Altered insulin and glucagon secretion in perfused ethionine-treated rat pancreases

The endocrine secretory function of rat pancreases in which pancreatitis had been induced by feeding rats a 0.5% ethionine diet was investigated. Despite loss of 50% of exocrine tissue and widespread destruction of acinar structure, pancreatic insulin and glucagon contents and 4-h fasting plasma insulin levels in vivo did not differ significantly from those of food-restricted, weight-matched controls. Plasma glucose concentrations (fasting and after oral glucose) were significantly lower than control. In isolated, perfused ethionine-treated pancreases secretin failed to stimulate insulin secretion, whereas basal insulin secretion and insulin responses to glucose, arginine, gastric inhibitory polypeptide, vasoactive intestinal peptide (VIP), and somatostatin were similar to those of controls. Basal glucagon secretion was elevated in ethionine-treated pancreases, and glucagon outputs in response to arginine, VIP, and somatostatin showed a consistent trend toward higher levels than those of controls. These findings demonstrate that ethionine-induced pancreatitis selectively impairs islet secretory function. These effects may be due to damage to islet cell membranes by exocrine enzymes and/or a direct pathogenic action of ethionine on the islets.     

硒化角叉菜胶对大鼠心脏氧反常的作用

在离体大鼠心脏氧反常模型上,硒化角叉菜胶27mg/L(含硒0.3mg/L)可明显降低复氧时的室颤发生率(P<0.05)和静息张力(p<0.01)。以自旋捕捉技术(DMPO为捕捉剂)ESR谱仪检测氧反常心肌产生的自由基,可检出羟自由基(·OH)和碳中心自由基,分别与DMPO形成的自旋加合物,其中[DMPO-OH]·的相对峰强化比为1∶2∶2∶1,波谱参数aN=aH=15.01G;[DMPO-R]·的aN=16.25G,aH=23.25G。而硒化角叉菜胶有清除·OH以外的自由基的作用。     

Kinetics of pentose permeation in the perfused rat heart

1. The fractional permeation of heart cell water by L-arabinose and D-xylose after a standard period of perfusion is less the higher the extracellular pentose concentration.2. At any given pentose concentration the kinetics of permeation are consistent with passive diffusion through the cytoplasm or with transport across the cell membrane by a saturable carrier.3. The concentration dependence of permeation is inconsistent with passive diffusion.4. The kinetics of L-arabinose permeation are consistent with a carrier having V(max) = 2.2 m-mole/l. extracellular water per min and a half-saturation concentration [K] of 0.5 x 10(-4)M. The corresponding figures for D-xylose are V(max) = 1.4, [K] = 1.6 x 10(-4)M.     

Compartmentation of glycolysis and glycogenolysis in the perfused rat heart

Developing methods that can detect compartmentation of metabolic pathways in intact tissues may be important for understanding energy demand and supply. In this study, we investigated compartmentation of glycolysis and glycogenolysis in the isolated perfused rat heart using (13)C NMR isotopomer analysis. Rat hearts previously depleted of myocardial glycogen were perfused with 5.5 mm [U-(13)C]glucose plus 50 mU/mL insulin until newly synthesized glycogen recovered to new steady-state levels ( approximately 60% of pre-depleted values). After a short wash-out period, the perfusate glucose was then switched to [1-(13)C]glucose, and glycolysis and glycogenolysis were stimulated by addition of glucagon (1 microg/ml). A (13)C NMR multiplet analysis of the methyl resonance of lactate provided an estimate of pyruvate derived from glucose vs glycogen while a multiplet analysis of the C4 resonance of glutamate provided an estimate of acetyl-CoA derived from glycolytic pyruvate vs glycogenolytic pyruvate. These two indices were not equivalent and their difference was further magnified in the presence of insulin during the stimulation phase. These combined observations are consistent with functional compartmentation of glycolytic and glycogenolytic enzymes that allows pyruvate generated by these two processes to be distinguished at the level of lactate and acetyl-CoA.     

Distribution of adenine nucleotides in the perfused rat heart.

A computer technique for determination of the distribution of adenine nucleotides among compartmented, protonated, and metal-chelated species has been developed for the perfused rat heart. This procedure requires knowledge of tissue levels of creatine, creatine phosphate, ATP, ADP, and AMP and the glycolytic and respiration rates. The method is applicable to any physiological state of the organ and has been applied to transient behavior in aerobic, anoxic, and ischemic hearts. The results suggest that ADP uptake and ATP export by mitochondria are normally linked and equal in rate during aerobic metabolism or short-term anoxia but become separate and unequal during ischemia, so that mitochondrial adenine nucleotides, primarily AMP, accumulate.     

Functional and biochemical effects of a K+-ionophore on the isolated perfused rat heart

Valinomycin, a K⁺-specific ionophore, influenced function and metabolism of isolated, perfused rat hearts in a dose-dependent fashion. At a concentration of 0.05 μg ml^-1 in perfusion fluid a 50% reduction of heart rate (HR) and a 90% reduction in max dP/dt were observed. These effects were paralleled by a substantial decrease of myocardial energy charge from about 0.80 to 0.20. A 2.5 fold increase in tissue lactate concentration indicated an increased rate of glycolytic activity. Low ATP combined with high ADP and AMP levels as found in these valinomycin-treated hearts is known to promote phosphofructokinase activity and may explain the elevated lactate levels. A significant increase in the concentrations of adenosine, IMP and inosine was observed as well.