Diabetes alters contraction-induced mitogen activated protein kinase activation in the rat soleus and plantaris.

The prescription of anaerobic exercise has recently been advocated for the management of diabetes; however exercise-induced signaling in diabetic muscle remains largely unexplored. Evidence from exercise studies in nondiabetics suggests that the extracellular-signal-regulated kinases (Erk1/2), p38, and c-JUN NH2-terminal kinase (Jnk) mitogen-activated protein kinases (MAPKs) are important regulators of muscle adaptation. Here, we compare the basal and the in situ contraction-induced phosphorylation of Erk1/2- p38- and Jnk-MAPK and their downstream targets (p90rsk and MAPKAP-K2) in the plantaris and soleus muscles of normal and obese (fa/fa) Zucker rats. Compared to lean animals, the time course and magnitude of Erk1/2, p90rsk and p38 phosphorylation to a single bout of contractile stimuli were greater in the plantaris of obese animals. Jnk phosphorylation in response to contractile stimuli was muscle-type dependent with greater increases in the plantaris than the soleus. These results suggest that diabetes alters intramuscular signaling processes in response to a contractile stimulus.

[Pharmacological studies on the clathrate compound of mobenzoxamine with beta-cyclodextrin. (I). Effects on the digestive system].

Effects of the clathrate compound of mobenzoxamine (MBX) with beta-cyclodextrin (MBX-CD), a new gastro-intestinal function modulator, on the digestive system were studied in comparison with those of metoclopramide, domperidone and trimebutine. MBX-CD showed inhibitory effects that were approximately 1/4 times as potent as metoclopramide on both apomorphine- and copper sulfate-induced emesis and about 1/40 times as potent as domperidone on apomorphine-induced emesis in dogs. In rats, MBX-CD enhanced gastric emptying as potently as metoclopramide, and only MBX-CD showed a clear amelioration of the delayed gastric emptying induced by BaCl2. Similarly, only MBX-CD showed an ameliorative effect on small intestinal transport accelerated by BaCl2 in mice. Though both MBX and trimebutine inhibited spontaneous contractions of the isolated guinea pig stomach and rabbit intestine, it seemed that the properties of these effects were different from those of papaverine. On isolated guinea pig ileum, MBX inhibited contractions induced by various agonists equally to or more potently than trimebutine or papaverine. The results suggest that MBX-CD or MBX acts extensively on the gastro-intestinal system for the reason that it has not only the respective properties of the gastro-intestinal function modulators used as the standards, but also its own characteristic effects.

[Studies on defensive factors of experimental ulcers (2). Increasing action of aceglutamide aluminum on defensive factors in acetic acid ulcers of rats (author's transl)].

Severe ulcers were produced in rats by injections of 20% acetic acid in a volume of 0.05 ml into the subserosal layer of two portions in the corpus, and the effects of aceglutamide aluminum on hexosamine, sialic acid, uronic acid and hydroxyproline contents of the mucosa and stroma in the ulcerated regions were compared with the effects of L-glutamine. When aceglutamide aluminum (1,000 mg/kg x 2/day) was orally administered for 4 consecutive days beginning the day of the operation, this drug inhibited the ulcer index and the perforations in ulcerated regions by 18 and 66%, respectively. In addition, the drug remarkably increased the total amounts (microgram/ulcer areas/rat) of hexosamine, sialic acid, and uronic acid in the mucosa of ulcerated regions. It was notable than with the sialic acid contents, an increase in the concentration (microgram/100 mg dry tissue) was also observed. On the other hand, in the stroma of ulcerated regions, the contents of those components containing hydroxyproline were little affected by this drug. Following daily oral administration for 14 consecutive days, aceglutamide aluminum (1,000 mg/kg x 2/day) brought about more potent effects than those following the 4 days administrations, and this drug showed a 37% inhibition of the ulcer index and a complete inhibition of the perforations. Moreover, the drug pronouncedly increased both total amounts and concentrations of hexosamine, sialic acid, and uronic acid in the mucosa in the ulcerated portions. Of these components, the increment of the sialic acid content was the greatest. In the stroma of ulcerated portions, total amounts and concentrations of those components containing hydroxyproline were significantly increased by this drug, although the increase in the stroma were less than those in the mucosa. These effects of aceglutamide aluminum were far more potent than those of L-glutamine at the same dose. From the above results, aceglutamide aluminum may accelerate ulcer repair by potentiating defensive factors through the increases of components forming the mucus and granuloma in ulcerated tissues.

[Pharmacological studies on experimental nephritic rats (13). The development and aggravation of nephritis due to the repeated administration of liquoid (author's transl)].

In order to elucidate the role of blood coagulation system in the development and aggravation of glomerulonephritis, liquoid (Liq) was repeatedly administered to normal or nephritic rats. When Liq 10 mg/kg was given i.v. daily X 22 to normal rats (group I), the urinary excretions of protein and N-acetyl-beta-glucosaminidase and urea nitrogen content did not significantly change as compared with those in the normal control group. In rats given Liq 10 mg/kg i.v. either every 3 days X 8 (group III) or every day X 22 (group IV) from the 15th day after the i.v. administration of anti-rat glomerular basement membrane rabbit serum (AGS) [0.5 ml/150g body weight], these biochemical parameters were not significantly different from those of nephritic control rats given AGS only (group II). The deposits of fibrin or fibrinoids in glomeruli of groups I, II, III and IV, examined by a fluorescence antibody technique were evident in 2, 2, 8 and 10, respectively, out of 10 rats in each group, although the degree of deposition was slight. Under light microscopy, the adhesion between the glomerular capillary wall and Bowman's capsule, hypercellularity, crescent formation and hyalinization were demonstrated in a part of glomeruli, even in group I. concerning the influence of Liq in nephritic rats, the most prominent glomerular change was hyalinization. While in group II the hyalinization was evident in only 17% of glomeruli, in groups III and IV the hyalinization was 41 and 55%, respectively. Although no significant difference was seen between groups II and III regarding other glomerular changes except for hypercellularity, these changes in group IV increased as compared with those in group II. However, hypercellularity was less in groups III and IV than in group II. A slight occlusion of the glomerular capillary lumen was observed, even in group I. In nephritic groups, the degree of the capillary lumen occlusion in group IV was greater than that in group II. From these results, the acceleration of intraglomerular blood coagulation is considered to be a major factor in the development and aggravation of glomerulonephritis.