Improvement of gastric motility with gastric electrical stimulation in STZ-induced diabetic rats

AIMS: The aims of this study were to observe whether gastric motility was impaired in streptozotocin (STZ)-induced diabetic rats and whether gastric electrical stimulation was able to restore the impaired motility. METHODS: Ten control rats and 30 STZ-induced diabetic rats were used in this study. Gastric slow waves were recorded at baseline and 0, 1, 2, 3 and 4 weeks after the injection of STZ or vehicle. Gastric emptying with (long or short pulses) or without gastric electrical stimulation was measured 6 weeks after STZ injection in a group of 10 diabetic rats each. RESULTS: (1) STZ injection resulted in hyperglycemia and weight loss. (2) Gastric motility was impaired in the diabetic rats. The percentage of normal slow waves was progressively reduced 2 weeks after STZ injection. Compared with the control rats, gastric emptying in the diabetic rats was significantly delayed 6 weeks after STZ injection (60 +/- 3 vs. 79 +/- 2%, p < 0.02). (3) Gastric electrical stimulation with either long or short pulses accelerated gastric emptying in the diabetic rats. (4) Gastric electrical stimulation with long but not short pulses was capable of normalizing gastric dysrhythmia in the diabetic rats. CONCLUSION: Our data show that gastric motility is impaired in STZ-induced diabetic rats as reflected by a progressive reduction in the percentage of normal gastric slow waves and delayed gastric emptying. Moreover, here we show that gastric electrical stimulation normalizes delayed gastric emptying in diabetic rats and this normalization is not attributed to the effect of gastric electrical stimulation on gastric slow waves.     

Continuous inhibition of excessive polyol pathway flux in peripheral nerves by aldose reductase inhibitor fidarestat leads to improvement of diabetic neuropathy.

We investigated the effects of three aldose reductase (AR) inhibitors, fidarestat, epalrestat and zenarestat, on the slowing of sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), and minimal F-wave latency prolongation in streptozotocin (STZ)-induced diabetic rats. Two weeks after STZ injection, SNCV and MNCV in the diabetic rats were significantly slower than in normal rats. Fidarestat (0.25-2 mg/kg/day), epalrestat (48 to 96 mg/kg/day) or zenarestat (10-40 mg/kg/day) was administered orally for the following 2 weeks, and SNCV, MNCV and F-wave latency were measured 3 h after final administration. Significant prolongation of minimal F-wave latency, as well as slowing of SNCV and MNCV, was found in the untreated diabetic rats 4 weeks after STZ injection. At a dose of 0.5 mg/kg/day or more fidarestat showed significant effects on these nervous dysfunctions, effects that were more potent than those shown by the other inhibitors. Furthermore, following the 2-week administration of fidarestat (1 mg/kg/day), epalrestat (48 mg/kg/day) or zenarestat (20 mg/kg/day), which began 2 weeks after STZ injection, sorbitol content in the sciatic nerve, produced by AR, a rate-limiting enzyme in the polyol pathway, was determined at 3, 8, 12, and 24 h after final administration. At each point in time, sorbitol content in the untreated diabetic rats was much higher than that in the normal control rats. Fidarestat suppressed sorbitol accumulation remarkably and continuously until 24 h after administration. On the other hand, the inhibitory effect by zenarestat declined in a time-dependent manner, and epalrestat did not decrease sorbitol content. Therefore, these results suggest that continuous inhibition of increased polyol pathway flux can improve diabetic neuropathy more potently.     

Correlation between gastric emptying time and both plasma gastrin and pancreatic polypeptide in streptozotocin diabetic dogs

Correlation between gastric emptying time and both plasma gastrin and pancreatic polypeptide (PP) levels after meal was studied in 9 normal and 5 streptozotocin (STZ) diabetic dogs. Moreover, the effects of exogenous insulin at doses of 0.2 and 0.4 U/kg on gastric emptying and plasma hormone levels were also studied in STZ diabetic dogs. The time required to reach the peak of plasma acetaminophen level, which is the indirect indicator of gastric emptying rate, was significantly delayed in STZ diabetic dogs than in control dogs. Plasma gastrin response was delayed slightly in STZ diabetic dogs, but the plasma levels were not significantly different between the two groups. Plasma PP levels both in the basal and after postprandial state were significantly higher in STZ dogs than in normal dogs. Infusion of insulin did not affect plasma levels of acetaminophen and gastrin, while it produced a dose-dependent suppression of postprandial PP rise in STZ diabetic dogs. The foregoing data indicate that high level of plasma PP observed in STZ dogs did not correlate with gastric emptying but with insulin deficiency.     

