the health of β-cells

メタボリック ショウコウグン ニオケル コウケツアツ ノ カンリ

Metabolic syndrome includes abdominal obesity, hyperlipidemia, diabetes, and hypertension. All, but hypertension, are obviously related to metabolism. However, hypertension might result from, at least in part, abdominal obesity, because adipose tissue produces bioactive mediators （adipocytokines）which increase blood pressure. In treatment of hypertension, we should concern insulin resistance, which is a major risk factor of cardiovascular events. Angiotensin converting enzyme inhibitor is known to improve insulin resistance, but results of angiotensin receptor blocker in animal studies are controversial. In clinical trial, there are many established data that ARBs prevent new onset of diabetes mellitus, suggesting that this agent also has a beneficial effect on glucose metabolism. Short acting Ca-antagonists, such as nifedipine, decrease insulin sensitivity, but long-acting Ca-antagonists increase it. βblockers decrease insulin sensitivity but those with α-blocking action improve insulin resistance. Recent study, ARB is more potent to reduce cardiovascular risk in those with obesity than in those with normal body weight, suggesting some drugs are more effective in metabolic syndrome. Thus, when we chose antihypertensive drugs in treating patients with metabolic syndrome, we have to choose proper drugs in addition to modify life-style

Approach to novel functional foods for stress control : 3. Establishment of stress-resistant rat model and its mechanism

A stress-resistant rat model was introduced. SPORTS (Spontaneously-Running-Tokushima-Shikoku) rats showed significantly shorter time of immobility in the forced swim test compared to control Wister rats. Increase norepinephrine concentration secondary to decreased activity of monoamine oxidase A (MAOA) in hippocampus was observed in this model rats. This model rats are considered to be useful for studying the mechanism of psychological stress

The phytoestrogen ginsensoside Re activates potassium channels of vascular smooth muscle cells through PI3K/Akt and nitric oxide pathways

In vascular smooth muscle cells, large-conductance Ca2+-activated K+ channels (KCa channels) play a pivotal role in determining membrane potential, and thereby the vascular tone. Ginsenoside Re, a phytochemical from ginseng, is reported to activate this channel, but its precise mechanism is unsolved. Patch clamp studies showed that ginsenoside Re activates KCa channels in the arterial smooth muscle cell line A10 in a dose-dependent manner. The channel-opening effect of ginsenoside Re was inhibited by 1 μM L-NIO, an inhibitor of eNOS, but not by 3 μM SMTC, an inhibitor of nNOS, indicating that ginsenoside Re activated KCa channels through activation of eNOS. SH-6 (10 μM), an Akt inhibitor, and wortmannin, a PI3-kinase inhibitor, completely blocked activation of KCa channels by ginsenoside Re, indicating that it activates eNOS via a c-Src/PI3-kinase/ Akt-dependent mechanism. In addition, the ginsenoside Re-induced activation of eNOS and KCa channel was blocked by 10 μM ICI 182,780, an inhibitor of membrane estrogen receptor-α, suggesting that eNOS activation occurs via a non-genomic pathway of this receptor. In conclusion, ginsenoside Re releases NO via a membrane sex steroid receptors, resulting in KCa channel activation in vascular smooth muscle cells, promoting vasodilation and preventing severe arterial contraction

