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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pancreata of streptozotocin-induced diabetic rats were examined to determine whether the pancreatic tissue content of catecholamines is altered after the onset of diabetes. Experimental diabetes was induced by intraperitoneal injection of streptozotocin (60 mg/kg body weight). Four weeks after the induction of diabetes, pancreatic tissue fragments were taken from the tail end of the pancreas and processed for catecholamine content using the high-performance liquid chromatography method. Immunohistochemical analysis showed that the pancreata of diabetic rats contained more tyrosine hydroxylase-positive nerves compared with controls. Pancreatic noradrenaline content, expressed as the mean +/- SD, was significantly (p < 0.03) greater in diabetic rats (54+/-11.74 pg x mL(-1) x mg tissue(-1)) compared with normal, sex- and age-matched control rats (37.54+/-1.18 pg x mL(-1) x mg tissue(-1)). Similarly, the adrenaline content in diabetic rat pancreatic tissue (102.69+/-20.24 pg x mL(-1) mg tissue(-1)) was markedly greater (p < 0.003) compared with sex- and age-matched controls (35+/-9.23 pg x mL(-1) x mg tissue(-1)). In contrast, 5-hydroxyindole acetic acid decreased significantly (p < 0.0002) in diabetic pancreatic tissue (13.41+/-0.87 pg x mL(-1) x mg tissue(-1)) compared with controls (80.72+/-1.46 pg x mL(-1) x mg tissue(-1)). The plasma levels of these catecholamines also increased slightly but not significantly in diabetic rats compared with controls. These results suggest that diabetes is associated with increased noradrenaline and adrenaline and decreased 5-hydroxyindole acetic acid pancreatic tissue levels. These disturbances in catecholamine metabolism may play a role in the pathogenesis of the acute and chronic complications of diabetes mellitus.
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PMID:Streptozotocin-Induced diabetes mellitus is associated with increased pancreatic tissue levels of noradrenaline and adrenaline in the rat. 1129 35

The cardiovascular response to an aerobic cycloergometer exercise test (ACET, 15 min at 60 W, 60 rpm) and the maximally attainable muscle power output, assessed by a stair climbing test (SCT), were evaluated in 60 obese patients (41 females and 19 males; age: 18-68 yr; body mass index, BMI: 40.8+/-4.8 kg/m2) before and after a 3-week body mass reduction (BMR) program, entailing integrated energy-restricted diet (1200-1500 kcal/day), low-grade aerobic exercise conditioning and individual and/or group psychological therapy. The daily conditioning protocol (5 days/week) consisted of: 1) 30 min of indoor jogging and dynamic aerobic standing and floor exercises performed with arms and legs, under the guidance of a therapist; 2) 30 min of cycloergometer exercise at 60 W; and/or 3) 4-km outdoor leisure walking on flat terrain. Three weeks of BMR program induced a significant weight loss (-4.5 %; p<0.001), a reduction of systolic (-11+/-14 mmHg, -7.3%,p<0.001) and diastolic (-7+/-9 mmHg, -7.3%,p<0.001) resting arterial blood pressure, as well as a reduction of heart rate at rest (-18.6%,p<0.001), during ACET (-11.3%,p<0.001) and 5 min thereafter (-14.8%,p<0.001). The subjective rating of perceived exertion in terms of breathlessness and general fatigue during ACET, scored on a 0-100 visual analogic scale, was significantly reduced (p<0.001) after BMR program. A 11.2% decrease in SCT time (p<0.001) was also observed, corresponding to a 9.6% increase (p<0.001) in average muscle power (W) and 14.6% increase (p<0.001) in specific muscle power (W.kg(-1)). In conclusion, a combination of energy restricted diet, low intensity aerobic exercise and psychological counselling appears to significantly improve both aerobic and anaerobic performance in morbidly obese subjects. Different factors (ie, reduction of body mass, shift in the balance between parasympathetic and sympathetic activity, a weight-loss dependent shift toward a more favourable region of the muscle power-velocity curve, acquisition of a certain degree of motor skillfulness during the conditioning program, improvement of self-esteem and motivation) might be responsible, alone or in combination, for these short-term positive effects of BMR program.
Diabetes Nutr Metab 2001 Feb
PMID:Aerobic and anaerobic performance before and after a short-term body mass reduction program in obese subjects. 1134 66

