Somatostatin: hypothalamic inhibitor of the endocrine pancreas

Somatostatin, a hypothalamic peptide that inhibits the secretion of pituitary growth hormone, inhibits basal insulin secretion in fasted cats and rats. In fasted baboons both basal and arginine-stimulated secretion of insulin and glucagon are inhibited. Somatostatin appears to act directly on the endocrine pancreas. The action is dose-related, rapid in onset, and readily reversed.     

Pathways of protein secretion in eukaryotes

Protein secretion from cells can take several forms. Secretion is constitutive if proteins are secreted as fast as they are synthesized. In regulated secretion newly synthesized proteins destined for secretion are stored at high concentration in secretory vesicles until the cell receives an appropriate stimulus. When both constitutive and regulated protein secretion can take place in the same cell a mechanism must exist for sorting the correct secretory protein into the correct secretory vesicle. The secretory vesicle must then be delivered to the appropriate region of plasma membrane. Transfection of DNA encoding foreign secretory proteins into regulated secretory cells has provided insight into the specificity of sorting into secretory vesicles.     

Insulin secretion by anomers of d-glucose

Isolated rat islets were incubated for 5 minutes in the media containing either the alpha or beta anomer of D-glucose (2 milligrams per milliliter). The amounts of secreted insulin and changes of anomers ratio were concomitantly determined. In spite of rapid mutarotation, significantly greater stimulation of insulin secretion was observed by alpha-D-glucose as compared with beta-D-glucose.     

鸡卵泡颗粒细胞转染Bcl-2基因对IGF-1分泌的影响

选用正在产蛋的罗曼鸡,取体积排序第一（F1）和第四（F4）的卵泡,分离颗粒细胞层细胞。采用脂质体介导方法将来源于F1和F4卵泡的颗粒细胞用PBS（对照）、空载体或Bcl-2重组质粒处理,然后在不完全无血清培养基（不添加胰岛素）中培养48和96h,用流式细胞术检测Bcl-2蛋白表达,用放射免疫测定技术检测IGF-1的含量。结果发现,转染Bcl-2重组质粒组的Bcl-2蛋白表达量和IGF-1分泌量均多于其他各组。分析来源于不同卵泡期卵泡颗粒细胞的分泌功能,发现随时间的增加F1细胞IGF-1分泌量减少,而F4的IGF-1分泌量基本不变。结果表明,在鸡卵泡颗粒细胞中转染的Bcl-2基因具有表达功能,表达的蛋白具有调节鸡卵泡颗粒细胞分泌IGF-1的作用;鸡卵泡颗粒细胞IGF-1的分泌还受鸡卵泡的大小和颗粒细胞在体外培养时间的影响。     

Vitamin D deficiency inhibits pancreatic secretion of insulin

The effects of a vitamin D deficiency on insulin and glucagon release was determined in the isolated perfused rat pancreas by radioimmunoassay of the secreted proteins. During a 30-minute period of perfusion with glucose and arginine, pancreases from vitamin D-deficient rats exhibited a 48 percent reduction in insulin secretion compared to that for pancreases from vitamin D-deficient rats that had been replenished with vitamin D. Vitamin D status had no effect on pancreatic glucagon secretion. This result, along with the previously demonstrated presence in the pancreas of a vitamin D-dependent calcium-binding protein and cytosol receptor for the hormonal form of vitamin D, 1,25-dihydroxyvitamin D3, indicates an important role for vitamin D in the endocrine functioning of the pancreas.     

Spatial coupling of mTOR and autophagy augments secretory phenotypes

Protein synthesis and autophagic degradation are regulated in an opposite manner by mammalian target of rapamycin (mTOR), whereas under certain conditions it would be beneficial if they occurred in unison to handle rapid protein turnover. We observed a distinct cellular compartment at the trans side of the Golgi apparatus, the TOR-autophagy spatial coupling compartment (TASCC), where (auto)lysosomes and mTOR accumulated during Ras-induced senescence. mTOR recruitment to the TASCC was amino acid- and Rag guanosine triphosphatase-dependent, and disruption of mTOR localization to the TASCC suppressed interleukin-6/8 synthesis. TASCC formation was observed during macrophage differentiation and in glomerular podocytes; both displayed increased protein secretion. The spatial coupling of cells' catabolic and anabolic machinery could augment their respective functions and facilitate the mass synthesis of secretory proteins.     

