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

Both alloxan and streptozotocin produce beta-cell necrosis in the rat. Previous studies have shown protection against alloxan toxicity by D-glucose, D-mannose, and the nonmetabolized analogue 3-0-methyl-D-glucose and removal of this protective effect by D-mannoheptulose. The effect of several agents (i.v. infusion) against the beta-cell toxic effect of streptozotocin (60 mg./kg. i.v. in 24-hour-fasted 200-gm. male rats) was studied. Protection was determined by plasma glucose concentrations 24 and 48 hours later and, in certain experiments, by histologic examination of the islets. D-glucose and D-mannose provided no protection. Similarly, D-galactose, D-fructose, alpha-methyl-D-glucoside, D-L-glyceraldehyde, D-xylose, and D-glucosamine had no effect. However, 3-0-methyl-D-glucose administered immediately before streptozotocin resulted in progressive inhibition of beta-cell toxicity with complete protection at 0.83 mMoles per rat. The protective effect of 3-0-methyl-D-glucose was not altered by mannoheptulose. 2-Deoxy-D-glucose, which has no effect against alloxan, provided nearly complete protection against streptozotocin at 2.2 mMoles per rat. The effects of 3-0-methyl-D-glucose and 2-deoxy-D-glucose were additive and were not altered by glucose. Furthermore, the 3-0-methyl-D-glucose as well as 2-deoxy-D-glucose protective effects were still present, albeit attenuated, when these agents were given following the administration of streptozotocin. This is in contrast to alloxan, against which 3-0-methyl-D-glucose provides protection only when given before alloxan. 3-0-Methyl-D-glucose is the only carbohydrate protective against both streptozotocin and alloxan in the rat. However, several silent differences seem to exist between the mechanisms of beta-cytotoxic effects of these two diabetogenic compounds.
Diabetes 1976 Jul
PMID:Studies on streptozotocin diabetes. 13 82

It has been suggested that the hyperglucagonemia observed in diabetic animals and man may be due to an impairment of glucose uptake and metabolism by the alpha-cells resulting in a decreased production of ATP. To test this hypothesis glucose, ATP, glucagon, and insulin were measured in pancreatic islets of normal and alloxan or streptozotocin diabetic rats. Two experimental approaches were used. In the first, the pancreas was perfused in vitro for assessing insulin and glucagon release due to 10 mM amino acids with and without 5 mM glucose. These perfusions were performed in the presence and absence of insulin. After perfusion, the pancreas was frozen and processed for analysis of islet glucose, ATP, insulin, and glucagon content. The second approach was to investigate the islet sucrose, urea, and glucose spaces together with ATP, insulin, and glucagon content in vivo in normal and in insulin-treated and untreated streptozotocin diabetic rats. Perfusion of the pancreas in vitro with 5 mM glucose resulted in higher glucose content of normal islets than in alloxan and streptozotocin diabetic islets. Similarly in the in vivo studies, the intracellular glucose space of the streptozotocin diabetic islets was 30% the value found in normals. In the in vivo experiments, despite the relatively small intracellular glucose space of alpha-cell islets, the ATP content of these islets was only 15-20% lower than the ATP content of normal islets. In the in vitro experiments, perfusion with glucose resulted in ATP contents of alpha-cell islets and of normal mixed alpha-beta-cell islets which were indistinguishable. However, the ATP content of alpha-cell islets was maintained for prolonged periods in the absence of glucose in contrast to mixed islets, composed primarily of beta-cells, in which the ATP level decreased by 45% when glucose-free medium was perfused for sustained periods. Finally, insulin infused in high concentrations or administered to the diabetic animal had no effect on the glucose spaces or the ATP contents of normal or alpha-cell islets. It can be calculated that in vivo the intracellular glucose level of islets from streptozotocin treated rats is approximately 15 mM. Since in normals an extracellular glucose concentration of this magnitude inhibits stimulated glucagon release completely, it would seem unlikely that a lack of intracellular glucose is the cause of the apparent glucose "blindness" of the alpha-cells in diabetes. In fact, in perfusion studies as little as 2.5 mM free intracellular glucose was sufficient to suppress glucagon secretion from diabetic alpha-cells. The results of the ATP measurements clearly eliminate a possible energy deficit of diabetic alpha-cells as cause of the apparent glucose resistance of alpha-cells.
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PMID:Glucose and ATP levels in pancreatic islet tissue of normal and diabetic rats. 13 53

