Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RT6 is a glycosylphosphatidylinositol-linked protein found on the surface of mature rat T lymphocytes. Cells that express RT6 have an immunoregulatory function and modulate the expression of autoimmune diabetes mellitus in the BioBreeding rat. A homologue of the rat RT6 gene, designated Rt6, has been identified in the mouse, but expression of mouse Rt6 protein has not been documented. Rat RT6 is known to be a nicotinamide adenine dinucleotide (NAD+) glycohydrolase. We now report that rat RT6.2 and recombinant mouse Rt6 locus 1 proteins possess auto-ADP ribosylation activity. In addition, mouse Rt6 but not rat RT6, catalyzes the ADP ribosylation of exogenous acceptors such as histones. The ADP-ribosyl-protein bonds in auto-ADP-ribosylated rat RT6.2, auto-ADP-ribosylated mouse Rt6, and ADP-ribosylhistone synthesized by Rt6 were stable to HgCl2 and HCl, but labile to NH2OH, consistent with ADP ribosylarginine linkages. To determine if these enzymatic activities could affect the function of rat T cells, the effect of substrate availability on lymphocyte proliferation was examined. An inverse correlation was observed between NAD+ concentration in the medium and the ability of rat T cells to respond to anti-CD3, ConA, and PMA plus ionomycin. The data suggest that lymphocyte surface ADP ribosyltransferases could be involved in signaling and immunoregulatory processes.
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PMID:Rat RT6.2 and mouse Rt6 locus 1 are NAD+: arginine ADP ribosyltransferases with auto-ADP ribosylation activity. 866 96

1. The anti-obesity and anti-diabetic effects of mazindol were evaluated in obese diabetic yellow KK mice and C57Bl control mice. 2. The study compound was fed through a gastric tube at a rate of 1 or 2 mg/kg per day (0.01 mol/L HCl as control) for 2 weeks. The following parameters were compared in treated and control animals: bodyweight, food intake, white adipose tissue (WAT) weight, brown adipose tissue (BAT) weight and its thermogenesis, noradrenaline (NA) turnover, blood glucose and serum insulin levels and glucose transporter 4 (GLUT4). 3. Furthermore, bodyweight loss of mice pair-fed the same amount of food as the mazindol-treated mice for 2 weeks was measured. 4. Mazindol significantly decreased food intake and significantly increased guanosine-5'-diphosphate-binding in BAT mitochondria and NA turnover in BAT in both yellow KK and C57Bl groups. The amounts of WAT in subcutaneous, mesenteric and retroperitoneal regions and bodyweights were significantly decreased in both groups. Bodyweight loss in mice pair fed with the mazindol-treated groups was approximately 70% compared with that in the mazindol-treated groups. Furthermore, mazindol decreased the levels of blood glucose and serum insulin during the glucose overloading test in yellow KK mice, but it did not influence the GLUT4 protein concentration in WAT and muscle. 5. These observations suggest that mazindol possesses both an anti-obesity action, due to the inhibition of appetite as well as the activation of BAT thermogenesis via increased NA turnover in BAT, and an anti-diabetic action. Consequently, mazindol may be useful for the treatment of obesity as well as non-insulin-dependent diabetes mellitus in obese persons.
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PMID:Anti-obesity and anti-diabetic effects of mazindol in yellow KK mice: its activating effect on brown adipose tissue thermogenesis. 880 May 69

This study was designed to evaluate the percutaneous absorption of insulin in an attempt to develop an efficient transdermal therapeutic system (system) for the treatment of diabetes. First, the dissociation of porcine insulin existing mainly as hexamers was examined. Next, enhancement of the percutaneous absorption of the hormone was studied by the combined use of two or more kinds of enhancers which exert their enhancement effects by different mechanisms, or by preparing the liposomal formulation of insulin. Porcine insulin dissociated in 0.1 M glycine-HCl buffer (pH 4.0), probably to a dimer, this being demonstrated by the notable attenuation of the maxima at 221 and 274 nm of the circular dichroism (CD) spectra. Thus, 0.1 M (or partly 1 M) glycine-HCl buffer (pH 4.0) was selected for the preparation of all gel formulations. The in vivo absorption of insulin through Wistar rat skin was estimated by blood glucose level. System 3 containing liposomal insulin, D-limonen and taurocholate gave the greatest hypoglycemic response, out of the formulations used, with its response persisting over a 10 h period and resulting in the highest pharmacological availability (20.7 +/- 4.6%). The combination of n-octyl-beta-D-thioglucoside (OTG), cineol and deoxycholate (system 6) or D-limonen and OTG (system 5) also produced a high hypoglycemic effect. The in vitro penetration of insulin was investigated using system 5 and 6. The percutaneous penetration of insulin was demonstrated by an in vitro experiment, but was small in quantity. Our data present unambiguous evidence that this hydrophilic macromolecule was absorbed through the stratum corneum of rat skin under selected conditions.
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PMID:Dissociation of insulin oligomers and enhancement of percutaneous absorption of insulin. 887 14

