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)

Ocimum sanctum (OS) has been mentioned in Indian system of traditional medicine to be of value in the treatment of diabetes mellitus. We have previously shown that OS shows a dose-dependent hypoglycemic effect and prevented rise in plasma glucose in normal rats. It also showed significant antihyperglycemic effect in STZ-induced diabetes. The present study was undertaken to assess the effect of OS on three important enzymes of carbohydrate metabolism [glucokinase (GK) (EC 2.7.1.2), hexokinase (HK) (EC 2.7.1.1) and phosphofructokinase (PFK) (EC 2.7.1.11)] along with glycogen content of insulin-dependent (skeletal muscle and liver) and insulin-independent tissues (kidneys and brain) in STZ (65 mg/kg) induced model of diabetes for 30 days. Administration of OS extract 200mg/kg for 30 days led to decrease in plasma glucose levels by approximately 9.06 and 26.4% on 15th and 30th day of the experiment. Liver and two-kidney weight expressed as percentage of body weight significantly increased in diabetics (P<0.0005) versus normal controls. OS significantly decreased renal (P<0.0005) but not liver weight. Renal glycogen content increased by over 10 folds while hepatic and skeletal muscle glycogen content decreased by 75 and 68% in diabetic controls versus controls. OS did not affect glycogen content in any tissue. Activity of HK, GK and PFK in diabetic controls was 35, 50 and 60% of the controls and OS partially corrected this alteration.
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PMID:Ethanolic extract of Ocimum sanctum leaves partially attenuates streptozotocin-induced alterations in glycogen content and carbohydrate metabolism in rats. 1469 24

In order to study the effects of chronic alcohol administration on the activities of the key glycolytic enzymes, a oral administration of alcohol solution in different concentrations was given to rats for 9 weeks. The activities of glucokinase (GK), phosphofructokinase (PFK) and hexokinase (HK) in liver were determined at the end of the study. The results showed that the activities of GK and PFK in the groups administrated with 30% and 50% alcohol solution decreased obviously in comparison with that in control group (P < 0.05). But the activity of HK had no significant differences in all five groups. Correlation analysis indicated that the activities of GK and PFK were correlated with the dose of alcohol significantly (r = -0.99(-)-0.97, P < 0.05). These results demonstrated that chronic alcohol administration can suppress the glycolytic pathway. They can also be one of the mechanisms of diabetes mellitus relating to alcohol because of the high blood sugar and the disturbed blood sugar regulation.
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PMID:[Effects of chronic alcohol administration on the activities of the key glycolytic enzymes of rats]. 1520 4

Glycolysis is important to cardiac metabolism and reduced glycolysis may contribute to diabetic cardiomyopathy. To understand its role independent of diabetes or hypoxic injury, we modulated glycolysis by cardiac-specific overexpression of kinase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (kd-PFK-2). PFK-2 controls the level of fructose 2,6-bisphosphate (Fru-2,6-P(2)), an important regulator of glycolysis. Transgenic mice had over 2-fold reduced levels of Fru-2,6-P(2). Heart weight/body weight ratio indicated mild hypertrophy. Sirius red staining for collagen was significantly increased. We observed a 2-fold elevation in glucose 6-phosphate and fructose 6-phosphate levels, whereas fructose 1,6-bisphosphate was reduced 2-fold. Pathways branching off of glycolysis above phosphofructokinase were activated as indicated by over 2-fold elevated UDP-N-acetylglucosamine and glycogen. The kd-PFK-2 transgene significantly inhibited glycolysis in perfused hearts. Insulin stimulation of metabolism and Akt phosphorylation were sharply reduced. In addition, contractility of isolated cardiomyocytes was impaired during basal and hypoxic incubations. The present study shows that cardiac overexpression of kinase-deficient PFK-2 reduces cardiac glycolysis that produced negative consequences to the heart including hypertrophy, fibrosis, and reduced cardiomyocyte function. In addition, metabolic and signaling responses to insulin were significantly decreased.
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PMID:Cardiac expression of kinase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase inhibits glycolysis, promotes hypertrophy, impairs myocyte function, and reduces insulin sensitivity. 1533 93

The skin cells chiefly depend on carbohydrate metabolism for their energy requirement during cutaneous wound healing. Since the glucose metabolism is greatly hampered in diabetes and this might affect wound repair process. This prompted us to investigate the intermediate steps of energy metabolism by measuring enzyme activities in the wound tissues of normal and streptozotocin-induced diabetic rats following excision-type of cutaneous injury. The activities of key regulatory enzymes namely hexokinase (HK), phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and glucose-6 phosphate dehydrogenase (G6PD) have been monitored in the granulation tissues of normal and diabetic rats at different time points (2, 7, 14 and 21 days) of postwounding. Interestingly, a significant alteration in all these enzyme activities was observed in diabetic rats. The activity of PFK was increased but HK, LDH and CS showed a decreased activity in the wound tissue of diabetics as compared to normal rats. However G6PD exhibited an elevated activity only at early stage of healing in diabetic rats. Thus, the results suggest that significant alterations in the activities of energy metabolizing enzymes in the wound tissue of diabetic rats may affect the energy availability for cellular activity needed for repair process and this may perhaps be one of the factor responsible for impaired healing in these subjects.
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PMID:Energy metabolism in the granulation tissue of diabetic rats during cutaneous wound healing. 1579 55

