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

The content of NAD+, NADH, NADP+, NADPH in the liver of normal, fasting rats, those on the low-carbohydrate diet and suffering from alloxan diabetes was studied as affected by nictotinamide. Changes in the NAD+ content, sum of nicotinamide coenzymes, the [NAD+] + [NADP+]/[NADH] +/- [NADPH] and [NAD+] + [NADH] (sum of nicotinamide coenzymes) ratios are mainly due to nicotinamide administration. Changes in the content of reduced forms of both nucleotides depend equally on nicotinamide administration and the physiological state of animals. Response of the rat organism to nicotinamide administration consists in a sharp intensification of NAD+ synthesis and in a less pronounced intensification of NADH, NADP+ and NADPH synthesis.
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PMID:[Content of nicotinamide coenzymes in rat liver under conditions of nicotinamide administration]. 2 48

Experimentally-induced alloxan diabetes was characterized in rats by a marked increase in the blood glucose level and by a number of disturbances in the concentration of metabolites and the activity of the enzymes of carbohydrate metabolism in the liver. Stimulation of gluconeogenesis in diabetes was judged by reduction of the redox condition of free NAD- and NADP-couples, by the increase in the concentration of phosphoenolpyruvate, malic oxaloacetate and phosphoenolpyruvate carboxykinase activity of the liver. Nicotinamide in a dose of 50 mg per 100 g of body weight caused a marked reduction in the blood glucose level of diabetic rats. An increase of the [NAD+]/[NADN], [NADP+]/[NADPN] ratio, a reduction of the concentration of phosphoenolpyruvate, malate and phosphoenolpyruvate carboxylase activity pointed to the inhibition of gluconeogenesis and stimulation of glycolysis in the liver of diabetic rats given nicotinamide.
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PMID:[Hypoglycemic effect of nicotinamide in rats with alloxan diabetes]. 2 43

To evaluate the role of the glucose residue of the diabetogenic substance streptozotocin, the effect of its aglucone derivate N-nitrosomethylurea was tested in Chinese hamsters. At a dose of 50 mg/kg body weight of N-nitrosomethylurea a triphasic blood glucose curve was recorded with an initial hyperglycaemic peak after 3 hours followed by a decrease at 6 hours. After 24 hours and during the following days the values were moderately elevated. There was a high mortality in the diabetic animals, about 80 per cent of them dying within one week. The approximate L.D. 50 of N-nitrosomethylurea injected intraperitoneally in non-fasting adult animals was about 125 mg/kg body weight at an observation time of 48 hours. On light microscopy, degenerative changes with nuclear pyknosis were seen after 3 hours in the pancreatic islet cells, followed by cellular disintegration. Both beta-, alpha2- and alpha1-cells were obviously affected. Pretreatment with 500 mg nicotinamide/kg body weight given intraperitoneally 10 minutes before the injection of N-nitrosomethylurea inhibited and hyperglycaemia and seemed to prevent the injurious effects of N-nitrosomethylurea on the islet cells. The results show that the glucose residue of the streptozotocin molecule is not necessary for the induction of diabetes in Chinese hamsters, but it seems to increase the selectivity of the toxic effects for the islet cells. This is a clear advantage in studies of experimental diabetes, especially when longer observation periods are desired.
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PMID:Diabetogenic effects of n-nitrosomethylurea in the chinese hamster. 12 26

Previous studies had shown that administration of streptozotocin to rats produces both diabetes and hemolysis and that both could be ameliorated by prior injections of diazoxide. Thus, it appeared pertinent to define the effect of streptozotocin on the red cell. In the present studies, streptozotocin administered in vivo to rats produced a rapid fall in red-cell-reduced glutathione. This effect was duplicated in vitro in incubated human red cells. Furthermore, it was demonstrated that glucose loading prior to bleeding modified the in-vitro red-cell GSH response to streptozotocin and that preincubation of red cells from fasted individuals with glucose, nicotinamide, and epinephrine (but not nicotinic acid) protected against the subsequent effect of streptozotocin on RBC GSH. The pattern of the RBC GSH response under each of these conditions is that which occurs in response to challenge with an oxidant, that is, with appropriate protection, oxidation stress produces an acute rise rather than falll in gsh. further, when glucose was present through both preincubation and test periods (i.e., in presence of streptozotocin) a third pattern of GSH response was observed--no change. The data are compatible with the postulate that the cytotoxic action of streptozotocin is dependent, in part, on an oxidant effect, and that glucose may protect through at least two mechanisms, that adrenergic stimulation can enhance protective mechanisms against redox insults and so contribute to maintenance of cell viability.
Diabetes 1976 Mar
PMID:Effect of streptozotocin on red-blood-cell-reduced glutathione: modification by glucose, nicotinamide, and epinephrine. 13 Feb 72