PURPOSE It has been proposed that a deficiency in the axonal transport of nerve growth factor (NGF) may have an important role in inducing diabetic neuropathy, which contributes to diabetic cystopathy. Therefore, in streptozotocin (Sigma Chemical Co., St. Louis, Missouri) induced diabetic rats we investigated the relationship of bladder function with NGF levels in the bladder and lumbosacral dorsal root ganglia, which contain afferent neurons innervating the bladder. MATERIALS AND METHODS At 6 and 12 weeks after the induction of diabetes with streptozotocin (65 mg./kg. intraperitoneally) the effects of diabetes on Adelta afferent fiber dependent, conscious voiding were evaluated by metabolic cage measurements and awake cystometry. The effects of diabetes on C-fiber mediated bladder nociceptive responses were also investigated by cystometry with intravesical instillation of 0.25% acetic acid in the rats under urethane anesthesia. NGF levels in the bladder and L6 to S1 dorsal root ganglia were measured by enzyme-linked immunosorbent assay 3, 6, 9 and 12 weeks after streptozotocin injection. RESULTS In diabetic rats NGF levels in the bladder and L6 to S1 dorsal root ganglia were significantly decreased 12 weeks after streptozotocin injection (p <0.01). In cystometry and metabolic cage studies bladder capacity and post-void residual volume were significantly increased 12 weeks after streptozotocin injection (p <0.01). Bladder nociceptive responses revealed by a reduction in inter-contraction intervals after acetic acid infusion were significantly decreased in a time dependent manner 12 weeks after streptozotocin injection.CONCLUSIONS Rats with streptozotocin induced diabetes mellitus showed a significant time dependent decrease in NGF levels in the bladder and L6 to S1 dorsal root ganglia that was associated with voiding dysfunction attributable to defects in Adelta and C-fiber bladder afferents. Therefore, reduced production of NGF in the bladder and/or impaired transport of NGF to L6 to S1 dorsal root ganglia, which contain bladder afferent neurons, may be an important mechanism inducing diabetic cystopathy.
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PMID:Diabetic cystopathy correlates with a long-term decrease in nerve growth factor levels in the bladder and lumbosacral dorsal root Ganglia. 1218 78

We have recently demonstrated that serotonin (5-HT) increases the production of type 4 collagen by cultured human mesangial cells. Here we examined the clinical effects of a 5-HT(A2) receptor antagonist whether it would prevent the development or progression of diabetic nephropathy. We compared the levels of 5-hydroxyindole-3-acetic acid (5-HIAA), the major metabolite of 5-HT, in 24-h urine samples of patients with type 2 diabetes (n=110) and normal subjects (n=40). We then investigated the effects of 24-month treatment with sarpogrelate hydrochloride, a 5-HT(A2) receptor antagonist, on urinary albumin level in 10 type 2 diabetics with microalbuminuria, compared with not treated control group. Urinary 5-HIAA in diabetic patients was significantly higher (3.44+/-1.43 mg/day) than in normal subjects (1.62+/-0.50 mg/day, P<0.001), and correlated significantly with hemoglobin A1c (r=0.56, P<0.001) and with fasting blood glucose (r=0.37, P<0.001). Sarpogrelate significantly reduced urinary albumin excretion level within 3 months of commencement of treatment (24.3+/-8.58 mg/g Cr, P<0.05), which was persistently seen during the treatment, while no such change was noted in the control group (32.2+/-13.4 mg/g Cr). Our study indicate that high levels of 5-HT in type 2 diabetics may be one of the underlying mechanisms of diabetic nephropathy, and that treatment with 5-HT(A2) receptor antagonists may reduce or inhibit the development of nephropathy.
Diabetes Res Clin Pract 2002 Nov
PMID:Sarpogrelate hydrochloride, a serotonin2A receptor antagonist, reduces albuminuria in diabetic patients with early-stage diabetic nephropathy. 1221 54

Starting from the known inhibitory activity of (3-benzoylpyrrol-1-yl)acetic acid (I) and (2-benzoylpyrrol-1-yl)acetic acid (II), a series of 3-aroyl and 2,4-bis-aroyl derivatives (54-75) were synthesized and tested for inhibition of aldose reductase, an enzyme involved in the appearance of diabetic complications. It was found that a number of the tested compounds exhibited considerable activity in the micromolar range. Important structural features for the potent compounds is the presence of substituents with relatively low Hammett sigma values and/or moieties which increase their overall aromatic area. The most active derivative was the [2,4-bis(4-methoxybenzoyl)pyrrol-1-yl]acetic acid (75), with potency favorably compared to known ARIs such as tolrestat, epalrestat, zopolrestat, and fidarestat. Four selected derivatives were also evaluated for their ability to interfere with the oxidative modification of serum albumin in an in vitro experimental glycation model of diabetes mellitus. All of them showed considerable activity, comparable to the known inhibitor trolox. Our results, taken together, indicate that compound 75 combines favorably two biological activities directly connected to a number of pathological conditions related to the chronic diabetes mellitus.
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PMID:Substituted pyrrol-1-ylacetic acids that combine aldose reductase enzyme inhibitory activity and ability to prevent the nonenzymatic irreversible modification of proteins from monosaccharides. 1254 Feb 41