Effects of streptozotocin-induced diabetes on glucose transport in skeletal muscle

Female Sprague-Dawley rats were injected with streptozotocin (45 mg/kg) to induce mild diabetes (glucose, greater than 13 mM). Half of the animals received daily insulin injections to reduce hyperglycemia. After 10 weeks, sarcolemmal membranes were isolated from hindlimb muscles to study glucose transport, and the number of glucose transporters was assessed by cytochalasin-beta binding. Both glucose transport (19.2 +/- 1.6 vs. 31.93 +/- 3.29 pmol/mg protein.15 sec) and cytochalasin-beta binding (3.06 +/- 0.28 vs. 6.14 +/- 0.59 pmol/mg protein) were significantly (P less than 0.05) reduced in the diabetic untreated rats compared to control values. Daily insulin injections restored both (P less than 0.05) basal transport (33.22 +/- 3.62 pmol/mg protein.15 sec) and cytochalasin-beta binding (5.52 +/- 0.66 pmol/mg protein) to control levels. Maximum insulin stimulation (1 U/kg, iv) significantly increased (P less than 0.05) both glucose transport (30.18 +/- 3.76 vs. 96.48 +/- 4.21 pmol/mg protein.15 sec) and cytochalasin-beta binding (4.38 +/- 0.29 vs. 9.40 +/- 0.42 pmol/mg protein) in the untreated diabetic and control rats. However, the stimulation in the untreated diabetic rats only reached basal control levels, which was significantly (P less than 0.05) below the insulin-stimulated value for the controls. In the rats receiving daily insulin injections, maximum insulin stimulation increased (P less than 0.05) both glucose transport (58.67 +/- 15.24 pmol/mg protein.15 sec) and cytochalasin-beta binding (6.4 +/- 0.7 pmol/mg protein), but both transport and binding were significantly (P less than 0.05) below insulin-stimulated values for the control rats. These data show that insulin deficiency adversely affected the glucose transport system in skeletal muscle. Both basal and maximum insulin-stimulated transport and the number of transport molecules were reduced. Daily insulin treatment corrected some of the defects, but maximum insulin stimulation was still significantly below values for control animals.     

Omega-3 polyunsaturated fatty acids inhibit the accumulation of PAS-positive material in the myocardium of STZ-diabetic wistar rats

This study was conducted to investigate the effect of Omega-3 PUFA on streptozotocin (STZ)-induced diabetic cardiomyopathy in wistar rats. After 4 weeks of STZ (60 mg/kg, i.v.) administration, the diabetic animals were randomly divided into two groups: Diabetic control and Omega-3 PUFA treated diabetic rats. Omega-3 PUFA (0.5 ml/kg) was administered to the latter group for 10 weeks. Age matched normal rats served as Normal controls. During the study, plasma glucose, glycosylated hemoglobin, plasma cholesterol, LDL and HDL cholesterol, triglyerides were evaluated in all the groups. Omega-3 PUFA treatment did not normalise but instead blunted the effect of diabetes with regards to the above parameters significantly (P<0.01). At the end of the experiment, morphometric and histochemical studies were performed on heart and myocardial enzyme markers were studied. In the diabetic control group, diabetic cardiomyopathy was characerised by elevated CPK (DC 110+/-8.85 vs. NC 39+/-5.83) and morphological changes in heart. Gravimetric ratios showed increased heart-to-body weight ratio in diabetic control over normal control group. (DC 3.38+/-0.05 vs. NC 2.48+/-0.03). Histochemical evidence showed increased accumulation of PAS-positive material in myocardial interstitium (++++). The Omega-3 PUFA treatment blunted all these adverse effects of diabetes on heart significantly (P<0.001). However, further studies are warranted to elucidate the mechanism by which Omega-3 PUFA decreases the accumulation of PAS-positive material in diabetic myocardium.     