Antiallergic drug cromolyn may inhibit histamine secretion by regulating phosphorylation of a mast cell protein

Cromolyn inhibited histamine release from mast cells that was induced by a classic secretagogue and correspondingly increased incorporation of radioactive phosphate into a 78,000-dalton protein. These effects on histamine secretion and on protein phosphorylation were rapid in onset and both showed tachyphylaxis. Cromolyn may therefore act by altering the phosphorylation of a protein involved in the regulation of secretion.     

A role for the phagosome in cytokine secretion

Membrane traffic in activated macrophages is required for two critical events in innate immunity: proinflammatory cytokine secretion and phagocytosis of pathogens. We found a joint trafficking pathway linking both actions, which may economize membrane transport and augment the immune response. Tumor necrosis factor alpha (TNFalpha) is trafficked from the Golgi to the recycling endosome (RE), where vesicle-associated membrane protein 3 mediates its delivery to the cell surface at the site of phagocytic cup formation. Fusion of the RE at the cup simultaneously allows rapid release of TNFalpha and expands the membrane for phagocytosis.     

After insulin binds

Three recent advances pertinent to the mechanism of insulin action include (i) the discovery that the insulin receptor is an insulin-dependent protein tyrosine kinase, functionally related to certain growth factor receptors and oncogene-encoded proteins, (ii) the molecular cloning of the insulin proreceptor complementary DNA, and (iii) evidence that the protein tyrosine kinase activity of the receptor is essential for insulin action. Efforts are now focusing on the physiological substrates for the receptor kinase. Experience to date suggests that they will be rare proteins whose phosphorylation in intact cells may be transient. The advantages of attempting to dissect the initial biochemical pathway of insulin action include the wealth of information about the metabolic consequences of insulin action and the potential for genetic analysis in Drosophila and in man.     

小麦连体叶片高效瞬时表达体系的构建

分别以洋葱表皮和生长7d的小麦连体叶片为材料,采用HeliosTM基因枪将35S-sGFP-TYG-NOS(pUC19)外源基因导入植物细胞使其瞬时表达,摸索出一整套适合于小麦连体叶片高效瞬时表达体系的各项参数,包括:氦气压力、金粒子直径、PVP浓度、每次轰击的质粒DNA以及金粉用量等。并指出选用合适的质粒DNA浓度和多片小麦叶片同时轰击可有效提高转化效率。     

Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice

Medical applications of nanotechnology typically focus on drug delivery and biosensors. Here, we combine nanotechnology and bioengineering to demonstrate that nanoparticles can be used to remotely regulate protein production in vivo. We decorated a modified temperature-sensitive channel, TRPV1, with antibody-coated iron oxide nanoparticles that are heated in a low-frequency magnetic field. When local temperature rises, TRPV1 gates calcium to stimulate synthesis and release of bioengineered insulin driven by a Ca(2+)-sensitive promoter. Studying tumor xenografts expressing the bioengineered insulin gene, we show that exposure to radio waves stimulates insulin release from the tumors and lowers blood glucose in mice. We further show that cells can be engineered to synthesize genetically encoded ferritin nanoparticles and inducibly release insulin. These approaches provide a platform for using nanotechnology to activate cells.     

印楝素对min6细胞增殖及胰岛素分泌的影响

【目的】研究印楝素对min6细胞增殖、葡萄糖摄取及胰岛素分泌的影响,并探讨其作用机制。【方法】不同浓度印楝素处理min6细胞48 h,检测细胞增殖量。在5.5和25.0 mmol·L~(-1)葡萄糖条件下,检测印楝素处理细胞的葡萄糖摄取水平,胰岛素ELISA检测试剂盒检测细胞胰岛素的分泌。【结果】与对照组相比,在5.5和25.0mmol·L~(-1)葡萄糖条件下,印楝素均表现促进细胞增殖活性。印楝素处理下,与25.0 mmol·L~(-1)葡萄糖条件相比,5.5 mmol·L~(-1)葡萄糖表现出更显著地促进葡萄糖摄取和胰岛素分泌的作用。【结论】印楝素可能通过调控葡萄糖水平影响胰岛素的分泌。     

Selective pancreatic enzyme secretion due to a new peptide called chymodenin

Chymodenin, a peptide newly isolated from porcine duodenum, elicited a rapid threefold increase in secretion of chymotrypsinogen while increasing secrelion of total protein by only, about 40 percent; lipase secretion was unaffected. The pancreas appears able, under chymodenin stimulation, to rapidly alter the transport of an individual enzyme as opposed to producing en masse secretion of enzyme.     

