Diabetes enhances dental caries and apical periodontitis in caries-susceptible WBN/KobSlc rats

Many epidemiologic studies have suggested that diabetes may be an important risk factor for periodontal disease. To determine whether diabetes induces or enhances periodontal disease or dental caries, dental tissue from diabetic male and nondiabetic female WBN/KobSlc rats and male and female age-matched nondiabetic F344 rats was analyzed morphologically and morphometrically for these 2 types of lesions. Soft X-ray examination revealed that the incidence and severity of both molar caries and alveolar bone resorption were much higher in male WBN/KobSlc rats with chronic diabetes than in nondiabetic female rats of the same strain. Histopathologic examination showed that dental caries progressed from acute to subacute inflammation due to bacterial infections and necrosis in the pulp when the caries penetrated the dentin. In the most advanced stage of dental caries, inflammatory changes caused root abscess and subsequent apical periodontitis, with the formation of granulation tissue around the dental root. Inflammatory changes resulted in resorption of alveolar bone and correlated well with the severity of molar caries. Our results suggest that diabetic conditions enhance dental caries in WBN/KobSlc rats and that periodontal lesions may result from the apical periodontitis that is secondary to dental caries.     

Effect of vanadate administration on polyol pathway in diabetic rat kidney.

Effect of oral administration of sodium orthovanadate for three weeks on polyol pathway in renal cortex and medulla was studied in control and alloxan diabetic rats. An enhancement in aldose reductase in cortex and medulla and sorbitol dehydrogenase in cortex was observed in alloxan diabetic rats. Despite depressed insulin secretion, vanadate treatment to diabetic rats counteracted hyperglycemia, normalized elevated enzyme activities and glucose level, prevented medullary sorbitol accumulation and markedly checked increase in kidney weight. These results show that vanadate causes marked improvement in renal hypertrophy and has an antidiabetogenic effect on polyol pathway in diabetic kidney.     

Studies on gluconeogenesis and ketogenesis in isolated hepatocytes from alloxan diabetic rats.

Gluconeogenesis and ketogenesis were studied in isolated hepatocytes obtained from normal and alloxan diabetic rats. Insulin treatment maintained near-normal blood glucose levels and caused an increase in glycogen deposition. The third day after insulin withdrawal the rats displayed a diabetic syndrome marked by progressive hyperglycemia and glycogen depletion. Net glucose production in liver cells isolated from alloxan diabetic rats progressively increased with time up to 72 hr after the last in vivo insulin injection. Maximal glucose production was observed at 72 hr with 10 mM alanine, lactate, pyruvate, or fructose. Glucose production decreased at 96 hr. The same pattern was observed with the incorporation of labeled bicarbonate into glucose. Ketogenesis in liver cells and hepatic lipid content also peaked at 72 hr.     

Therapeutic effects of stem cell on hyperglycemia,hyperlipidemia, and oxidative stress in alloxan-treated rats

Diabetes mellitus is the most common endocrine disorder that affects more than 285 million people worldwide. The purpose of this study was to investigate the effect of mesenchymal stem cells (MSCs) from the bone marrow of albino rats, on hyperglycemia, hyperlipidemia, and oxidative stress induced by intraperitoneal injection (i.p.) of alloxan at a dose of 150 mg/kg in rats. Injection of alloxan into rats resulted in a significant increase in serum glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, and sialic acid level and a significant decrease in serum insulin, high density lipoprotein-cholesterol, vitamin E, and liver glycogen as compared to their corresponding controls. Also, oxidative stress was noticed in pancreatic tissue as evidenced by a significant decrease in glutathione level, superoxide dismutase, glutathione-S-transferase activities, also a significant increase in malondialdehyde and nitric oxide levels when compared to control group. Treatment of diabetic rats with MSCs stem cells significantly prevented these alterations and attenuated alloxan-induced oxidative stress. In conclusion, rat bone marrow harbors cells that have the capacity to differentiate into functional insulin-producing cells capable of controlling hyperglycemia, hyperlipidemia, and oxidative stress in diabetic rats. This may be helpful in the prevention of diabetic complications associated with oxidative stress.     