Ileal brake failure in streptozotocin-induced diabetic rat

BACKGROUND: Diabetes mellitus frequently alters gastrointestinal function, but the pathophysiology of the diabetic gut has not been fully elucidated. Our aim was to characterize the enterogastric modulation of gastric emptying in an experimental model of diabetic rat and to determine the putative consequences of impaired regulation on glycaemic control. METHODS: Studies were performed in streptozotozin-induced diabetic and control groups of male Sprague-Dawley rats. In rats fitted with chronic ileal cannulae, gastric emptying of a peptide meal was measured during ileal infusion of either lipids (ileal brake) or saline. The influence of the ileal brake mechanism on blood glucose levels after oral administration of a glucose solution was also evaluated. RESULTS: Diabetic rats exhibited a precipitous gastric emptying (80% +/- 3% versus 57% +/- 3% in controls; P < 0.05). Ileal lipids delayed gastric emptying in control (38 +/- 4%; P < 0.05 versus ileal saline) but not in diabetic animals (77 +/- 5%; N.S. versus ileal saline). As the ileal brake contributes to the management of postprandial blood glucose levels (114 +/- 4.9 mg/dL after ileal lipids versus 134 +/- 7.8 mg/dL after ileal saline in control rats; P < 0.05), the failure of this mechanism in diabetic rats worsens glycaemic control after feeding (455 +/- 20.4 mg/dL after ileal lipids versus 399 +/- 8.7 mg/dL after ileal saline; P < 0.05). CONCLUSION: Experimental diabetes impairs the ileal brake mechanism and disturbs gastric emptying. These abnormalities may contribute to difficult glycaemic control.     

Undisturbed water gastric emptying in patients of stomach cancer

BACKGROUND/AIMS: Gastric cancer is an infiltrative disease involving deep layers of the stomach. It is of interest whether the stomach motility in gastric cancer patients may be altered. We employed a homemade applied potential tomographic system to study the features of water gastric emptying in gastric cancer patients. METHODOLOGY: Twelve electrodes were placed in a circular array around the upper abdomen of studied subjects. After drinking 500 mL of test water, paired electrodes injected an electrical current and another 9 paired electrodes recorded signals. This procedure was processed in a rotated order for 50 min while the serial changes in altered resistivity were constructed to display water gastric emptying curve. Before surgery, 27 histologically confirmed gastric cancer patients were enrolled to measure their gastric emptying parameters including half emptying time (T1/2) and area under the curve (AUC). Consequently, tumor parameters were obtained from their resected specimens. In addition, 28 healthy controls were recruited to compare water gastric emptying. RESULTS: The half emptying times of gastric cancer patients and controls were 15.51 +/- 2.21 (SE) and 16.82 +/- 2.13 min, respectively (NS). While their measured areas under the curve were also comparable (1719.5 +/- 169.4 vs. 1896.0 +/- 143.6 arbitrary unit, NS). Regarding with various patient factors to influence water gastric emptying among gastric cancer patients, those patients presenting nausea (T1/2: 8.3 +/- 1.44 vs. 18.5 +/- 2.8 min, P<0.05) or free of regional lymph node metastasis (9.98 +/- 2.53 vs. 22.7 +/- 3.84 min, P<0.05) had a rapid water gastric emptying. Other demographic and tumor characteristics including gender, age, smoking, body size, serum levels of tumor markers, cancer location/size, invasion layer, Helicobacter pylori colonization and histological subtype did not influence water gastric emptying. CONCLUSIONS: Water gastric emptying in non-obstructive gastric cancer patients is mainly undisturbed. However, some obvious dyspeptic symptom or tumor nature appears leading to a rapid water gastric emptying.     