Insulin-stimulated release of lipoprotein lipase by metabolism of its phosphatidylinositol anchor

Lipoprotein lipase (LPL) plays a critical role in the metabolism of plasma lipoproteins. In 3T3-L1 adipocytes, insulin elicits the rapid release of LPL through mechanisms that are independent of energy metabolism and protein synthesis. Some of the metabolic actions of insulin may be mediated by the activation of a specific phospholipase that hydrolyzes a glycosyl phosphatidylinositol (PI) molecule. The insulin-sensitive glycosyl-PI is structurally similar to the glycolipid membrane anchor of a number of proteins. LPL appears to be anchored to the 3T3-L1 cell surface by glycosyl-PI, and its rapid release by insulin may be due to activation of a glycosyl-PI-specific phospholipase C.     

家蚕五龄第1天与第4天后部丝腺蛋白质双向电泳图谱比较

 【目的】家蚕后部丝腺是合成分泌占蚕丝总量75%～80%丝素蛋白的器官，通过后部丝腺蛋白的研究，有利于阐明家蚕分泌丝素蛋白及蚕茧优质、高产的机理。【方法】采用蛋白质双向电泳和图像分析技术，研究了家蚕不同品种五龄第1天和第4天后部丝腺细胞的蛋白质组成变化。【结果】发现各个品种五龄第1天和第4天后部丝腺细胞的蛋白质组成存在差异，但蛋白质水平的差异，远远小于从EST分析得出的基因表达水平的差异；不同家蚕品种，从五龄第1天到第4天，后部丝腺细胞的蛋白质组成的变化规律各不相同。【结论】暗示了家蚕丝素分泌的过程可能受到多种蛋白的调控，不同的品种，在调控位点及调控蛋白上存在着一定的差异，从而导致了不同品种家蚕后部丝腺细胞在分泌丝素能力上的差异。     

Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Abeta42 by inhibiting Rho

A subset of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to preferentially reduce the secretion of the highly amyloidogenic, 42-residue amyloid-beta peptide Abeta42. We found that Rho and its effector, Rho-associated kinase, preferentially regulated the amount of Abeta42 produced in vitro and that only those NSAIDs effective as Rho inhibitors lowered Abeta42. Administration of Y-27632, a selective Rock inhibitor, also preferentially lowered brain levels of Abeta42 in a transgenic mouse model of Alzheimer's disease. Thus, the Rho-Rock pathway may regulate amyloid precursor protein processing, and a subset of NSAIDs can reduce Abeta42 through inhibition of Rho activity.     

Quantitative mass spectrometry identifies insulin signaling targets in C. elegans

DAF-2, an insulin receptor-like protein, regulates metabolism, development, and aging in Caenorhabditis elegans. In a quantitative proteomic study, we identified 86 proteins that were more or less abundant in long-lived daf-2 mutant worms than in wild-type worms. Genetic studies on a subset of these proteins indicated that they act in one or more processes regulated by DAF-2, including entry into the dauer developmental stage and aging. In particular, we discovered a compensatory mechanism activated in response to reduced DAF-2 signaling, which involves the protein phosphatase calcineurin.     

Autophagy as a regulated pathway of cellular degradation

Macroautophagy is a dynamic process involving the rearrangement of subcellular membranes to sequester cytoplasm and organelles for delivery to the lysosome or vacuole where the sequestered cargo is degraded and recycled. This process takes place in all eukaryotic cells. It is highly regulated through the action of various kinases, phosphatases, and guanosine triphosphatases (GTPases). The core protein machinery that is necessary to drive formation and consumption of intermediates in the macroautophagy pathway includes a ubiquitin-like protein conjugation system and a protein complex that directs membrane docking and fusion at the lysosome or vacuole. Macroautophagy plays an important role in developmental processes, human disease, and cellular response to nutrient deprivation.     

A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels

Several studies have shown that healthy individuals with fasting plasma glucose (FPG) levels at the high end of the normal range have an increased risk of mortality. To identify genetic determinants that contribute to interindividual variation in FPG, we tested 392,935 single-nucleotide polymorphisms (SNPs) in 654 normoglycemic participants for association with FPG, and we replicated the most strongly associated SNP (rs560887, P = 4 x 10(-7)) in 9353 participants. SNP rs560887 maps to intron 3 of the G6PC2 gene, which encodes glucose-6-phosphatase catalytic subunit-related protein (also known as IGRP), a protein selectively expressed in pancreatic islets. This SNP was associated with FPG (linear regression coefficient beta = -0.06 millimoles per liter per A allele, combined P = 4 x 10(-23)) and with pancreatic beta cell function (Homa-B model, combined P = 3 x 10(-13)) in three populations; however, it was not associated with type 2 diabetes risk. We speculate that G6PC2 regulates FPG by modulating the set point for glucose-stimulated insulin secretion in pancreatic beta cells.