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

The purpose of this investigation was to ascertain the ability of phenazine methosulfate (PMS) to improve the streptozotocin (STZ) and alloxan induced diabetic condition in vivo as determined by changes in blood and urine glucose levels and by alteration in the secretion of insulin by isolated islets. STZ and alloxan diabetes was induced in male albino rats (200-250 g body weight). A single injection of PMS (6.0 mg/kg) or nicotinamide (500 mg/kg) simultaneously with diabetic doses of either STZ or alloxan caused a significant reduction in blood and urine glucose levels three days after the injection. The reduction in glycemic levels was greater with PMS than with nicotinamide. Daily PMS (0.5 mg/kg) injection, initiated 5, 10, 20 or 30 days after the development of STZ- and alloxan-diabetes, caused a significant decrease in blood and urine glucose levels and also increased body weight determined 60 days after STZ or alloxan administration. These effects were observed even if the injections were initiated 20 or 30 days after the onset of the diabetic syndrome. Glucose stimulated insulin secretion was significantly inhibited by pre-incubation of isolated islets for one hour at 37 degrees C with either STZ or alloxan. However, insulin secretion was induced by PMS in the STZ or alloxan pretreated islets. Nicotinamide neither protected nor induced insulin secretion under similar conditions. The level of insulin secretion induced by PMS whether in the normal islets or in islets previously exposed to the B-cytotoxic agents were comparable in quantity to glucose (17 mM)-stimulated insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction in blood and urine glucose levels in streptozotocin and alloxan diabetes by phenazine methosulfate. 253 44

Nicotinamide which is an inhibitor of poly (ADPR) synthetase and precursor of NAD has been observed to prevent diabetes in some experimental models possibly by protecting beta cells. To determine whether nicotinamide could cure or prevent type 1 diabetes, we administered large doses (0.5 g/Kg/d) to BB rats. When used in the 45 days following diagnosis nicotinamide failed to bring remission. As a preventive treatment, nicotinamide administered between the 40th and 90th day of age, alone or in association with desferrioxamine did not significantly lower the incidence of diabetes (23% and 30.8% respectively vs. 56.6%). When used earlier, immediately after weaning, nicotinamide did not affect the incidence of diabetes in this model (62.5%). The degree of protection was not comparable with that obtained with cyclosporin A (15% of diabetic animals). Histology study of the pancreas from the animals killed either immediately or 1 year after treatment revealed no endocrine tumor. These findings suggest that in BB rats nicotinamide has little or no effect on the course of autoimmune diabetes mellitus thus dampening the high hopes for this drug in the treatment of human diabetes.
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PMID:High dose nicotinamide fails to prevent diabetes in BB rats. 253 59

Under the sponsorship of the National Institute on Aging and the National Institute of Diabetes and Digestive and Kidney Diseases, the Life Sciences Research Office of the Federation of American Societies for Experimental Biology held a workshop entitled, "The Role of Folate and Vitamin B-12 in Neurotransmitter Metabolism and Degenerative Neurological Changes Associated with Aging." The purpose of the May 1988 workshop was to bring together scientists from various disciplines to identify opportunities for research on an important topic relating to neuroscience, nutrition and aging.
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PMID:The role of folate and vitamin B-12 in neurotransmitter metabolism and degenerative neurological changes associated with aging: proceedings of a workshop. 256 13

The activity of tyrosine hydroxylase (TOH), the rate-limiting enzyme in norepinephrine biosynthesis, was measured in selected sympathetic ganglia to develop a quantitative measure of sympathetic autonomic neuropathy in streptozocin-induced diabetic rats. Surprisingly, TOH activity was elevated twofold in diabetic prevertebral ganglia innervating the alimentary tract (i.e., superior mesenteric, celiac, and inferior mesenteric), which has terminal processes that develop neuroaxonal dystrophy in this model system. TOH activity of paravertebral ganglia (i.e., superior cervical and stellate) with nonalimentary targets was not increased in the same animals. Increased TOH activity in the prevertebral ganglia 1) developed within the 1st wk of diabetes and persisted for 10 mo, 2) did not represent a change in TOH affinity for d-1,6-methyl-5,6,7,8- tetrahydropterine cofactor, 3) was prevented by both nicotinamide pretreatment and early institution of insulin therapy, and 4) did not develop as a result of classical transsynaptic induction. Pair-feeding experiments confirmed that the most likely cause of increased TOH activity in this system was the marked hypertrophy and hyperplasia of the diabetic bowel resulting from compensatory hyperphagia. We conclude that TOH activity does not represent a suitable marker for sympathetic autonomic neuropathy in this experimental system. Rather, the increase appears to be an example of a selective increase in the synthesis of neurotransmitter enzymes, possibly in response to increased trophic support provided by the expanded target, i.e., the hypertrophic gut. The additional synthetic stress imposed on prevertebral neurons by the expansion of the innervation of the alimentary target coupled with the complex diabetic metabolic milieu may contribute to the development and selective distribution of dystrophic axonopathy to the innervation of the alimentary tract.
Diabetes 1989 Aug
PMID:Tyrosine hydroxylase activity in sympathetic nervous system of rats with streptozocin-induced diabetes. 256 57

