The stimulus-secretion coupling of amino acid-induced insulin release metabolic interaction L-asparagine and L-leucine in pancreatic islets

1. Because L-asparagine augments insulin release evoked by L-leucine, the metabolism of these two amino acids was investigated in rat pancreatic islets. 2. L-Leucine inhibited the uptake and deamidation of L-asparagine, but failed to exert any obvious primary effect upon the further catabolism of aspartate derived from exogenous asparagine. 3. L-Asparagine augmented the oxidation of L-leucine, and effect possibly attributable to activaion of 2-ketoisocaproate dehydrogenase. 4. The association of L-asparagine and L-leucine exerted a sparing action on the utilization of endogenous amino acids, so that the integrated rate of nutrients oxidation was virtually identical in the sole presence of L-leucine and simultaneous presence of L-asparagine and L-leucine, respectively. 5. It is proposed that the enhancing action of L-asparagine upon insulin release evoked by L-leucine is attributable to an increased generation rate of cytosolic NADPH rather than any increase in nutrients oxidation.     

Protein arginine methylation promotes therapeutic resistance in human pancreatic cancer

Pancreatic cancer is a lethal disease with limited treatment options for cure. A high degree of intrinsic and acquired therapeutic resistance may result from cellular alterations in genes and proteins involved in drug transportation and metabolism, or from the influences of cancer microenvironment. Mechanistic basis for therapeutic resistance remains unclear and should profoundly impact our ability to understand pancreatic cancer pathogenesis and its effective clinical management. Recent evidences have indicated the importance of epigenetic changes in pancreatic cancer, including posttranslational modifications of proteins. We will review new knowledge on protein arginine methylation and its consequential contribution to therapeutic resistance of pancreatic cancer, underlying molecular mechanism, and clinical application of potential strategies of its reversal.     

Phylogenetic diversity is a better predictor of wetland community resistance to Alternanthera philoxeroides invasion than species richness

• Highly biodiversity communities have been shown to better resist plant invasions through complementarity effects. Species richness (SR) is a widely used biodiversity metric but lacks explanatory power when there are only a few species. Communities with low SR can have a wide variety of phylogenetic diversities (PD), which might allow for a better prediction of invasibility.
• We assessed the effect of diversity reduction of a wetland community assemblage typical of the Beijing area on biotic resistance to invasion of the exotic weed Alternanthera philoxeroides and compared the reduction in SR and PD in predicting community invasibility.
• The eight studied resident species performed similarly when grown alone and when grown in eight‐species communities together with the invasive A. philoxeroides. Variation partitioning showed that PD contributed more to variation in both A. philoxeroides traits and community indicators than SR. All A. philoxeroides traits and community indicators, except for evenness index, showed a linear relationship with PD. However, only stem length of A. philoxeroides differed between the one‐ and two‐species treatments, and the diversity index of the communities differed between the one‐ and two‐species treatments and between the one‐ and four‐species treatments.
• Our results showed that in natural or semi‐natural wetlands with relatively low SR, PD may be a better predictor of invasibility than SR. When designing management strategies for mitigating A. philoxeroides invasion, deliberately raising PD is expected to be more efficient than simply increasing species number.

     

Acute effects of Amomum villosum Lour. fruit extract on postprandial glycemia and insulin secretion: A single-blind,placebo-controlled,crossover study in healthy subjects

BackgroundAmomum villosum Lour., (Zingiberaceae) an herbaceous plant in the ginger family, has been used to treat various diseases. In a single-blind, randomized, crossover study, we assessed the postprandial blood insulin and blood glucose responses in healthy subjects (n = 40) after the Amomum villosum water extract (AVE) (5 g/person) or a placebo (5 g/person) consumption.MethodsDuring each treatment course, the healthy subject consumed a regular late afternoon meal, followed by fasting for 12 h, and arrived at the clinical study center the next morning. Blood insulin and blood glucose levels were assessed at 0, 30, 60, 90, and 120 min after AVE consumption. Between each treatment, the subjects accomplished one week of a washout period.ResultsThe AVE intake demonstrated a significant (67.26%) decline in postprandial blood glucose AUC_{0–120 min} (incremental area under the curve from 0 to 120 min) versus the placebo (P = 0.011). Furthermore, AVE reduced postprandial blood insulin AUC_{0–120 min} by 59.95% compared to the placebo group (P < 0.003), supporting the blood glucose results.ConclusionThis study revealed that AVE consumption significantly reduced postprandial insulin and glucose levels in healthy individuals, due in part to inhibition of α-glucosidase, and glucose transport.     