This study evaluated the effects of treatment with an inhibitor of advanced glycation endproducts, aminoguanidine, on the development of albuminuria, mesangial expansion and glomerular basement membrane (GBM) thickening in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which we found to be an excellent model of non insulin-dependent diabetes mellitus (NIDDM), for its very close similarity to human NIDDM. OLETF rats were randomized into a non-treatment diabetic group (D-group, n = 5) and an aminoguanidine-treated group (AG-group, n = 5). The AG-group was given 100 mg/dl aminoguanidine HCl in free drinking water. Treatment was started at 16 weeks of age. We measured body weight, plasma glucose, total cholesterol, triglycerides and the urinary albumin excretion (UAE) rate before and after treatment at regular intervals. At 56 weeks of age, we measured serum advanced glycation endproducts (AGE), mesangial expansion and glomerular basement membrane. There were no significant differences in pre-treatment body weight, plasma glucose and UAE between the D-group and the AG-group. Likewise, after treatment there were no significant differences in body weight, plasma glucose, total cholesterol, triglycerides and immunoreactive insulin. Significant differences were, however, noted in serum AGE (63.2 +/- 3.5 and 51.8 +/- 3.0 U AGE/ml, P < 0.05), UAE (203.6 +/- 37.7 and 89.8 +/- 18.6 mg/day, P < 0.05), fractional mesangial volume (21.3 +/- 1.7 and 16.7 +/- 0.8%, P < 0.05) and GBM thickness (453 +/- 17 and 366 +/- 50 nm, P < 0.05) between the D-group and the AG-group. Our results suggest that aminoguanidine inhibits the AGE formation and the development of diabetic nephropathy in OLETF rats.
Diabetes Res Clin Pract 1997 Jan
PMID:Effects of aminoguanidine on serum advanced glycation endproducts, urinary albilmin excretion, mesangial expansion, and glomerular basement membrane thickening in Otsuka Long-Evans Tokushima fatty rats. 906 63

We examined the influence of diabetes on the healing of HCI-induced gastric lesions and the healing promoting effect of basic fibroblast growth factor (bFGF) on these lesions under diabetic conditions induced in rats by streptozotocin (70 mg/kg, i.p.). The experiments were performed using 2-wk streptozocin-diabetic rats with blood glucose levels of >300 mg/dl. After 18 hr fasting, these animals were given 1 ml of 0.6 N HCl by gavage, and 1 hr later they were fed normally before being killed on various days after HCI treatment. Recombinant human basic fibroblast growth factor (acid resistant recombinant human basic fibroblast growth factor mutein CS-23: 10 to 1000 ng/kg x 2, p.o.) or insulin (4 U/rat x 1, s.c.) was given 5 days after HCl treatment. Gastric lesions induced by HCI healed to quiescent state within 5 days both macro- and microscopically. Diabetic conditions did not affect the development of HCI-induced gastric lesions but significantly delayed the healing of these lesions. Daily administration of insulin returned high blood glucose levels to within normal ranges (120-140 mg/dl) and significantly antagonized the delayed healing of these lesions. The delayed healing in diabetic rats was also significantly promoted by recombinant human basic fibroblast growth factor (>300 ng/kg x 2) without any effect on blood glucose level. In normal rats, the mucosal levels of bFGF increased significantly in response to gastric injury at 3 days after HCI treatment. The mucosal bFGF levels in streptozotocin-diabetic rats were significantly lower under basal conditions before HCI treatment and did not increase after injury, yet such dysregulation of bFGF production was partially restored by insulin treatment. rhbFGF even at 1000 ng/kg had no effect on gastric acid secretion in either normal or streptozotocin-diabetic rats. These results suggest that diabetic conditions have deleterious influences on the healing of acute gastric lesions in both an insulin- and bFGF-sensitive manner, and that the administration of exogenous bFGF antagonizes the delayed healing of gastric lesions observed in diabetic animals.
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PMID:Impaired healing of gastric lesions in streptozotocin-induced diabetic rats: effect of basic fibroblast growth factor. 910 98