Evaluation of gastric emptying and motility in diabetic gastroparesis with magnetic resonance imaging: effects of cisapride

OBJECTIVE: The motor mechanisms that underlie both slow gastric emptying in diabetic gastroparesis and its acceleration by cisapride are poorly understood. We have recently shown that magnetic resonance imaging (MRI) allows concurrent evaluation of both gastric emptying and regional gastric motility. METHODS: Emptying and motility were measured in eight diabetic patients with previously demonstrated delayed gastric emptying using a rapid MRI technique during oral administration of cisapride and placebo. Studies were performed in a double blind fashion and each patient acted as his own control. Subjects were studied supine for 120 min in a 1.5 Tesla MRI scanner after ingestion of 500 ml of 10% Intralipid. Gastric emptying corrected for the volume of secretions was determined every 15 min using transaxial scans. Each transaxial scan was followed by 120 coronal scans at 1 s intervals. Coronal scans were angled to provide simultaneous imaging of the proximal and distal stomach. MRI studies were also performed in seven diabetic patients with normal emptying who served as disease controls. RESULTS: Emptying was slower in the gastroparetic patients (t(1/2): 124 +/- 10 min) compared to patients with normal emptying (81 +/- 9 min, p < 0.05). Cisapride accelerated gastric emptying (74 +/- 5 vs 124 +/- 10 min) in patients with gastroparesis. The contraction amplitudes in the proximal stomach of gastroparetic patients were increased during cisapride treatment (17.2% +/- 1.8% vs 13.2% +/- 0.6%; p < 0.02), whereas antral contraction frequency, amplitude, and velocity were unchanged. CONCLUSIONS: We conclude that cisapride-induced acceleration of liquid gastric emptying in diabetic gastroparesis does not appear to result from changes in antral contractility, but may be related to changes in proximal gastric tone or gastric outlet resistance.     

Autonomic neuropathy in streptozotocin diabetic rats: effect of acetyl-L-carnitine

The present study was designed to characterize cardiac autonomic neuropathy in streptozotocin-induced (45 mg/kg i.v.) diabetic rat by analysis of heart rate variability (HRV), and to assess, in this model, the effects of treatment with acetyl-L-carnitine (ALC). Heart rate was reduced in diabetic rats (332+/-22 vs. 411+/-35 beat per min; P<0.0001). This bradycardia was partly reversed with ALC (369+/-52 beat per min; P<0.05 vs. untreated). Both time- and frequency-domain parameters of HRV were significantly reduced in diabetic rats. The reduction of spectral power was around 50% at high frequencies and about 70% at low frequencies, suggesting a decrease of parasympathetic activity. Low/high frequency ratio was significantly decreased in diabetic rats suggesting decreased sympathetic tone, while nonlinear analysis indicated a reduction of the chaotic complexity of heart rate dynamics in diabetic rats. Standard deviation of heart rate in ALC-treated rats was significantly higher than in untreated diabetic rats (P<0.0001). ALC counteracts the reduction of the power spectrum observed in diabetic animals (P<0.0005) normalizing the spectra profile. ALC restored chaotic complexity of heart rate dynamics. These results on the whole indicate that both sympathetic and parasympathetic cardiac tone were reduced significantly in diabetic rats and that ALC treatment prevents the development of autonomic neuropathy in streptozotocin-induced diabetes in rats.     

Insulin resistance in rats with non-insulin-dependent diabetes induced by neonatal (5 days) streptozotocin: evidence for reversal following phlorizin treatment