Moderate physical training increases brain insulin concentrations in experimental diabetic rats

Insulin is an important modulator of growth and metabolic function in the central nervous system. The aim of this study was to investigate the influence of swimming physical training (at 32 degrees +/- 1 degree C, 1 hr/day, 5 days/week, with an overload equivalent to 5% of the body weight, for 4 weeks) on brain insulin concentrations in alloxan induced type 1 diabetic rats. Training attenuated hyperglycemia but had no effect on insulinemia in diabetic rats. Hematocrit and blood albumin values remained without changes. Brain insulin did not change in diabetic rats. However, physical training increased the concentration in both control and diabetic rats. It is concluded that in the present experimental conditions, diabetes had no influence on brain insulin, however moderate physical training increased the hormone in both control and diabetic animals.     

Effect of insulin therapy on renal changes in spontaneously diabetic Torii rats.

The spontaneously diabetic Torii (SDT) rat has recently been established as an animal model of non-obese type 2 diabetes, in which ocular complications severe occur. However, the function and morphological features of the diabetic renal lesions in SDT rats have not been reported in detail. Therefore, we evaluated changes over time in renal lesions in SDT rats. In addition, SDT rats were treated with insulin to observe whether these renal complications are caused by hyperglycemia. Renal functional parameters and renal lesions were monitored in SDT rats from 8 to 68 weeks of age. Sprague-Dawley (SD) rats of similar age were used as control animals. In the insulin-treated group of SDT rats, insulin pellets were implanted at 24 weeks of age to compare the development of renal lesions. The SDT rats began to develop hyperglycemia at 20 weeks of age. In the histopathological examination of the kidney, glycogen deposition of the renal tubular epithelium and renal tubular dilation were observed from 24 weeks of age in the untreated SDT rats, and the changes in the renal tubules markedly progressed with aging. Moreover, thickening of the glomerular basement membrane was observed from 32 weeks of age. At 50 weeks of age, the glomeruli showed increase of mesangial matrix, with predominantly diffuse lesions showing by 68 weeks of age. The mesangial proliferation gradually progressed. In the SD rats, no renal lesions were present at 50 and 68 weeks of age. SDT rats with insulin treatment remained normoglycemic throughout observation and their renal functional parameters were normal. Glycemic control in SDT rats prevented the development of renal lesions. The features of SDT rats indicate their usefulness as an animal model for investigating diabetic nephropathy.     

Control of hyperglycemia and retardation of cataract by mulberry (Morus indica L.) leaves in streptozotocin diabetic rats

Dried leaf powder of mulberry (M. indica L.) when given along with the diet at 25% level to streptozotocin induced diabetic male Wistar albino rats for 8 weeks, controlled hyperglycemia, glycosuria, albuminuria and retarded onset of retinopathy. Untreated diabetic rats showed hyperglycemia, glycosuria, albuminuria and developed lenticular opacity after 8 weeks of experimental period.     

Detection of Caries-Inducing Microorganisms in Hyposalivated Rats without Infection of Mutans Streptococci

Rampant dental caries was induced in hyposalivated rats fed a high sucrose diet without infection of mutans streptococci, in which increased numbers of lactobacilli and S. aureus were demonstrated in the oral flora. Administration of either penicillin or piperacillin, effective against all isolates of lactobacilli, markedly inhibited the caries induction in these rats, while severe dental caries was induced in hyposalivated rats given vancomycin that is inhibitory against S. aureus. These results suggested that certain lactobacilli might induce dental caries in hyposalivated rats fed a sucrose diet. Three strains of Lactobacillus species isolated from the hyposalivated rats were made resistant to erythromycin. The caries-inducing activity of these erythromycin-resistant lactobacilli was studied in hyposalivated rats giving erythromycin in the drinking water at a concentration of 500 μg/ml. After a 61-day experimental period, severe dental caries was induced in hyposalivated rats infected with L. fermentum TY1R. On the other hand, low caries incidence was found in hyposalivated rats infected with either L. acidophilus TY7R or L. plantarum TY3R. These results indicate that L. fermentum may be one of causative agents of dental caries in hyposalivated rats fed a sucrose diet.     

Antioxidant effect of Boerhavia diffusa L. in tissues of alloxan induced diabetic rats

Administration of B. diffusa leaf extract (BLEt; 200 mg/kg) for 4 weeks resulted in a significant reduction in thiobarbutric acid reactive substances and hydroperoxides, with a significant increase in reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione--S-transferase in liver and kidney of alloxan induced diabetic rats. The results suggest that BLEt has remarkable antidiabetic activity and can improve antioxidant status in alloxan induced diabetic rats.     