Advanced glycation end products (AGE), formed by nonenzymatic Maillard reactions between carbohydrate and protein, contribute to the increase in chemical modification and crosslinking of tissue proteins with age. Acceleration of AGE formation in collagen during hyperglycemia, with resultant effects on vascular elasticity and basement membrane permeability, is implicated in the pathogenesis of diabetic complications. AGE-breakers, such as N-phenacylthiazolium (PTB) and N-phenacyl-4,5-dimethylthiazolium (PMT) halides, have been proposed as therapeutic agents for reversing the increase in protein crosslinking in aging and diabetes. We have confirmed that these compounds, as well as the AGE-inhibitor pyridoxamine (PM), cleave the model AGE crosslink, phenylpropanedione, and have studied the effects of these compounds in reversing the increased crosslinking of skin and tail collagen isolated from diabetic rats. Crosslinking of skin collagen, measured as the half-time for solubilization of collagen by pepsin in 0.5M acetic acid, was increased approximately 5-fold in diabetic, compared to nondiabetic rats. Crosslinking of tail tendon collagen, measured as insolubility in 0.05 N acetic acid, was increased approximately 10-fold. Collagen preparations were incubated in the presence or absence of AGE-breakers or PM in phosphate buffer, pH 7.4, for 24h at 37 degrees C. These treatments did not decrease the half-time for solubilization of diabetic skin collagen by pepsin or increase the acid solubility of diabetic tail tendon collagen. We conclude that, although AGE-breakers and PM cleave model crosslinks, they do not significantly cleave AGE crosslinks formed in vivo in skin collagen of diabetic rats.
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PMID:AGE-breakers cleave model compounds, but do not break Maillard crosslinks in skin and tail collagen from diabetic rats. 1264 66

We examined how diabetes affects the beta-adrenoceptor subtypes mediating relaxation of rat urinary bladder smooth muscle contracted with carbachol. The relaxant responses to isoproterenol were larger in muscles from rats 8 to 10 weeks after induction of diabetes with streptozotocin (80 mg/kg, i.p.) as compared to the control muscles. In contrast, forskolin-induced relaxations did not differ significantly in the control and diabetes groups. Propranolol (1 microM) abolished the diabetes-induced augmentation of relaxant responses to isoproterenol. The relaxant responses to T-0509 ((-)-(R)-1-(3,4-dihydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)-amino]ethanol hydrochloride), a beta(1)-adrenoceptor agonist, were small but significantly augmented by diabetes. On the other hand, diabetes did not change the relaxations produced by clenbuterol, a beta(2)-adrenoceptor agonist, and BRL37344 ((+/-)-(R*,R*)-(4-[2-([2-(3-chlorophenyl)-2-hydroxyethyl]amino)propyl]phenoxy)acetic acid), a beta(3)-adrenoceptor agonist. These results suggest that diabetes selectively augments the beta(1)-adrenoceptor-mediated relaxation of the rat urinary bladder smooth muscle.
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PMID:Augmentation of rat urinary bladder relaxation mediated by beta1-adrenoceptors in experimental diabetes. 1270 74