We have examined the effect of chronic (4 weeks) phlorizin treatment (osmotic minipumps) on tissue sensitivity to insulin in adult female rats with non-insulin-dependent diabetes (NIDD) induced by streptozotocin (STZ) (80 mg/kg) administered 5 days after birth. Insulin sensitivity was assessed with the euglycemic-hyperinsulinemic clamp technique in anesthetized animals. In the untreated diabetic rats, the basal glucose production (GP) and glucose utilization (GU) were increased (P less than .001), and both the liver and peripheral tissues showed insulin resistance. In the phlorizin-treated diabetic rats, postabsorptive plasma glucose levels were decreased and remained stable during the last 3 weeks of the treatment (142 +/- 3 mg/dL as compared with 308 +/- 19 in the untreated diabetic rats and 119 +/- 3 in the phlorizin-control rats); their percent glycosylated hemoglobin values returned to normal (3.2 +/- 0.2 as compared with 5.8 +/- 0.4 in the untreated diabetic rats); their basal plasma insulin levels (55 +/- 5 microU/mL as compared with 52 +/- 3 in the untreated diabetic rats and 130 +/- 10 in the phlorizin-control rats), their in vivo glucose-induced insulin secretion, and their pancreatic insulin content were kept unchanged. In the phlorizin-treated diabetic rats, the basal GP and GU were normalized. Following a submaximal or maximal hyperinsulinemia, GP was normally suppressed and GU normally enhanced. Phlorizin treatment in the control rats did not affect any of the above parameters. These data demonstrate that correction of hyperglycemia with phlorizin normalizes insulin action on glucose metabolism by the liver and peripheral tissues in this diabetic model. This is in line with the proposal that hyperglycemia per se can lead to the development of insulin resistance.     

胰高血糖素样肽-1对糖尿病大鼠胃排空的非受体通路的影响

目的探讨室旁核(Paraventricular nucleus,PVN)内胰高血糖素样肽-1(Glucagon-like pepetide-1,GLP-1)是否存在非受体通路参与糖尿病大鼠胃排空的中枢调节。方法 40只雄性Wistar大鼠随机分为正常对照组(NC组)、糖尿病组(DM组)、GLP-1(7-36)干预组(GLP组)、Exendin(9-39)联合GLP-1干预组(E-G组)及Exendin(9-39)干预组(Exendin组)。制备糖尿病大鼠模型,PVN埋置套管并给予GLP-1(7-36)或Exendin(9-39)等药物,2周后甲基纤维素-酚红溶液测胃排空;实时荧光定量分析法检测PVN区GLP-1受体(GLP-1R)mRNA表达情况。结果注射STZ 2周后,GLP组及E-G组胃排空率较DM组、Exendin组均明显降低(P均0.05),但高于NC组(P0.05);GLP组及E-G组的下丘脑GLP-1R mRNA表达较DM组、NC组、Exendin组均明显增高(P均0.05)。GLP组胃排空率和空腹血糖较E-G组降低(P0.05);下丘脑GLP-1R mRNA表达GLP组与E-G组比较差异无统计学意义(P0.05)。结论室旁核注射GLP-1可减缓糖尿病大鼠早期的胃排空,推测GLP-1影响胃排空的中枢作用机制除促进GLP-1受体表达增加外,非受体作用通路亦发挥重要作用。     

十八味诃子利尿丸对大鼠2型糖尿病性胃轻瘫的作用

目的探讨十八味诃子利尿丸对大鼠2型糖尿病性胃轻瘫的一般状况、血糖浓度、胃排空率、小肠推进率及胃窦部组织的影响。方法24只大鼠随机分为模型组、藏药组和空白组,每组8只。模型组和藏药组采用高脂饲料联合链脲佐菌素建立2型糖尿病胃轻瘫大鼠模型。藏药组连续3 w隔天灌胃予十八味诃子利尿丸;模型组和空白组同时进行灌胃予等量生理盐水。监测大鼠建模成功后和灌药结束后24 h饮水摄食、血糖浓度及体重的变化;计算灌药后大鼠胃排空率和小肠推进率;光镜下观察大鼠胃窦部的病理形态学改变。结果藏药组与模型组比较,灌药后24 h饮水摄食减少、血糖浓度下降、胃排空率及小肠推进率增加,差异具有统计学意义(P<0.05);而体重无明显差异(P>0.05);胃黏膜炎症缓解,细胞胞质疏松化减轻。结论十八味诃子利尿丸对大鼠2型糖尿病性胃轻瘫可能具有一定的保护作用。     