The effect of experimentally-induced diabetes mellitus on reproductive organ weights, serum and pituitary gonadotropin levels and serum testosterone levels was studied in 3-month old rats. In experiment 1, intact rats were treated with alloxan monohydrate or streptozotocin. In experiments 2 and 3, intact and castrated rats were rendered diabetic with alloxan (experiment 2) or streptozotocin (experiment 3). The duration of each experiment was 3 weeks. In each experiment diabetes resulted in body weight losses or reduced body weight gain, elevated serum glucose concentrations and reduced assessory sex gland weights (intact rats). Serum levels of testosterone were depressed (P less than 0.05 or P less than 0.01) in diabetic rats. Serum levels of LH were significantly (P less than 0.05) lower in intact diabetics than in controls when pooled data from the three experiments were compared. Serum levels of FSH were not affected by diabetes. Pituitary concentrations of FSH were elevated (P less than 0.05) in diabetics in two of the three experiments, while LH concentrations were elevated (P less than 0.05 or P less than 0.01) in diabetics in all experiments. The hypersecretion of gonadotropins in castrated rats was not affected by diabetes.
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PMID:Some effects of experimentally-induced diabetes on pituitary-testicular relationships in rats. 13

Hepatic plasma membranes prepared from rats rendered diabetic by streptozotocin bound approximately twice as much insulin per 50 mug protein as control membranes. Glucagon binding of diabetic and control membranes was virtually identical. This increased insulin binding was not due to a nonspecific effect of streptozotocin, decreased degradation of insulin slower dissociation from its receptor, or a selective higher yield of membranes prepared from the diabetic livers. Diabetic and control membranes both showed negative cooperativity. Scatchard analysis suggested that the difference in binding was due to an enhanced binding capacity of the diabetic membranes rather than increased affinity of the binding sites. Increased insulin binding of diabetic membranes was returned to normal by insulin treatment. These data are consistent with the postulate that there is an inverse relationship between circulating insulin levels and insulin binding and that insulin may modulate its own receptor. However, since it has been reported that fat, muscle, and hepatic tissue from rats made diabetic by alloxan administration are insensitive to insulin, the capacity for binding can not be the sole factor determining the response to insulin in diabetes mellitus. Therefore, sensitivity of the diabetic liver to insulin is determined, at least in part, by events subsequent to the binding of insulin to its receptor.
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PMID:Increased insulin binding by hepatic plasma membranes from diabetic rats: normalization by insulin therapy. 13 48

Duodenal calcium absorption and a vitamin D-dependent duodenal calcium-binding protein are depressed in rats with alloxan- or streptozotocin-induced diabetes. To test for possible abnormal vitamin D metabolism in diabetes we measured serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in control, streptozotocin diabetic, and insulin-treated diabetic rats. The serum concentration of 1,25-dihydroxyvitamin D was depressed in untreated diabetic rats to one-eighth of the level in controls and was restored to control levels by insulin treatment. The serum concentration of 25-hydroxyvitamin D was the same in all three groups. Hence, effects of diabetes on duodenal calcium transport can be explained by reduced concentrations of 1,25-dihydroxyvitamin D resulting either from failure of renal 1alpha-hydroxylation of 25-hydroxyvitamin D or increased catabolism of 1,25-dihydroxyvitamin D.
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PMID:Experimental diabetes reduces circulating 1,25-dihydroxyvitamin D in the rat. 14 Oct 98