These investigations delineate the recently described suppression of a form of cellular hypersensitivity in mice with streptozotocin-induced diabetes mellitus using a variety of cell-mediated immunologic responses in animals with several different forms of diabetes. Streptozotocin- and alloxan-induced diabetic mice and db/db genetically determined diabetic mice showed reductions in the areas of inflammation around Schistosoma mansoni eggs injected into the pulmonary vasculature of 68, 70, 77%, respectively. In contrast, streptozotocin-induced diabetes had no effect on the nonimmunologic foreign body granuloma around divinyl benzene copolymer beads injected into the pulmonary arterioles. Animals protected from diabetes by treatment with nicotinamide before streptozotocin administration did not develop hyperglycemia and had normal areas of immunologic granuloma formation around schistosome eggs. Treatment with insulin reversed the suppression of schistosome egg granuloma formation in both streptozotocin- and alloxan-diabetic animals. Two additional in vivo parameters of cellular immunologic reactivity were examined in streptozotocin-induced diabetes: delayed footpad swelling was essentially eliminated; skin graft survival across the H-2 area was significantly prolonged from 10.2 days in the controls to 14.4 days in moderately diabetic A/J mice. These observations suggest that diabetes mellitus is associated with suppression of cell-mediated reactions in vivo and that the defect is reversible with insulin treatment.
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PMID:Induced and spontaneous diabetes mellitus and suppression of cell-mediated immunologic responses. Granuloma formation, delayed dermal reactivity and allograft rejection. 13 Mar 84

The uptake of the nicotinamide adenine dinucleotide (NAD)-precursors nicotinamide, nicotinic acid and tryptophan in the pancreatic islets of mice was studied by use of autoradiographic methods. The ability of these substances to prevent streptoxotocin diabetes was studied in the same species. It was found that only nicotinamide was strongly accumulated in the pancreatic islets and nicotinamide was also the only NAD-precursor which protected against the streptoxotocin diabetes. Apparently there is a relationship between the ability of the NAD-precursors to be taken up in the pancreatic islets and their ability to prevent streptoxotocin diabetes.
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PMID:The uptake in the pancreatic islets of nicotinamide, nicotinic acid and tryptophan and their ability to prevent streptozotocin diabetes in mice. 13 65

Multiple small injections of streptozotocin produce a delayed, progressive increase in plasma glucose in mice within 5-6 days after the injections, in association with pronounced insulitis and induction of type C viruses within beta cells. Multiple subdiabetogenic doses of streptozotocin in rats and multiple injections of another beta cell toxin, alloxan, in mice did not induce insulitis although hyperglycemia followed the injection of larger quantities of both agents. In mice, the prior injection of 3-O-methyl-D-glucose (3-OMG) or nicotinamide attenuated the diabetic syndrome produced by streptozotocin; however, 3-OMG was more protective. Rabbit antimouse lymphocyte serum, alone, provided partial protection but, when given together with either 3-OMG or nicotinamide, effectively prevented the streptozotocin-induced diabetic syndrome. Cessation of these preventive treatments was followed by the appearance of insulitis and diabetes. These findings suggest that multiple injections of streptozotocin induce, in susceptible hosts, the triad of direct beta cell cytotoxicity, virus induction within beta cells, and cell-mediated autoimmune reaction. These factors, acting separately or in concert, appear to induce a destructive insulitis and severe diabetes. The relative importance of each component and the factors governing host susceptibility remain to be clarified.
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PMID:Studies of streptozotocin-induced insulitis and diabetes. 14 53

A case of N-3 pyridylmethyl-N' 4 nitrophenyl urea (Vacor) rodenticide poisoning in a 52-year-old man is presented. Vacor is structurally related to alloxan and streptozotocin, agents that have been used extensively to produce diabetes mellitus in laboratory animals. Seven days after ingestion of Vacor, the patient presented in diabetic ketoacidosis complicated by postural hypotension and adynamic ileus. The patient recovered from ketoacidosis but has continued to require insulin. With infusion of arginine, glucagon rose from 185 to 650 pg./ml. and C-peptide from 0.5 to 3.4 ng./ml. Six weeks after onset of diabetes, no anti-islet-cell antibodies were detected. Muscle capillary basement membrane thickness on electron microscopy was found to be 1,918 +/- 194 A. The absence of hyperglycemia after Vacor ingestion should not lead to complacency on the part of the attending physician. The patient must be observed closely for development of ketoacidosis and treated prophylactically with nicotinamide, the suggested antidote.
Diabetes Care
PMID:Diabetes mellitus and autonomic dysfunction after vacor rodenticide ingestion. 15 23

Two patients ingested Vacor, a rodenticide containing the active ingredient N-3 pyridylmethyl-N'-p-nitrophenyl urea. Both patients developed ketosis-prone diabetes mellitus and severe autonomic neuropathy. Niacinamide therapy given nine hours after Vacor ingestion in one patient and 14 hours after ingestion in the other was not successful in preventing these sequelae. Physicians need to be aware of the toxicity of Vacor, and the potential therapeutic benefit of early niacinamide therapy.
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PMID:Diabetes mellitus and neuropathy following Vacor ingestion in man. 15 28

The renal oncogenic activity of streptozotocin in male Holtzman rats was significantly decreased by nicotinamide. Adenomas of the kidney were noted in 77% (21/28) of the animals treated with single iv dose of the streptozotocin, 50 mg/kg, while only 18% (5/28) of animals given nicotinamide ip, 350 mg/kg, 10 min before and 180 min after the same dose of streptozotocin had demonstrable renal tumors. Moreover, the renal adenomas induced by streptozotocin alone occurred sooner and were generally larger when compared with those in the animals treated with the nicotinamide-streptozotocin combination. The 50 mg/kg dose of streptozotocin was diabetogenic in all rats, but the diabetic state was not permanent. Spontaneous recovery from the diabetes was first noted after 8 and 10 months of followup, and after 16 months none of the surviving rats were diabetic.
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PMID:Modification of renal tumorigenic effect of streptozotocin by nicotinamide: spontaneous reversibility of streptozotocin diabetes. 17 79


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