We examined the HCO(3)- stimulatory effects of L-NAME (N(G)-nitro-L-arginine methyl ester) in the proximal duodenum of streptozotocin (STZ)-induced diabetic rats and compared with those of 16,16-dimethyl prostaglandin E2 (dmPGE2) and vagal electrical stimulation. Male SD rats were given STZ (70 mg/kg) i.p., and the experiments were done using 1 approximately 6 week STZ-diabetic rats with blood glucose levels of >300 mg/dl. Under urethane anesthesia the HCO(3)- secretion was measured in the proximal duodenal loop using a pH-stat method and by adding 10 mM HCl. Hyperglycemic conditions appeared 1 week after STZ treatment and remained during 6 week-test period. The duodenal HCO(3)- secretory response to L-NAME was significantly decreased in STZ-diabetic rats; the degree of reduction was dependent on the duration of diabetes, and the stimulatory effect disappeared completely in rats after 5 approximately 6 weeks of diabetes. Intravenous administration of L-NAME markedly increased arterial blood pressure with significant decrease in heart rate in normal rats, whereas in STZ-diabetic rats this agent caused only pressor response without any effect on heart rate. STZ-diabetic rats also secreted significantly less amount of HCO(3)- from the duodenum in response to dmPGE2 and vagal electrical stimulation after 5 approximately 6 weeks of diabetes. These all changes observed in STZ-diabetic rats were significantly reversed by daily injection of insulin. These results suggest that 1) L-NAME failed to stimulate duodenal HCO(3)- secretion in STZ-diabetic rats, and 2) impairment of the duodenal HCO(3)- secretory ability in STZ-diabetic conditions is due to both vagal-dependent neuronal dysfunction and decreased sensitivity of the secreting cell.
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PMID:Failure of the nitric oxide synthase inhibitor to stimulate duodenal bicarbonate secretion in streptozotocin-diabetic rats. 912 71

Medicago sativa (lucerne) is used as a traditional plant treatment of diabetes. In the present study, administration of lucerne in the diet (62.5 g/kg) and drinking water (2.5 g/l) reduced the hyperglycaemia of streptozotocin-diabetic mice. An aqueous extract of lucerne (1 mg/ml) stimulated 2-deoxy-glucose transport (1.8-fold), glucose oxidation (1.7-fold) and incorporation of glucose into glycogen (1.6-fold) in mouse abdominal muscle. In acute 20 min tests, 0.25-1 mg/ml aqueous extract of lucerne evoked a stepwise 2.5-6.3-fold stimulation of insulin secretion from the BRIN-BD11 pancreatic B-cell line. This effect was abolished by 0.5 mM-diazoxide, and prior exposure to extract did not affect subsequent stimulation of insulin secretion by 10 mM-L-alanine, thereby negating a detrimental effect on cell viability. The effect of extract was potentiated by 16.7 mM-glucose and by 1 mM-3-isobutyl-1-methylxanthine. L-Alanine (10 mM) and a depolarizing concentration of KCl (25 mM) did not augment the insulin-releasing activity of lucerne. Activity of the extract was found to be heat stable and largely acetone insoluble, and was enhanced by exposure to acid and alkali (0.1 M-HCl and NaOH) but decreased 25% with dialysis to remove components with molecular mass < 2000 Da. Sequential extraction with solvents revealed insulin-releasing activity in both methanol and water fractions indicating a cumulative effect of more than one extract constituent. The results demonstrate the presence of antihyperglycaemic, insulin-releasing and insulin-like activity in the traditional antidiabetic plant, Medicago sativa.
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PMID:Pancreatic and extra-pancreatic effects of the traditional anti-diabetic plant, Medicago sativa (lucerne). 930 21

