尾加压素II与糖尿病

尾加压素II(urotensin II，UII)最早是从鱼尾部下垂体中分离出的调节肽，近来已从人体中克隆出来，并发现体内一种孤立的G蛋白偶联受体GPR14是其特异性受体。UII与GPR14结合后，参与许多生物学效应，如调节内分泌，调节渗透压平衡，调节胃肠道平滑肌及心血管收缩功能等，是迄今体内最强的缩血管活性肽。UII不仅与许多人类心血管疾病如高血压，充血性心力衰竭（CHF），冠心病和动脉粥样硬化有关，而且研究发现，糖尿病患者血液中UII含量升高。初步研究表明,UII的基因多态性和2型糖尿病的发生有关；尾加压素II还可抑制胰岛素的释放。     

p38 MAPK mediates cardiovascular and behavioral responses induced by central IL-1β and footshock in conscious rats

INTRODUCTION Sharing characteristics of stress mediators[1], cen-tral interleukin-1β (IL-1β) is very important in cardio-vascular and behavioral responses to stressors[2-4]. Itcan induce similar hypertensive responses to stress viacardiovascular regulatory regions[5]. We observed pre-viously that central IL-1β mediated cardiovascular re-sponses to some stressful stimuli, such as conditionedfear stimuli and footshock[6]. Many stressful stimulimay increase IL-1β mRNA expression and …     

Effects of dietary fiber and protein on rat erythrocyte insulin-receptor interaction

The metabolic effects of cellulose on insulin receptor interaction (IRI) was studied at 10 and 20 percent protein levels in male weanling Sprague Dawley rats. One hundred and four (104) rats were divided into 8 groups of 13 each and randomly put on various dietary treatments as already reported elsewhere [Fed. Proceed. 1985; 44(5):6367]. Animals for radioreceptor studies (n=5 per group) were fed for 8 weeks. Blood samples were obtained from the rats via cardiac puncture under nembutal anesthesia. Erythrocyte IRI and serum insulin levels (IN) were measured by a standardized radioreceptor assay (10) and radioimmunoassay respectively. Fiber and protein intake had significant effect on IRI (p<0.01) and IN (p<0.05). Specific percent 125_I-insulin binding (SIB) was higher in the 20% protein group at all fiber levels while in the fiber free groups higher SIB was observed in the 10% protein group (p<0.01). At both protein levels, maximum SIB was observed at the 5% fiber level. While SIB in the absence of fiber was observed to be strictly a function of receptor site concentration (Ro) binding in the presence of fiber was a function of both Ro and empty site affinity (Ke). Fiber intake appears to interfere with the negative cooperative nature of the receptor sites by slowing down the rate of changing affinity from a high Ke to the limiting K_f (filled site affinity) state as receptor occupancy [Y=Long [B]/Ro] increases. While no significant effect of calorie was observed on e and _f, caloric intake (Cal) showed a positive correlation (r=0.8, p<0.001) with IN and a negative (r=0.32, p<0.02) correlation with Ro. It is concluded that: (I) diet can modulate erythrocyte IRI in growing animals, (II) the metabolic effects of dietary fiber depend on the combination with other nutrients, (III) adequate protein nutrition is essential for plasma membrane function at the cell receptor level in growing animals and (IV) the increase in IRI by dietary fiber is a function of both e, Ro and the sustenance of the average affinity of these homogeneous class of receptor sites in the high affinity states.     

Glutamate-containing dipeptides do not modulate ligand binding at excitatory amino acid receptors

Dipeptides of the structure X-Glu (e.g. X = Phe, Leu) have been proposed as allosteric modulators of excitatory amino acid receptors in rat brain membranes. Here we report that these dipeptides reduce the binding of L-[3H]Glu (predominantly N-methyl-D-aspartate-sensitive sites) and of [3H]kainate to postsynaptic density preparations isolated from rat brain. However, several observations indicate that the effects of these dipeptides are mediated not by allosteric modulation, but by free L-Glu liberated by the actions of a membrane-associated aminopeptidase. The absolute and relative potencies of the dipeptides are similar at all acidic amino acid binding sites examined to date, suggesting the involvement of a factor with similar activity at each site (e.g. L-Glu). N-Acetyl-Met-Glu is a weak inhibitor of L-Glu and kainate binding, and N-blocked peptides are known to be poor substrates of aminopeptidases. Bestatin, an inhibitor of aminopeptidases, decreases or abolishes the effects of substrate dipeptides on L-Glu and kainate receptor binding, while having no effect itself.     

Extracellular ATP promotes angiogenesis and adhesion of TNBC cells to endothelial cells via upregulation of CTGF

Our previous works have indicated that extracellular ATP is an important prometastasis factor. However, the molecular mechanism involved needs to be further studied. We demonstrated that extracellular ATP treatment could upregulate the expression of connective tissue growth factor (CTGF) in both triple‐negative breast cancer (TNBC) cells and endothelial cells (ECs). Extracellular ATP stimulated the migration of TNBC cells and ECs, and angiogenesis of ECs via the P2Y2––YAP‐CTGF axis. Furthermore, we demonstrated that adenosine triphosphate (ATP) stimulated TNBC cell adhesion to ECs and transmigration through the EC layer via CTGF by upregulation of integrin β1 on TNBC cells and VCAM‐1 on ECs. Both apyrase (ATP‐diphosphohydrolase) and CTGF shRNA treatments could inhibit the metastasis of inoculated tumors to lung and liver in a mouse model, and these treated tumors had fewer blood vessels. Collectively, our data indicated that extracellular ATP promotes tumor angiogenesis and the interactions between TNBC cells and ECs through upregulation of CTGF, thereby stimulating TNBC metastasis. The pleiotropic effects of ATP in angiogenesis and cell adhesion suggest that extracellular ATP or CTGF could be an effective target for TNBC therapy.