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.     

Serotonin Inhibits Acetylcholine Release from Rat Striatum Slices: Evidence for a Presynaptic Receptor-Mediated Effect

Rat brain striatum slices were incubated with [3H]choline, perfused with a physiological buffer, and stimulated by perfusion with a K+-enriched buffer for 2 min. The tritium overflow evoked by K+ was decreased by 5-hydroxytryptamine (serotonin, 5-HT) (maximal inhibition 10(-6) M). This effect of 5-HT was mimicked by several agonists (5-methoxytryptamine, N,N-dimethyl-tryptamine, bufotenin) and blocked by serotonergic antagonists (methiothepin, methysergide, cinanserin) but not by haloperidol; methiothepin and methysergide alone slightly increased the K+-evoked overflow of tritium (3H). Inhibition of the tritium release by 5-HT was not suppressed in the presence of tetrodotoxin (TTX) (10(-6) M). These results suggest that 5-HT tonically inhibits acetylcholine (ACh) release from striatal cholinergic neurons by acting on a presynaptic receptor localized on cholinergic terminals.     

Times for recovery from cold-torpor in the Queensland fruit fly Dacus tryoni: the relation to temperature during and after chilling

Recovery time after experience of a given minimum temperature below torpor threshold is related to the value of that minimum, the length of time spent at that minimum, and the temperature prevailing during the recovery period above torpor threshold. A model can predict recovery time for flies experiencing a given temperature fluctuation if the length of time spent at the minimum is expressed as a proportion of LE₅₀ at that minimum.The model has applications in defining the optimal protocol for chilling insects for use in the Sterile Insect Release Method. The model was confirmed by experiments showing that it is likely that flies will recover from non-lethal frosts before ant predators become active.

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Résumé Le temps de récupération après avoir subi une température minimal située au-dessous du seuil d'engourdissement dépend de la valeur de ce minimum, du temps passé à ce minimum, et de la température au-dessus du seuil d'engourdissement pendant la période de récupération. Un modèle mathématique permet d'estimer le temps de récupération après avoir subi une chute de température déterminée, en fonction du temps passé au minimum thermique exprimé comme une fraction du LE₅₀ (temps nécessaire pour tuer 50% des mouches) à ce minimum.Ce modèle s'est trouvé étayé par des observations montrant qu'il est probable que les mouches se remettent des gelées sublétales avant la reprise d'activité des fourmis prédatrices. Ce modèle peut être utilisé pour définir les conditions optimales de refroidissement des insectes utilisés lors de la libération d'individus stériles.

     

Vesicle Shrinking and Enlargement Play Opposing Roles in the Release of Exocytotic Contents

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Low serum interleukin-6 levels as a predictive marker of recurrence in patients with hepatitis B virus related hepatocellular carcinoma who underwent curative treatment

BackgroundWe aimed to investigate the use of novel serum biomarkers for predicting the recurrence and survival of patients with hepatitis B virus (HBV)-related early hepatocellular carcinoma (HCC) after hepatic resection or radiofrequency ablation (RFA).MethodsOne hundred and five patients with HBV-related HCC, who fulfilled the Milan criteria without vascular invasion and underwent hepatic resection or RFA, were followed-up for a median duration of 52 months. Pretreatment serum concentrations of 16 cytokines including interleukin-6 (IL-6) were measured by using a Luminex 200 system. The measured serum cytokines and several clinical factors were analyzed retrospectively.ResultsUnivariate analysis showed that patients with lower pretreatment serum levels of IL-10, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α had significantly shorter disease-free survival (DFS) than those with higher levels. Multivariate analysis revealed that a low serum IL-6 level (⩽33.00 pg/mL; hazard ratio [HR] = 5.39; 95% confidence interval [CI] = 1.27–22.93; P = 0.022), low platelet count (<100 × 10⁹/L; HR = 2.23; 95% CI = 1.28–3.89; P = 0.005), and low serum albumin level (⩽3.5 g/L; HR = 2.26; 95% CI = 1.28–3.97; P = 0.005) had a negative prognostic impact on DFS. In the analysis for overall survival, a low serum platelet level (<100 × 10⁹/L; HR = 2.80; 95% CI = 1.31–5.99; P = 0.008) and multiple tumor (⩾2; HR = 4.05; 95% CI = 1.56–10.48; P = 0.004) showed a negative prognostic impact on the overall survival.ConclusionA low serum IL-6 level is, in addition to low platelet count and low serum albumin level, an independent prognostic factor for DFS in patients with HBV-related early HCC who underwent hepatic resection or RFA with curative intention.     

Intracellular calcium release mediated by two muscarinic receptor subtypes

Four subtypes of muscarinic acetylcholine receptor (mAChR) were stably expressed in neuroblastoma-glioma hybrid cells (NG108-15). By combining fluorescent indicator dye (fura-2) studies with electrophysiological measurements it is shown that stimulation of mAChR I and mAChR III readily leads to release of calcium from intracellular stores and to associated conductance changes, whereas stimulation of mAChR II and mAChR IV exerts no such effect. Dose-response curves describing the amplitude or the delay of the calcium rise induced by acetylcholine suggest that the apparent affinity of mAChR III for its agonist is higher by about one order of magnitude than that of mAChR I. Ionic substitution experiments and current fluctuation analysis indicate that calcium activates a K⁺-specific conductance of ‘small’ single-channel amplitude similar to the SK type [1]. Furthermore, an outward current (M current) suppressed by activation of mAChR I and mAChR III has a single-channel amplitude corresponding to a conductance of approximately 3 pS.