Obesity is one of the most serious threats to human health today. Although there is general agreement that environmental factors such as diet have largely caused the current obesity pandemic, the environmental changes have not affected all individuals equally. To model gene-by-environment interactions in a mouse model system, our group has generated an F(16) advanced intercross line (AIL) from the SM/J and LG/J inbred strains. Half of our sample was fed a low-fat (15% energy from fat) diet while the other half was fed a high-fat (43% energy from fat) diet. The sample was assayed for a variety of obesity- and diabetes-related phenotypes such as growth rate, response to glucose challenge, organ and fat pad weights, and serum lipids and insulin. An examination in the F(16) sample of eight adiposity quantitative trait loci previously identified in an F(2) intercross of SM/J and LG/J mouse strains reveals locus-by-diet interactions for all previously mapped loci. Adip7, located on proximal chromosome 13, demonstrated the most interactions and therefore was selected for fine mapping with microsatellite markers. Three phenotypic traits, liver weight in male animals, serum insulin in male animals, and reproductive fat pad weight, show locus-by-diet interactions in the 127-kb region between markers D13Mit1 and D13Mit302. The phosphofructokinase (PFK) C (Pfkp) and the pitrilysin metalloprotease 1 (Pitrm1) genes are compelling positional candidate genes in this region that show coding sequence differences between the parental strains in functional domains.
Diabetes 2005 Jun
PMID:Fine-mapping gene-by-diet interactions on chromosome 13 in a LG/J x SM/J murine model of obesity. 1591 10

Several studies have shown impairment of neutrophil function, a disorder that contributes to the high incidence of infections in diabetes. Since glucose and glutamine play a key role in neutrophil function, we investigated their metabolism in neutrophils obtained from the peritoneal cavity of streptozotocin-induced diabetic rats. The activities of hexokinase, glucose-6-phosphate dehydrogenase (G6PDH), phosphofructokinase (PFK), citrate synthase, phosphate-dependent glutaminase, NAD+-linked and NADP+-linked isocitrate dehydrogenase were assayed. Glucose, glutamine, lactate, glutamate and aspartate, and the decarboxylation of [U-14C], [1-14C] and [6-14C]glucose; [U-14C]palmitic acid; and [U-14C]glutamine were measured in 1-h incubated neutrophils. Phagocytosis capacity and hydrogen peroxide (H2O2) production were also determined. All measurements were carried out in neutrophils from control, diabetic and insulin-treated (2-4 IU/day) diabetic rats. Phagocytosis and phorbol myristate acetate (PMA)-stimulated H2O2 production were decreased in neutrophils from diabetic rats. The activities of G6PDH and glutaminase were decreased, whereas that of PFK was raised by the diabetic state. The activities of the remaining enzymes were not changed. Diabetes decreased the decarboxylation of [1-14C]glucose and [U-14C]glutamine; however, [6-14C]glucose and [U-14C]palmitic acid decarboxylation was increased. These observations indicate that changes in metabolism may play an important role in the impaired neutrophil function observed in diabetes. The treatment with insulin abolished the changes induced by the diabetic state even with no marked change in glycemia. Therefore, insulin may have a direct effect on neutrophil metabolism and function.
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PMID:Diabetes causes marked changes in function and metabolism of rat neutrophils. 1646 55

Carbohydrate metabolism is impaired in diabetes. The resultant hyperglycemia could cause tremendous changes in the metabolic activities of the liver. We therefore designed this study to investigate the effects of caloric restriction, which has been shown to improve blood glucose homeostasis, on carbohydrate metabolism in the livers of non-diabetic and streptozotocin-induced diabetic rats. Forty male Wistar rats were divided into two groups of caloric restricted (CR) and ad libitum (AL) fed rats. The caloric restricted animals were subjected to 30% caloric restriction. Feeding experiments were conducted for 9 weeks before the induction of diabetes in 50% of the groups. Caloric restriction was found to significantly decrease glycogen (p<0.001), hepatic glucose (p<0.01), phosphofructokinase (p<0.05), glucokinase (p<0.05), aldose reductase (p<0.05), and sorbitol dehydrogenase (p<0.05) and significantly increase hexokinase (p<0.001), glucose-6-phosphate dehydrogenase (p<0.05), and glucose-6-phosphatase activities (p<0.05) in diabetic and non-diabetic rats. From our results, it is suggested that alteration of the metabolic pathways involved in glucose metabolism in the liver could be one of the various ways in which CR attenuates hyperglycemic effects in diabetes.
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PMID:Modulation of the flux patterns in carbohydrate metabolism in the livers of streptozoticin-induced diabetic rats by dietary caloric restriction. 1674 Mar 92