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study

OBJECTIVE: The stomach is the main target organ for bariatric surgery, but no medical treatment has been developed to increase satiety and decrease food intake via gastric pathways. The aim of our study was to investigate whether or not the intraparietogastric administration of botulinum toxin A (BTX), able to modify the motility patterns of the stomach, could be useful for treatment of obesity. DESIGN: Double blind controlled study. SUBJECTS: Twenty-four morbidly obese patients (mean weight (s.e.m.) 116.1+/-4.89 kg, mean body mass index (BMI) 43.6+/-1.09 kg/m(2)) were blindly randomized to receive 200 IU BTX or placebo into the antrum and fundus of the stomach by intraparietal endoscopic administration. MEASUREMENTS: We evaluated weight loss, BMI changes, satiety score, the maximal gastric capacity for liquids and the gastric emptying time (octanoic acid breath test). RESULTS: The two groups were homogeneous for anthropometric characteristics. Eight weeks after treatment, BTX patients had significantly higher weight loss (11+/-1.09 vs 5.7+/-1.1 kg, P<0.001) and BMI reduction (4+/-0.36 vs 2+/-0.58 kg/m(2), P<0.001) and a higher satiety score on a visual analogic scale (7.63+/-0.38 vs 4.72+/-0.44, P<0.001) than controls. Furthermore, BTX patients showed a significantly greater reduction in maximal gastric capacity for liquids (266.6+/-48 vs 139+/-31, P<0.001) and a greater prolongation in gastric emptying time (+18.93+/-8 vs -2.2+/-6.9 min, P<0.05). No significant side effects or neurophysiologic changes were found. CONCLUSIONS: Topical intragastric BTX was effective in reducing food intake and body weight in morbidly obese patients.     

Gastric neuropeptides and gastric motor abnormality in streptozotocin-induced diabetic rats: observation for four weeks after streptozotocin

Alterations of gastric calcitonin gene-related peptide and substance P content and gastric emptying in early stages of streptozotocin-induced diabetic rats were investigated. Diabetes was induced by intravenous injection of streptozotocin (50 mg/kg) in male Wistar rats. Gastric emptying of phenol red solution and calcitonin gene-related peptide and substance P content of gastric walls, measured by radioimmunoassay, was assessed two and four weeks after streptozotocin injection. Gastric emptying two weeks after streptozotocin was delayed (32 ± 9%) and that four weeks after was enhanced (73 ± 2%) compared with nondiabetic control rats (50 ± 3%). Calcitonin gene-related peptide content of the gastric antrum and corpus was increased two weeks after and decreased four weeks after streptozotocin, while gastric substance P content was not changed at any time in diabetic rats. Insulin treatment reversed alterations of gastric emptying and calcitonin gene-related peptide content. The delayed gastric emptying in two-week diabetic rats was reversed by CGRP antagonist and the enhanced gastric emptying in four-week diabetic rats was reversed by CGRP pretreatment. These results suggest a possible relationship between gastric calcitonin gene-related peptide and abnormal gastric motility in diabetic state.     

Hypoglycemic effect of Du-zhong (Eucommia ulmoides Oliv.) leaves in streptozotocin-induced diabetic rats

The current study investigated whether Du-zhong (Eucommia ulmoides Oliv.) leaves could improve the hyperglycemia in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into a non-diabetic group (NDM), diabetic group (DM), diabetic group supplemented with powdered Du-zhong leaves (DM-PDZ) and diabetic group supplemented with a water extract of the powdered Du-zhong leaves (DM-WDZ). Diabetes was induced by injecting STZ (70 mg/kg B.W., i.p.). The powdered Du-zhong leaves or its powdered water extract was add to a standard diet based on 1% dried Du-zhong leaves (1 g PDZ/100 g diet and 0.187 g WDZ/100 g diet, respectively) for 3 weeks. Body weight was significantly higher in both types of Du-zhong leaves supplemented groups than in the DM group. The blood glucose levels were significantly lower in the DM-PDZ and DM-WDZ groups than in the DM group (20.05+/-0.88 and 18.96+/-1.23 mmol/l versus 24.42+/-1.07 mmol/l, P<0.05), whereas the plasma insulin and C-peptide levels were significantly higher in the PDZ and WDZ supplemented groups than in the DM group (7.45+/-0.27 and 7.62+/-0.69 microl U/ml versus 3.75+/-0.27 microl U/ml for the plasma insulin, and 224.52+/-14.6 and 239.76+/-15.52 pmol/l versus 166.5+/-10.4 pmol/l for the plasma C-peptide, respectively, P<0.05). The supplementation of PDZ and WDZ also resulted in lower plasma urea nitrogen levels compared to the DM group. Du-zhong leaves supplement seemed to be helpful to preserve the normal histological appearance of pancreatic islets as well as to preserve insulin-positive beta-cells but it did not reverse the effect of STZ to a great extent. Accordingly, the reduction in plasma glucose by the powdered Du-zhong leaves and its water extract is quite small but significant, nevertheless, this was occurred with simultaneous the increase in plasma insulin and C-peptide. They improved hyperglycemia and seemingly enhance the function of pancreatic beta-cells in STZ-induced diabetic rats.     