Gastric mucosa of diabetic rats is highly vulnerable to acute injury, but little is known about the influence of diabetic conditions on the healing of gastric ulcers. In this study, streptozotocin (70 mg/kg injected intraperitoneally) was used to induce diabetes mellitus in rats. Four weeks after streptozotocin injection, gastric ulcers were induced using the acetic acid method, and 10 days later, the healing rate and the gastric blood flow (GBF) were measured by planimetry and hydrogen (H(2))-gas clearance method, respectively. Six major groups of rats with gastric ulcers were used: (1) vehicle (saline); (2) streptozotocin alone; (3) insulin (4 IU/day intraperitoneally); (4) streptozotocin plus insulin; (5) pentoxifylline, an inhibitor of synthesis and release of tumor necrosis factor-alpha (TNF alpha); and (6) aspirin, a non-selective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and rofecoxib, the highly selective COX-2. In the diabetic rats, a significant delay in ulcer healing ( approximately by 300%), accompanied by a decrease in the gastric mucosal blood flow was observed. The prolongation of the healing in diabetic animals was associated with an increase in gastric mucosal expression and release of TNFalpha, interleukin-1 beta (IL-1 beta), suppression of the vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM-1) and the mucosal overexpression of heat shock protein 70 (HSP 70). Administration of insulin reversed the delay in ulcer healing and significantly decreased the expression of IL-1 beta and TNF-alpha, while producing the rise in the expression of VEGF and PECAM. Pentoxifylline, an inhibitor of TNF-alpha, which by itself accelerated ulcer healing in non-diabetic rats, counteracted the increase in the area of gastric ulcer induced by streptozotocin, raised significantly gastric blood flow and suppressed the plasma TNF-alpha levels. Aspirin and rofecoxib, that significantly suppressed the mucosal prostaglandin E(2) generation in ulcer area, delayed significantly the rate of ulcer healing and decreased the GBF at ulcer margin in non-diabetic rats, and these changes were significantly augmented in diabetic animals. We conclude that: (1) Experimental diabetes dramatically impairs ulcer healing, depending upon the increased release of proinflammatory cytokines and the attenuation of angiogenesis that can limit the ulcer healing effects of locally produced HSP 70 and TNF-alpha. (2) Insulin reversed this impairment of ulcer healing in diabetic rats, mainly due to the enhancement of angiogenesis and reduction in expression of cytokines in the ulcer area. (3) Classic non-steroidal anti-inflammatory drugs such as aspirin prolonged ulcer healing under diabetic conditions due to suppression of endogenous prostaglandins and the fall in the microcirculation at the ulcer margin and these effects were mimicked by selective, so called "safe" COX-2 inhibitor, rofecoxib, suggesting that both COX isoforms are important sources of prostaglandins that are essential in the ulcer healing in diabetes.
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PMID:Impaired gastric ulcer healing in diabetic rats: role of heat shock protein, growth factors, prostaglandins and proinflammatory cytokines. 1464 93

Vinegar is generally believed to be good for health. A mash consisting of 35% ethanolic extract from bitter melon malt vinegar-water (8:50:42) was subjected to further acetate fermentation and the resulting vinegar was converted to dried vinegar powder by spray drying after adsorption on dextrin, which was mixed with a commercial rat chow (CRF-1) in the ratio of 1:19 so as to prepare an experimental diet. Male 12-wk old rats of LETO and OLETF strains were fed this experimental diet in parallel with CRF-1 (control) and examined for respiratory quotient (RQ) and blood or plasma parameters associated with diabetes mellitus. Administration of the experimental diet increased daily food intake as well as daily energy expenditure in both strains. RQ significantly lessened in the vinegar diet-fed group of LETO strain, which was reflected not only in the increased energy consumption from fat but also in the decreased energy consumption from carbohydrate, while no significant difference was observed between both dietary groups of OLETF strain in this respect. The profiles of diurnal energy expenditure in both dietary groups of LETO strain exerted two peaks before lights-on and lights-off. Nevertheless, there was a clear difference between both dietary groups of OLETF strain: interestingly the reproduction of the two peaks became conspicuous in the vinegar diet-fed group despite the lack of such peaks in the control. As a consequence of blood or plasma inspection, it turned out that there was no change in HbA1c but a significant increase in plasma cholesterol in the vinegar diet-fed OLETF rats. From these results, a long-term administration of bitter melon malt vinegar can be expected to suppress a lowering of energy turnover inherent with aging and thereby improve anorexia rather than to bring about a preventive effect against the manifestation of NIDDM.
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PMID:Bitter melon malt vinegar increases daily energy turnover in rats. 1497 34

[1-(3,5-Difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone (6) was synthesized as a putative bioisostere of the known aldose reductase (AR) inhibitor (3-benzoylpyrrol-1-yl)acetic acid (I). It was found that 6 is approximately 5 times more potent as an in vitro inhibitor of AR than I, with an IC(50) value in the submicromolar range. Furthermore, 6 showed considerable activity in an in vitro experimental glycation model of diabetes mellitus. Our results support the notion that 6 might become a useful lead structure.
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PMID:[1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone as a bioisostere of a carboxylic acid aldose reductase inhibitor. 1511 13


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