Mechanism of induction of cytochrome P-450ac (P-450j) in chemically induced and spontaneously diabetic rats

Previous studies demonstrated that a microsomal high-affinity N-nitrosodimethylamine demethylase activity and cytochrome P-450ac (an acetone/ethanol-inducible form) were induced by streptozotocin-induced diabetes in rats. In the present work, the induction was studied in detail in two chemically induced (by streptozotocin and alloxan) diabetic rat models and one spontaneously (BB/Wor) diabetic rat model. All the diabetic conditions caused increases in three parameters: (a) microsomal N-nitrosodimethylamine demethylase activity which is known to be a good indicator of the level of P-450ac; (b) the levels of P-450ac as determined by immunoblot analysis; and (c) the levels of mRNA of P-450ac as determined by hybridization assays with a cDNA probe for this enzyme. These increases were abolished by treatment of the diabetic rats with insulin. The results suggest that the pathophysiological condition of diabetes is responsible for the induction of P-450ac and elevation of mRNA is involved in all of the three diabetic models investigated.     

Diabetes and host resistance. I. Effect of alloxan diabetes upon the phagocytic and bactericidal efficiency of rat leukocytes for Pneumococcus

Briscoe, H. Frances (University Medical Center, Jackson, Miss.), and Fred Allison, Jr. Diabetes and host resistance. I. Effect of alloxan diabetes upon the phagocytic and bactericidal efficiency of rat leukocytes for pneumococcus. J. Bacteriol. 90:1537-1541. 1965.-Chronic diabetes mellitus was induced in rats with alloxan monohydrate. Glycosuria persisted for the 6 weeks of study, but ketonuria was never encountered. The cellular composition of peritoneal exudate recovered from diabetic rats after starch aleuronat administration was the same as that obtained from normal rats. The quantity of exudate recovered from the diabetic rats was thought to be less than that obtained from normal rats subjected to the same irritant. Phagocytosis was found to be essentially the same for both diabetic and normal cells when suspended in normal saline. The killing efficiency of harvested peritoneal phagocytes suspended in saline from both diabetic and normal rats for type 1 pneumococcus was compared and no difference between the groups was found.     

Alpha-glucosidase inhibition from a Chinese medical herb (Ramulus mori) in normal and diabetic rats and mice

Alpha-glucosidase inhibitors are oral antidiabetic drugs. A traditional Chinese medical herb, Sangzhi (Ramulus mori), appears to have properties similar to those of alpha-glucosidase inhibitors. The effects of an aqueous extract of Shangzhi (SZ) were studied in normal and alloxan diabetic rats and mice, and these results compared with those for acarbose, an alpha-glucosidase inhibitor. In our grade-dose studies, SZ was found to lower and prolong the zenith of blood glucose concentration (ZBG) after sucrose or starch loading and stabilize blood glucose levels in fasting normal and alloxan diabetic mice. After 2 weeks of SZ administration with high-calorie chow or a normal diet, the fasting and non-fasting blood glucose concentrations in alloxan diabetic mice and rats were decreased. In alloxan rats, the blood fructosamine concentration was lowered. Results for acarbose and SZ were similar. These indicate that SZ has alpha-glucosidase inhibitory effects.     

Glomerular hemodynamic and structural alterations in experimental diabetes mellitus