Epalrestat prevents the decrease in gastric mucosal blood flow and protects the gastric mucosa in streptozotocin diabetic rats

We have recently reported that steady-state gastric mucosal blood flow (GMBF) is decreased in streptozotocin (STZ) diabetic rats, and that their GMBF response to burn-stress is impaired, probably via a nitric oxide (NO)-mediated mechanism. Accordingly, this study was designed to investigate the relation of aldose reductase (AR) and NO synthase to the regulation of GMBF during chronic hyperglycemia. STZ rats were treated with or without chronic oral administration of an AR inhibitor, epalrestat (EPA) and/or an NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME). GMBF was measured by laser-Doppler velocimetry (LDV). In the STZ rats, GMBF after a 24-h fasting period was decreased significantly 4 weeks after the onset of diabetes and this was accompanied by an increase in the gastric ulcer index (UI) (a measure of the length of gastric erosions and ulcers). Chronic oral administration of EPA to the STZ rats dose-dependently inhibited the increased UI and the decreased GMBF after the fasting stress, whereas chronic oral administration of L-NAME further increased the UI and further decreased the GMBF. EPA administered in combination with L-NAME to the STZ rats reduced the effects of L-NAME, but the effects did not reach significance. These results suggest that EPA protects the gastric mucosa of diabetic rats, by preventing the decrease in GMBF that is, at least in part, caused by NO-related mechanisms. (Received Mar. 3, 1998; accepted Aug. 28, 1998)     

Induced-hyperglycemia attenuates erythromycin-induced acceleration of hypertonic liquid-phase gastric emptying in type-I diabetic patients

BACKGROUND: Erythromycin has been found to be a gastrointestinal prokinetic agent of hypertonic liquids, while acute hyperglycemia has been associated with delayed gastric emptying in diabetic patients. AIM: To investigate whether hyperglycemia, per se, reduces gastric motility during erythromycin-induced acceleration on gastric emptying of hypertonic liquids in diabetic patients. METHODS: In 12 type-I diabetic patients following a hypertonic radiolabeled liquid meal, gastric emptying was measured scintigraphically during normoglycemia (5-8.9 mmol/l glucose) or hyperglycemia induced by intravenous (16-19 mmol/l) glucose infusion. The tests were performed on 4 separate days in random order after administering either placebo or 200 mg i.v. erythromycin. RESULTS: In the hyperglycemic state compared to normoglycemia, the gastric emptying of the hypertonic liquid was reduced after placebo or erythromycin administration. The lag-phase duration (17.8+/-5.5 and 7.8+/-4.5 vs. 10.8+/-3.4 and 3.7+/-2.5 min, respectively, p<0.001), the overall gastric emptying time of the half meal (52.8+/-13 and 24.9+/-5.5 vs. 42.5+/-10.5 min and 16.6+/-6 min, respectively, p<0.001) and the retained percentage of liquid meal in the stomach at 60 and 100 min postprandially (p<0.001) were significantly increased. CONCLUSIONS: The erythromycin-induced acceleration on gastric emptying of hypertonic liquids in diabetic patients is related to the plasma glucose level. The induced hyperglycemia reduces the erythromycin-induced acceleration of liquid-phase gastric emptying, decreasing the overall gastric emptying rate. In spite of the inhibitory effect of induced hyperglycemia on the gastric emptying of hypertonic liquids, erythromycin is still able to accelerate the emptying rate and could prove to be a useful prokinetic agent under hyperglycemic conditions.     