コウウンドウセイ モデル ラット SPORTS ノ カイバ ニオケル ノルエピネフリン ドウタイ ト ジハツ ウンドウリョウ

Reduced physical exercise activity contributes to the development of several metabolic disorders including obesity, type ２ diabetes and hypertension. Especially in the developed countries, many people choose not to be active physically, possibly because of a reduced motivation to participate in exercise activities. Thus, augmentation of exercise motivation and subsequent increase in the physical activity would reduce an incidence of these metabolic disorders. In order to clarify the psychological mechanisms responsible for an increased exercise activity, we have generated and established a line of SPORTS （Spontaneously-Running-Tokushima-Shikoku） rat for high levels of voluntary wheel running. Male SPORTS rats run voluntarily in the running wheel almost six times longer than control Wistar rats. Here we examined the relation of the running activity of SPORTS rat with the hippocampal norepinephrine （NE） system including the levels of NE, adrenergic receptors, and degradation enzymes for monoamines. In the hippocampus of SPORTS rats, the level of NE in extracellular fluid was augmented, whereas the level in the homogenate of the whole tissue was decreased even for sedentary conditions. The level of striatal dopamine has not altered in both groups. The protein expression and the activity levels of monoamine oxidase A （MAOA）, a critical enzyme for the degaradation of NE, were decreased in the hippocampus of SPORTS rats to increase extracellular NE level. Thus, inhibition of oxidase activity in normal Wistar rats markedly increased wheel running activity. Our results indicate that the hippocampal NE determines the neural basis of the psychological regulation of exercise behavior in SPORTS rats. Modulation of NE transmission in the hippocampus will be a good method for enhancing the exercise behavior both in clinical patients and in healthy humans

The nucleoside and nucleotide mixture (OG-VI) rescues intestinal-like epithelial cells from the cytotoxicity of chemotherapeutic agents

Immune cells and cells undergoing rapid turn-over can obtain exogenous nucleotides via salvage synthesis. We evaluated whether or not the balanced nucleoside and nucleotide mixture OG-VI, could rescue intestinal epithelial-like Caco-2 cells from the cytotoxic effects of several chemotherapeutic agents, in the presence and absence of glutamine (Gln). Cells were exposed to 5-fluorouracil (5FU), methotrexate (MTX) or 6-mercaptopurine (6MP), after which proliferation and cell cycle analyses were performed. Following exposure to the chemotherapeutic agents, we observed that cells treated with OG-VI proliferated well, whereas those without the supplement did not proliferate. Furthermore, following treatment with either 5FU or MTX, we observed that the number of cells in the G0/G1 phase decreased and those in the S phases increased. However, these cell cycle alterations were prevented by the addition of OG-VI. With the exception of 6MP-treated cells, we did not observe any effects on proliferation or cell cycle regulation that could be ascribed to the presence of Gln. Thus, we have demonstrated that OG-VI rescues cells from the cytotoxic effects of several chemotherapeutic agents

膵β細胞と膵α細胞の分化表現型はホメオティック遺伝子発現の差異と関連する

To identify the genes that determine differentiation phenotypes, we compared gene expression of pancreatic islet β- and α-cells, which are derived from the common precursor and secrete insulin and glucagon, respectively. The expression levels of homeotic genes including Hox genes known to determine region specificity in the antero-posterior (AP) body axis, tissue-specific homeobox genes, and other 8,734 genes were compared in a β- and α-cell line of MIN6 and αTC1.6. The expression of homeotic genes were surveyed with reverse transcription-polymerase chain reaction (RT-PCR) using degenerate primers corresponding to invariant amino acid sequences within the homeodomain and subsequently with specific primers. Expression of Hoxc6, Hoxc9, Hoxc10, Pdx1, Cdx2, Gbx2, Pax4, and Hlxb9 genes in MIN6 was higher than those in αTC1.6, while expression of Hoxa2, Hoxa3, Hoxa5, Hoxa6, Hoxa7, Hoxa9, Hoxa10, Hoxa13, Hoxb3, Hoxb5, Hoxb6, Hoxb13, Hoxb8, and Brain4 genes in αTC1.6 was higher than those in MIN6. Out of 8,734 mouse genes screened with high-density mouse cDNA microarrays for MIN6- and αTC1.6-derived cDNA, 58 and 25 genes were differentially over- and under-expressed in MIN6, respectively. GLUTag, which is derived from a large bowel tumor and expresses the proglucagon gene, showed a comparatively similar expression profile to that of αTC1.6 in both homeotic and other genes analyzed in cDNA microarray. Our results are consistent with the interpretation that not only the tissue-specific homeotic genes, but also Hox genes are related to differentiation phenotypes of pancreatic β- and α-cells rather than their regional specification of the body in vertebrates