Elevated glomerular filtration rate (GFR) is a frequent finding in patients with early insulin-dependent diabetes mellitus (IDDM). The mechanisms responsible for this glomerular hyperfiltration in IDDM are unclear. Rats made diabetic with alloxan or streptozotocin, and treated daily with supplemental insulin, have moderate hyperglycemia and elevated GFR, and thus have been used to study mechanisms of glomerular hyperfiltration in diabetes. Renal micropuncture techniques have shown that single-nephron GFR (SNGFR) is elevated in moderately hyperglycemic diabetic rats. In some cases, this is because of elevated glomerular capillary pressure (Pgc), but in other cases, Pgc is normal despite elevated SNGFR. Several potential mediators of increased SNGFR have been examined, including hyperglycemia, increased glomerular prostaglandin production, and decreased sensitivity of the tubuloglomerular feedback mechanism. Renal failure is a common complication of human IDDM. Diabetic rats with long-term moderate hyperglycemia have been used to study the mechanism by which glomerular injury develops in diabetes mellitus. It has been postulated that glomerular hyperfiltration or some determinant of elevated GFR in early diabetes may ultimately cause glomerular damage, leading to a progressive loss of renal function (diabetic nephropathy). Diabetic rats with long-term moderate hyperglycemia, however, do not develop characteristic glomerular lesions of human diabetic nephropathy and, in fact, develop only minimal glomerular injury even after 1 year of diabetes. Thus, although the diabetic rat with moderate hyperglycemia may be useful to study the mechanisms of glomerular hyperfiltration in early diabetes, it may not be an appropriate model of renal failure in IDDM.     

The use of xanthine oxidase for a specific and sensitive fluorimetric determination of 6-mercaptopurine in serum

Excretion of urinary N-acetyl-beta-D-glucosaminidase has been found to be elevated in diabetic humans and rats. This urinary glycosidase may reflect blood sugar control over time, since it has been significantly and positively correlated with hemoglobin A1 in children with insulin-dependent diabetes. Other studies have suggested that urinary NAG may predict diabetic nephropathy. In order to more carefully define the relationship between urinary NAG excretion and blood and urine sugars, hemoglobin A1, and microalbuminuria, 48 rats were made diabetic by the use of streptozotocin. All rats were uninephrectomized at 3 weeks. Of these, 23 were treated with daily insulin injections, 25 were untreated, and both groups were compared to 13 control, nondiabetic rats. Urine volume, glucose, albumin, and blood sugar were all significantly (P less than 0.05) elevated in the untreated rats compared to the treated and control groups. Urinary NAG:UCr was significantly (P less than 0.01) elevated in the untreated group with lower but still elevated levels (P less than 0.05) in the treated rats. To further define the time course of the increase in UNAG:UCr 12 rats were followed serially at 12-hr intervals for 92 hr after streptozotocin. Urinary NAG increased significantly (P less than 0.05) at 12 hr after streptozotocin injection and reached a plateau at 36 hr while hemoglobin A1 did not rise until 2 weeks after onset of hyperglycemia. Urinary NAG increases more rapidly than hemoglobin A1 after onset of hyperglycemia and glycosuria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes with time in the oral microflora and dental caries induction in hyposalivated rats fed on sucrose diet.

The effects of hyposalivation on the induction of dental caries and the change in oral microflora were examined at weekly intervals in Sprague-Dawley rats fed on diet 2000 containing 56% sucrose. In hyposalivated rats, significant dental caries was induced within one week and its severity increased with the experimental period. Bacteriological examinations demonstrated that the number of total cultivable microorganisms, lactobacilli and Staphylococcus aureus increased significantly shortly after surgical induction of hyposalivation, while the number of streptococci and yeasts did not increase significantly until the 7th week, beyond which time remarkable gross caries developed. A positive correlation was found between the caries score and the recovery of lactobacilli from mandibles of hyposalivated rats, while there was no statistically significant correlation between the caries score and the recoveries of S. aureus. On the other hand, dental caries was not induced in control rats fed on sucrose diet with no surgically-induced hyposalivation. It was also found that the number of lactobacilli increased significantly shortly after diet 2000 was given to control rats, but S. aureus was rarely recovered from the mandibles of control rats throughout the experiments. The roles of lactobacilli and S. aureus in the induction of dental caries under the hyposalivated condition were discussed and it was suggested that lactobacilli may play some significant role in the induction of dental caries in hyposalivated rats.     

The effects of diet on the incidence of periodontitis in rats

Four groups of 60 male Alpk:APfSD rats were fed different nutritionally comparable diets for 107 weeks with interim sacrifices at 26, 53 and 77 weeks in order to compare the effect of diet on the incidence of oral disease. Changes in the oral and nasal cavities were assessed by histopathology. Oro-nasal fistulation and severe periodontitis were associated with diets containing fibres originating from oats and barley. An expanded ground diet induced the most severe lesions. Aspects of the pathogenesis of the lesions observed are discussed.     