钒酸盐对糖尿病大鼠骨骼肌GLUT4基因表达的影响

观察钒酸欠对ＳＴＺ糖尿病大鼠糖代谢的影响地这一作用产生的机理进行了探讨。以０．５ｍｇ／ｍｌ钒酸钠溶液作为饮用水治疗三周后，糖尿病治疗组的血糖低于非治疗组３７．５％，但仍较正常组高。而骨骼肌中ＧＬＵＴ４ｍＲＮＡ含量较非治疗组高７３．８％，但仍代于正常组。     

Combination treatment of vitamin C and desferrioxamine suppresses glomerular superoxide and prostaglandin E production in diabetic rats

AIMS: Increased oxidative stress may contribute to the development of diabetic nephropathy. Conversely, it has been proposed that enhanced glomerular production of prostaglandin E(2) (PGE(2)) may be the cause of glomerular hyperfiltration in streptozotocin (STZ)-induced diabetic rats. As the role of superoxide anion (O(2-)) production in early diabetic nephropathy is not fully understood, we investigated the effect of vitamin C and desferrioxamine treatment on glomerular O(2-) and PGE(2) production in diabetic rats. METHODS: STZ-induced diabetic rats were given drinking water containing 1 g/l of vitamin C and desferrioxamine for 10 days, and glomerular O(2-) production, glomerular PGE(2) synthesis and creatinine clearance were examined. RESULTS: Glomerular O(2-) production increased in untreated diabetic rats compared to non-diabetic controls (142.2 +/- 12.4 vs. 65.4 +/- 3.6 counts/mg protein/min). Treatment with vitamin C and desferrioxamine significantly decreased glomerular O(2-) production (93.7 +/- 6.7 counts/mg protein/min). Glomerular PGE(2) synthesis and creatinine clearance were significantly increased in untreated diabetic rats compared to controls and PGE(2) synthesis was reduced and creatinine clearance tended to decrease by the treatment. CONCLUSIONS: Our results demonstrated that vitamin C and desferrioxamine suppressed the enhanced glomerular O(2-) production with subsequent decrease in PGE(2) production. Antioxidant therapy may be beneficial in preventing the development of diabetic nephropathy.     

Symptomatic,radionuclide and therapeutic assessment of chronic idiopathic dyspepsia

Twenty-eight patients with chronic idiopathic dyspepsia defined by the presence of chronic unexplained symptoms suggestive of gastric stasis and directly related to food ingestion were included in this prospective study. Gastric emptying of the liquid and solid phases of a meal was quantified by a dual-isotope method, and symptoms were evaluated by a diary and a visual analog scale. Delay in gastric emptying was evidenced in 59% of the dyspeptic patients; it occurred with liquids in more cases than solids. Quantitative and qualitative evaluation of symptoms was of no practical value in predicting the presence of objective stasis. The dyspeptic patients were included in a double-blind randomized controlled trial of cisapride, a new gastrokinetic drug devoid of central antiemetic effects. After six weeks of cisapride treatment, all patients with initially abnormal gastric emptying rates for liquids, and all but one for solids returned to normal ranges, and significant differences between cisapride and placebo groups were observed for half emptying times of both solids (136 +/- 16 min vs 227 +/- 32 min; P less than 0.02) and liquids (61 +/- 4 min vs 132 +/- 37 min; P less than 0.01). Cisapride also significantly improved dyspeptic symptom scores at weeks 3 and 6 of treatment as compared to those measured before treatment. Nevertheless, the decrease in global diary score was significantly higher than that seen with placebo at week 3 (-16 +/- 6 vs -1 +/- 9; P less than 0.05), but not at week 6 (-18 +/- 5 vs -10 +/- 8).(ABSTRACT TRUNCATED AT 250 WORDS)