Blood flow through various tissues of streptozotocin- and alloxan-diabetic and genetically obese rats was compared with that of controls by a radioisotopically labeled microsphere technique. Total cardiac output per unit body weight was unchanged in the diabetic group but decreased in the obese animals. The proportion of cardiac output received by the kidney and organs of the gastrointestinal tract was increased in the diabetic animals. Tissue hyperplasia appeared to be largely responsible. Blood flow per unit weight was markedly increased in the fat tissue of diabetic rats but was reduced in that of the obese rats, indicating a positive relationship between fat mobilization and blood flow. Blood flow in the hindlimbs, tail, skin, and spleen were all reduced in at least one diabetic group. Most of the changes observed appeared to progress with the duration of diabetes. Possible hormonal and metabolic causes are discussed. Some of the experimental changes observed may form useful models for diabetic vasculopathy.
Diabetes 1977 Aug
PMID:Effects of experimental diabetes and genetic obesity on regional blood flow in the rat. 14 36

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

The isolated perfused rat lung was used as a model to study the possible hormonal regulation of lipid metabolism in the mammalian adult lung. Experimental diabetes, whether induced by alloxan or streptozotocin, decreased the incorporation of [U-14C]glucose into neutral lipids and phospholipids of both the surfactant fraction and the residual fraction of the lung by 60-80%. Glucose incorporation into phosphatidylcholine and phosphatidylglycerol is decreased in experimental diabetes in both the surfactant and residual fractions to a comparable degree. Glucose incorporation is decreased in both the fatty acid and the glycerophosphocholine moieties of phosphatidylcholine isolated from the surfactant and residual fractions. Insulin treatment of normal animals 30 or 15 min prior to perfusion resulted in an approximate doubling of the incorporation of glucose into the phosphatidylcholine and phosphatidylglycerol isolated from the surfactant and residual fractions of the lung. The incorporation of glucose into palmitic acid isolated from phosphatidylcholine was also shown to increase similarly. The results of these investigations indicate that insulin may play a role in regulating the synthesis of the important lipid components of the mammalian pulmonary surfactant complex.
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PMID:Effect of experimental diabetes and insulin on lipid metabolism in the isolated perfused rat lung. 14 18

D-glucose in the pyranose (ring) form exists as two anomers. The alpha-anomer is more effective than the beta-anomer in promoting insulin secretion, suppressing that of glucagon, and protecting beta-cells against alloxan toxicity. Streptozotocin (SZ), a beta cell toxin, is composed of a cytotoxic moiety, 1-methyl 1-nitrosourea, attached to carbon-2 of glucose and exists as either of two anomers in the pyranose form. In 24-hour-fasted male rats, predominantly alpha- or predominantly beta-SZ was injected intravenously and plasma glucose levels were obtained 48 hours later. The alpha-anomer produced significantly greater beta-cell necrosis at doses of 30, 35, and 40 mg./kg. body weight. At higher doses, no differences between the alpha and beta anomers were observed. 3-O-Methyl glucose (3-OMG) protected against both SZ anomers; however, the alpha-SZ remained more toxic. Larger doses of glucose protected against the lower doses of SZ and, under such conditions, the individual glucose anomers appeared equally potent. Finally, mannitol at comparable molar concentrations was ineffective in protecting against the SZ toxicity. This study suggests that streptozotocin's beta cell toxicity is mediated through recognition by the beta cell. In addition, 3-OMG and, to a lesser but significant extent, glucose were shown to protect against the streptozotocin toxicity, whereas mannitol did not.
Diabetes 1977 Dec
PMID:Pancreatic beta cell toxicity by streptozotocin anomers. 14 86

Diabetes mellitus was induced in female Wistar rats by injections of either alloxan or streptozotocin, and their embryos were found to have significantly higher incidences (7.5%) of brain and heart abnormalities (non-closure of neural folds, and deformities of heart chambers) at mid-gestation than controls (2.2%). There were also increased numbers of resorptions (25% in diabetic animals: 7.2% in controls). Both drugs produced similar abnormalities. External and X-ray examination of 488 foetuses from streptozotocin-treated animals at 20 days showed eight cases of exomphalos, two cases of micrognathia with tongue protrusion, and 34 cases of incomplete sacral ossification. This last deformity occurred also in foetuses of mildly diabetic animals, and has been seen occasionally in infants of human diabetic mothers. Other evidence suggests that skeletal deformities may be due to hyperinsulinism in the foetuses of diabetic mothers. Even a mild or pre-diabetic condition may set the foetus at risk.
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PMID:Embryonic malformations in rats, resulting from maternal diabetes: preliminary observations. 14 55


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