Biochemical studies on hypoglycemic effect of Aavirai kudineer: a herbal formulation in alloxan diabetic rats

Aavirai Kudineer (AK) is an herbal decoction of seven botanical drugs, cited in the Gunapadam; a Tamil Siddha medical text. The anti-diabetic efficacy of this formulation was evaluated using alloxan-induced diabetic and normal rats. Glucose tolerance was observed within 1 hr in AK-treated rats (10 ml/kg body ) as compared to control. A significant decrease in the severe hyperglycemia characteristic of alloxan diabetes was noted after 15 days of AK treatment. Further AK treatment reversed the elevated urea, creatinine, cholesterol and decreased protein values to near normal levels. Assay of glycogen content and chief carbohydrate-metabolizing enzymes, viz. hexokinase, glucose-6-phosphatase and fructose 1,6 diphosphatase in the liver of diabetic and AK-treated diabetic rats clearly ascertains the hypoglycemic efficacy of this formulation. The mode of action of this herbal formulation remains to be elucidated.     

Protective role of D-saccharic acid-1,4-lactone in alloxan induced oxidative stress in the spleen tissue of diabetic rats is mediated by suppressing mitochondria dependent apoptotic pathway

The present study investigated the role of D-saccharic acid 1,4-lactone (DSL) in the spleen tissue of alloxan (ALX) induced diabetic rats. Diabetes was induced in rats by injecting ALX (at a dose of 120 mg/kg body weight) intraperitoneally in sterile normal saline. Elevated levels of blood glucose, glycosylated Hb and TNFα decreased levels of plasma insulin and disturbed intra-cellular antioxidant machineries were detected in ALX exposed animals. Oral administration of DSL at a dose of 80 mg/kg body weight, however, restored these alterations in diabetic rats. Studies on the mechanism of ALX-induced diabetes showed that hyperglycemia caused disruption of mitochondrial membrane potential in the spleen, released cytochrome C in the cytosol, activated caspase 3 and ultimately led to apoptotic cell death. Results suggest that DSL possesses the ability of protecting the spleen tissue from ALX-induced hyperglycemia and thus could act as an anti-diabetic agent in lessening diabetes associated spleen dysfunction.     

Protective role of D-saccharic acid-1,4-lactone in alloxan induced oxidative stress in the spleen tissue of diabetic rats is mediated by suppressing mitochondria dependent apoptotic pathway

The present study investigated the role of D-saccharic acid 1,4-lactone (DSL) in the spleen tissue of alloxan (ALX) induced diabetic rats. Diabetes was induced in rats by injecting ALX (at a dose of 120 mg/kg body weight) intraperitoneally in sterile normal saline. Elevated levels of blood glucose, glycosylated Hb and TNFα decreased levels of plasma insulin and disturbed intra-cellular antioxidant machineries were detected in ALX exposed animals. Oral administration of DSL at a dose of 80 mg/kg body weight, however, restored these alterations in diabetic rats. Studies on the mechanism of ALX-induced diabetes showed that hyperglycemia caused disruption of mitochondrial membrane potential in the spleen, released cytochrome C in the cytosol, activated caspase 3 and ultimately led to apoptotic cell death. Results suggest that DSL possesses the ability of protecting the spleen tissue from ALX-induced hyperglycemia and thus could act as an anti-diabetic agent in lessening diabetes associated spleen dysfunction.     

Cardiac dysfunction in isolated perfused hearts from spontaneously diabetic BB rats

The purpose of this investigation was to examine cardiac function and biochemistry in spontaneously diabetic BB rats, a strain in which diabetes occurs spontaneously and closely resembles insulin-dependent diabetes in humans. The study involved two groups: nondiabetic littermates of BB rats and BB diabetic rats treated daily with a very low insulin dose such that the rats were severely hyperglycemic and hyperlipidemic. The hearts from these two groups were isolated and heart function (using isolated perfused working hearts) and biochemistry were examined 6 weeks after the onset of diabetes. BB diabetic rats exhibited a lower calcium-stimulated myosin ATPase activity and depressed left ventricular developed pressure, cardiac contractility, and ventricular relaxation rates compared with BB nondiabetic littermates. These results suggest that the chronically diabetic state in the BB rat produces cardiac changes similar to those demonstrable after chemical diabetes induced by alloxan or STZ, or that seen during human diabetes mellitus.