Although the influence of diabetes on salivary glands is well studied, it still presents conflicting results. In this work, the regulation of the phosphofructokinase-1 enzyme (PFK-1) was studied utilizing the salivary glands of rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (60 mg/Kg of body weight) in rats (180-200 g). The animals were killed 30 days after the induction of diabetes and the submandibular and parotid salivary glands were used. Hyperglycemia was evaluated by blood sugar determination. The distribution of PFK-1 between the soluble and cytoskeleton fractions, the phosphate content of PFK-1, the content of fructose-2,6-bisphosphate and the activity of the PFK-2 enzyme were determined. The calculated relative glandular weight showed a higher value for the parotid gland in comparison with the control, but not for the submandibular gland. The activity of PFK-1 expressed per gland showed no variation between diabetic and control animals. However, considering the specific activity, the soluble enzyme presented a value 50% higher than that of the control and the cytoskeleton bound form increased by 84% compared to the control. For the parotid gland, no difference in the specific activity between diabetic and control animals was observed. On the other hand, the activity per gland of the soluble enzyme increased in the diabetic animals. The phosphate content of PFK-1 increased in the submandibular and parotid glands of diabetic rats. Both the content of fructose-2,6-bisphosphate and the active form of PFK-2 were reduced in the diabetic glands. In conclusion, the increase in the activity of PFK-1 observed in the salivary glands of rats with streptozotocin-induced diabetes does not seem to be due to its modulator fructose-2,6-bisphosphate.
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PMID:Activity, distribution and regulation of phosphofructokinase in salivary gland of rats with streptozotocin-induced diabetes. 1687 2

The present study was undertaken to assess the effect of Helicteres isora L. on four important enzymes of carbohydrate metabolism (glucokinase [GK], hexokinase [HK] phosphofructokinase [PFK] and fructose-1, 6-bisphosphatase [FBP]) along with glycogen content of insulin-dependent (skeletal muscle and liver) and insulin-independent tissues (kidneys and brain) in streptozotocin (STZ; 60 mg/kg)-induced model of diabetes for 30 days. Administration of bark extracts (100, 200 mg/kg) for 30 days led to decrease in plasma glucose levels by approximately 9.60% and 22.04% and 19.18% and 33.93% on 15th and 30th day, respectively, of the experiment. Liver and two-kidney weight expressed as percentage of body weight significantly increased in diabetics (P < 0.05) versus normal controls. Renal glycogen content increased by 10 folds while hepatic and skeletal muscle glycogen content decreased by 75% and 68% in diabetic controls versus controls. H. isora did not affect glycogen content in any tissue. The decreased activities of PFK, GK, FBP and HK in diabetic controls were 40%, 50%, 50% and 60% and bark extract of H. isora partially corrected this alteration. The efficacy of the bark extract was comparable with Tolbutamide, a well-known hypoglycemic drug.
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PMID:Attenuation of Helicteres isora L. bark extracts on streptozotocin-induced alterations in glycogen and carbohydrate metabolism in albino rats. 1981 19

Cassia auriculata traditionally has been used to treat diabetes from ancient times. The objective of the present study was to investigate the mechanism of action for the antidiabetic activity of aqueous leaf extract of C. auriculata (CLEt) in streptozotocin-induced mildly diabetic (MD) and severely diabetic (SD) rats. CLEt was orally administered to MD and SD rats at a dose of 400 mg/kg once a day for 15 days. CLEt-treated MD and SD rats showed significant reduction in fasting blood glucose. Assessment of plasma insulin and C-peptide following treatment with CLEt revealed significant elevation in their levels. Administration of CLEt enhanced the activity of hepatic hexokinase and phosphofructokinase and suppressed glucose-6-phosphatase and fructose-1,6-bisphosphatase in both MD and SD rats. A significant rise in glycogen content was also observed in both liver and muscles of CLEt-fed MD and SD rats. Histopathological examination of pancreatic sections revealed increased number of islets and beta-cells in CLEt-treated MD as well as SD rats. The findings of the study suggest that the antidiabetic effect of CLEt could be due to its insulinogenic action. In addition, impaired glucose homeostasis was improved by feeding the extract through amelioration in the carbohydrate metabolic pathways. Thus, the extract may exert an antidiabetic effect through pancreatic as well as extrapancreatic action.
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PMID:Elucidation of mechanism of action of Cassia auriculata leaf extract for its antidiabetic activity in streptozotocin-induced diabetic rats. 2052 78


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