To establish methods for stimulation of the growth and differentiation of fetal endocrine pancreatic cells, a technique for the in vitro production of fetal porcine isletlike cell clusters (ICCs) was used. By varying the composition of the culture medium with different glucose concentrations and the addition to the culture medium of insulin, growth hormone (GH), amino acids, or nicotinamide, we estimated the formation of ICCs and their hormone content. High glucose content (28.0 mM) stimulated the formation of abundant ICCs that contained decreased amounts of insulin. In contrast, culture at a low (5.6-mM) glucose concentration increased the ICC insulin content but decreased the number of ICCs formed. Addition of seven times the normal amount of amino acids hampered both the formation of ICCs and their insulin content. Neither insulin nor GH supplementation of the medium influenced the ICC insulin content, but GH stimulated an abundant outgrowth of ICCs containing relatively high insulin concentrations. However, ICCs formed under these circumstances contained less than 10% of the insulin content of adult islets, and further work has to be carried out to identify factors responsible for further differentiation of the fetal porcine pancreas.
Diabetes 1989 Jan
PMID:Effects of culture conditions on formation and hormone content of fetal porcine isletlike cell clusters. 264 47

The addition of 3-aminobenzamide (a potent inhibitor of poly(ADP-ribose)synthetase) into the incubation medium, prevents streptozotocin-induced inhibition of glucose-stimulated insulin release from isolated islets [control 142 +/- 14 microU X islet-1 X h-1; streptozotocin (0.5 mg/ml) 31 +/- 8; 3-aminobenzamide (1.0 mg/ml) 96 +/- 11; streptozotocin plus 3-aminobenzamide 122 +/- 19]. In vivo, intraperitoneal 3-aminobenzamide 300 mg/kg body weight prevents the appearance of overt diabetes in streptozotocin-treated rats. These protective effects of 3-aminobenzamide are dose-dependent and are similar to those exerted by nicotinamide. Taking into account that poly ADP-ribosylation is involved in the repair of damaged DNA, the protection exerted by 3-aminobenzamide against the diabetogenic effect of streptozotocin strongly supports the view that this acute effect may be a major consequence of the activation of DNA repair mechanisms in islet cells.
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PMID:Protective effect of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase, against streptozotocin-induced diabetes. 293 87

Nicotinamide was given for 6 months to rats with streptozotocin induced diabetes. Presence of glomerular depositions (mesangial distribution) of IgG was evaluated with immunofluorescence technique. The immunofluorescence staining of the nicotinamide-treated diabetic rats was significantly less pronounced than that of the untreated diabetic rats. Normal age matched controls showed no such staining. The results indicate that nicotinamide retarded the development of the diabetic nephropathy. The findings might be explained by a normalizing effect of nicotinamide on a disturbed tryptophan and/or nicotinamide adenine dinucleotide metabolism. A metabolic hypothesis is formulated, which is consistent with the "glucose overutilization" theory.
Diabetes Res 1985 Nov
PMID:Protective effect of nicotinamide against nephropathy in diabetic rats. 293 4

Previously we have shown that nicotinamide prevents spontaneously occurring diabetes associated with insulitis in non-obese diabetic (NOD) mice. In this study we injected nicotinamide (0.5 mg/g) or saline (0.01 ml/g) into female NOD mice daily during a period between 4 and 16 weeks of age. At the end of the treatment, periductal and perivascular lymphocytic infiltration in submandibular glands was observed in 91% of saline-injected control mice and 36% of nicotinamide-injected mice (P less than 0.01). No significant difference was observed in the prevalence of anti-salivary duct antibodies or antinuclear antibodies between the nicotinamide group and the saline group. Nicotinamide may alter cell-mediated, but not humoral, immunity to salivary gland cells, resulting in the prevention of submandibulitis.
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PMID:Nicotinamide prevents lymphocytic infiltration in submandibular glands but not the appearance of anti-salivary duct antibodies in non-obese diabetic (NOD) mice. 293 77

Antibody-dependent cell-mediated cytotoxicity (ADCC) by splenic mononuclear cells was measured in female non-obese diabetic (NOD) mice and age-matched ICR mice. No significant difference in ADCC activities was observed between the two groups when all the NOD mice were pre-diabetic. ADCC activities in diabetic NOD mice were significantly higher than those in age-matched ICR mice (P less than 0.001). Nicotinamide, known to prevent the diabetes of the NOD mouse, strongly inhibited ADCC by the mononuclear cells from diabetic NOD mice. Kinetic studies revealed that the inhibition was non-competitive.
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PMID:Elevated antibody-dependent cell-mediated cytotoxicity and its inhibition by nicotinamide in the diabetic NOD mouse. 294 61

Insulin-dependent diabetes develops when more than 90% of the insulin containing B cells are destroyed. The present study investigates whether the target B cells can counteract the damaging effects of cytotoxic substances. Purified islet cells were first exposed for 3-10 min to t-butylhydroperoxide, alloxan, streptozotocin, or B-cell surface antibodies plus complement, then cultured for 20 hr before the percent of dead cells was counted. t-Butylhydroperoxide destroyed all islet cell types whereas the three other agents exerted a dose-dependent toxicity upon islet B cells only. The survival of drug- and complement-treated cells varied with the culture conditions present between the initial cellular attack and the moment of cell death. For the four B-cell toxic agents tested, an increase in medium glucose following any of these treatments reduced the percent of dead cells. This protective effect was not observed with galactose or fructose, nor could it be induced in islet non-B cells; it was additive to the protective action glucose induced during preincubation of the cells prior to their exposure to certain cytotoxic agents such as alloxan. Nicotinamide also enhanced the survival of drug-treated B cells, irrespective of the damaging compound. The vitamin was most effective when applied immediately after the initial drug or complement treatment; it also protected islet non-B cells--in contrast to glucose. The present in vitro study has led to the recognition of defense mechanisms in pancreatic B cells. Physiologic compounds such as glucose and nicotinamide were found to stimulate islet B cells to counteract the damaging effects of B-cell toxic conditions. It is conceivable that the events involved in this protection are implicated in the pathogenesis and/or prevention of insulin-dependent diabetes.
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PMID:Pancreatic B cells possess defense mechanisms against cell-specific toxicity. 294 62


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