Cytoplasmic APE1 promotes resistance response in osteosarcoma patients with cisplatin treatment

Chemotherapy resistance has become a hold back and major clinical challenge in osteosarcoma cancer. The alteration and subcellular distribution of apurinic/apyrimidinic endonuclease 1 (APE1) has been reported to be involved in chemotherapy resistance in many cancers. Here, we report that the cytoplasmic distribution of APE1 plays a key role in the sensitivity of combination platinum chemotherapy in osteosarcoma. Interestingly, the prevalence of cisplatin-induced DNA damage and apoptosis in low cytoplasmic APE1 osteosarcoma cell lines was higher than in high expression of cytoplasmic APE1 cell lines. Overexpression of cytoplasmic APE1 protected the osteosarcoma cells from CDDP-induced apoptosis. In addition, clinical data also show that the level of cytoplasmic APE1 was negatively associated with sensitivity to combination chemotherapy of cisplatin in osteosarcoma patients. Our findings suggest that cytoplasmic APE1 plays a significant role in chemotherapy resistance. This role is a supplement to the extranuclear function of APE1, and cytoplasmic APE1 expression level could be a promising predictor of platinum treatment prognosis for osteosarcoma patients.     

An Aphid-Secreted Salivary Protease Activates Plant Defense in Phloem

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EXPERIMENTAL EVOLUTION OF RESISTANCE IN BRASSICA RAPA: CORRELATED RESPONSE OF TOLERANCE IN LINES SELECTED FOR GLUCOSINOLATE CONTENT

The evolutionary response of plant populations to selection for increased defense may be constrained by costs of defense. The purpose of this study was to investigate such constraints on the evolution of defense due to a cost of defense manifested as a trade-off between defense and tolerance. Variation in the response to artificial damage (tolerance) among lines of Brassica rapa that had been artificially selected for foliar glucosinolate content (defense) was examined. Leaf area was removed from replicates of three selection lines (high glucosinolates, control, and low glucosinolates) at three damage levels (0%, 20%, and 60% damage). An external cost of defense would result in a statistically significant selection line by damage treatment interaction, with those selected for high defense expressing less tolerance than those selected for low defense. Damage treatment had a significant overall effect on estimated total fitness, with fitness declining with increasing damage level. Further, selection line also had a significant overall effect on estimated total fitness, with low-defense selection lines having higher fitness compared to both control and high-defense selection lines. More importantly, a cost of defense in terms of tolerance was demonstrated by a significant selection line-by-damage treatment interaction. This interaction was in the direction to demonstrate a genetic trade-off between defense and tolerance, with low-defense selection lines decreasing estimated total fitness in response to damage less than both control and high-defense selection lines. Variation in tolerance among selection lines was due to the greater ability of low-defense lines to maintain fruit and seed production despite the presence of damage. In terms of tolerance, this cost of glucosinolate production in B. rapa could constrain the evolution of increased defense and, in so doing, maintain individuals within the population that are poorly defended yet tolerant.     

Dispersal capacity in the Mediterranean corn borer, Sesamia nonagrioides

Corn (Zea mays L.) borers are the primary target of Bacillus thuringiensis Berliner (Bt) transgenic maize. Management of corn borer resistance to Bt requires information on larval and adult dispersal capacities, a feature that is particularly unknown in Sesamia nonagrioides Lefèbvre (Lepidoptera: Noctuidae), the most damaging corn borer in Spain. Larval dispersal was studied over a 3 year period by infesting plants with egg masses and dissecting the neighbouring plants 7, 14, and 32 days later to measure larval dispersal at several ages. The number and age of larvae were recorded in the dissected plants. Only mature larvae dispersed in significant numbers; they moved at least to rows adjacent to those containing the infested plant, and down the row five plants. The percentage of larvae that dispersed from the infested plant was density‐dependent. Adult dispersal was studied with directional light and pheromone uni‐traps over 5 and 3 year periods, respectively. Directional light traps were placed in the margins between Bt and non‐Bt maize fields, half oriented towards each of the two kinds of maize field. Pheromone traps were placed in the Bt and non‐Bt fields at increasing distances (0–100 m) from the border. The numbers of males and females caught in directional light traps were not different in traps oriented towards Bt or non‐Bt fields, but the number of males caught in the third flight in Bt fields was lower than in non‐Bt fields. These results suggest that males from adjacent Bt and non‐Bt fields mate indiscriminately with females emerging in any of the two kinds of maize fields. However, male movement in the third flight may not be sufficient to randomly distribute males between the two fields.