We previously reported the impaired HCO3- secretion and the increased mucosal susceptibility to acid in the duodenum of streptozotocin (STZ)-induced diabetic rats. In this study, we investigated the salutary effect of the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) on these changes and compared it with those of insulin. Animals were injected streptozotocin (STZ: 70 mg/kg, ip) and used after 1, 3-4, and 5-6 weeks of diabetes with blood glucose levels of > 300 mg/dL. Under urethane anesthesia the HCO3- secretion was measured in the proximal duodenal loop using a pH-stat method and by adding 10 mM HCl. L-NAME (20 mg/kg x 2) or insulin (4 units/rat) was administered sc for 4-5 weeks, starting 1 week after STZ treatment. The duodenal HCO3- secretory responses to various stimuli such as mucosal acidification (10 mM HCl for 10 min), 16,16-dimethyl prostaglandin E2 (dmPGE2: 10 micrograms/kg, i.v.), and vagal stimulation (0.5 mA, 2 ms, 3 Hz) were significantly decreased in STZ-treated rats, depending on the duration of diabetes. Repeated administration of L-NAME, starting from 1 week after STZ treatment, significantly reduced blood glucose levels toward normal values and restored the HCO3- responses to various stimuli in STZ rats, the effects being similar to those observed after supplementation of insulin. Diabetic rats developed duodenal lesions after perfusion of the duodenum with 150 mM HCl for 4 h, but this ulcerogenic response was significantly inhibited by the repeated treatment with L-NAME as well as insulin. We conclude that L-NAME is effective in ameliorating hyperglycemic conditions in STZ-diabetic rats, similar to insulin, and restores the impaired HCO3- secretion and the increased mucosal susceptibility to acid in diabetic rat duodenums.
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PMID:Impaired duodenal bicarbonate secretion in diabetic rats. Salutary effect of nitric oxide synthase inhibitor. 940 1

Advanced glycation end-product(s) (AGE) are formed in biological systems when reducing sugars react with amino groups on proteins. Long-lived proteins such as collagen and lens crystallins are known to be susceptible to AGE modification and may play a major role in the development of diabetes and other age-related pathologies. It has been previously suggested that AGE formation might affect the lifespan of experimental animals. Our study is the first to examine the effect of AGE accumulation on the life span of an organism, Drosophila melanogaster. We found that Drosophila melanogaster maintained at 24 degrees C accumulate significant AGE over their lifespan. Young flies (10 days old) had 44% less AGE than senescent flies (75 days old). We were able to reduce AGE accumulation in Drosophila melanogaster by raising the flies on a medium containing a known AGE inhibitor, aminoguanidine HCl. Reduction of AGE in flies failed to increase their mean lifespan, and high concentrations (40 mM) reduced the mean life span, which suggests that aminoguanidine is toxic at levels near those required for inhibition of AGE formation. However, the common fruit fly, Drosophila melanogaster, provides a simple model system to study the age-dependent accumulation of glycated proteins and their inhibition by novel compounds.
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PMID:Age-dependent accumulation of advanced glycation end-products in adult Drosophila melanogaster. 957 11

We used the sucrose preference test and taste nerve recording to investigate the effect of dietary biotin on the abnormal sucrose taste sensitivity and preferences seen during the course of diabetes mellitus. For this, we used Otsuka Long-Evans Tokushima fatty (OLETF) rats. The chorda tympani nerve (CT nerve) response to sucrose (> 1 M) was of greater relative magnitude in OLETF rats than in non-diabetic control (Long-Evans Tokushima Lean, LETO) rats, but the responses to other basic taste stimuli (such as HCl, quinine-HCl and L-glutamic acid) did not differ between the two groups. In behavioral experiments using a two-bottle preference test, solution intake for sucrose (> 50 mM) was higher in OLETF rats than in LETO rats. The neural responses to sucrose (1.5-2 M) in OLETF rats were lower when given a biotin-high diet (BH-OLETF) than when given a biotin-basal diet (BB-OLETF), but this was not true of the other basic tastes. However, there were no significant differences between BH-OLETF and BB-OLETF rats in terms of sucrose solution intake. These findings suggest that the enhanced sugar sensitivity observed in OLETF rats is probably the result of a genetic difference between OLETF and LETO rats, though the discrepancy can be modified by the dietary biotin level.
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PMID:Effects of dietary biotin on enhanced sucrose intake and enhanced gustatory nerve responses to sucrose seen in diabetic OLETF rat. 967 1


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