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)

The thiazolidinediones are a class of novel antidiabetic compounds that enhance the response of target tissues to insulin. Pioglitazone, a thiazolidinedione analog, lowers blood glucose and insulin levels in rodent models of non-insulin-dependent diabetes mellitus. We have studied the effect of pioglitazone on 3T3-L1 cells, a cell line that undergoes differentiation from a preadipocyte fibroblastic morphology to that of an adipocyte. Pioglitazone treatment of preadipocytes enhanced the insulin- or insulin-like growth factor-1 (IGF-I)-regulated differentiation (monitored by the rate of lipogenesis or triglyceride accumulation), whereas treatment of the cells in the absence of insulin or IGF-I resulted in no apparent change in the cellular phenotype. Pioglitazone caused both a leftward shift and enhanced maximum response for the IGF-I-regulated differentiation of the cells, consistent with the idea that the drug enhances the sensitivity of cells to polypeptide hormones. A series of pioglitazone analogs were tested in this system, and variations in activity relative to that of the parent compound were observed. A study of the time required for the drug to exert an effect on differentiation revealed that an increased rate of lipogenesis occurred 16-24 hr after drug treatment in appropriately staged cells. An increased rate of glucose transport and increased activity of lipogenic enzymes were noted in a time frame that correlated with the change in lipogenesis. Analysis of mRNA abundance for Glut-4, lipoprotein lipase, and glucose-6-phosphate dehydrogenase showed that pioglitazone enhanced the insulin induction of these mRNA species. Thus, pioglitazone, in combination with insulin or IGF-I, appears to be exerting effects on the cellular phenotype by eliciting changes in the expression of genes that regulate metabolic pathways leading to the acquisition of the differentiated phenotype.
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PMID:Enhancement of adipocyte differentiation by an insulin-sensitizing agent. 153 16

Sammo plant which is traditionally used in Egypt for the treatment of diabetes mellitus, was administered at low and high levels (4% and 8% respectively at the expense of starch) to adult male alloxanized albino rats, to study its effect on energy metabolism. Adenosine-5-triphosphate (ATP) in the brain (B), liver (L) and kidneys (K) organs of alloxanized rats was significantly lowered compared with the negative control. On the other hand, adenosine-5-diphosphate (ADP) and adenosine-5-monophosphate (AMP) contents in the same organs were elevated markedly. In this connection myokinase activity in cytoplasmic and mitochondrial fractions of B, L and K organs was stimulated at control. Also, the activities of some fundamental enzymes of the oxidative pentose phosphate pathway i.e. glucose-6-phosphate dehydrogenase (G-6-PD) and 6-phospho-gluconate dehydrogenase (6-PGD) in cytoplasmic and mitochondrial fractions of the same organs were markedly increased. Administration of Sammo at low and high levels reduced the consumption of ATP in B, L and K organs relative to positive control. Whereas, ADP and AMP contents were relatively reduced. Also, myokinase activity in the same organs were relatively inhibited. The activity of G-6-PD and 6-PGD in cytoplasmic and mitochondrial fractions of the same organs were also decreased relative to the positive control.
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PMID:The effect of sammo administration on some fundamental enzymes of pentose phosphate pathway and energy metabolites of alloxanized rats. 157 54

This hospital-based study demonstrates a statistically significant higher prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among the Saudi patients with diabetes mellitus (12.4%) as compared to healthy population controls (2.0%) (p less than 0.008). The nature of this association is difficult to explain. In view of a higher frequency of G6PD deficiency among diabetics, it is suggested that all patients with diabetes be screened for this enzymopathy in order to avoid the use of certain drugs or toxic agents that can produce hemolysis.
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PMID:Glucose-6-phosphate dehydrogenase deficiency and diabetes mellitus. 177 4

A mathematical model is designed for the metabolism of D-glucose in erythrocytes under conditions in which the flux through the pentose phosphate pathway accounts for either 5% or 75% of the rate of D-glucose phosphorylation, as indeed observed in the absence or presence of menadione. This model allows to compare the fate of D-[1-1H]glucose and D-[1-2H]glucose, taking into account the isotopic discrimination towards the deuterated hexose in the reactions catalyzed by phosphoglucoisomerase and glucose-6-phosphate dehydrogenase. The study of this model is extended to the fate of tracer amounts of either D-[1-14C]glucose, D-[U-14C]glucose or D-[1-3H]glucose mixed with non-radioactive D-[1-1H]glucose or D-[1-2H]glucose. The fates of D-[1-14C, 1-2H]glucose and D-[U-14C, 1-2H]glucose in this model are also examined. A fair agreement between the data derived from the mathematical model and prior experimental findings is observed, at least as far as the fate of 14C-labelled D-glucose is concerned. The present study illustrates, therefore, the mechanism by which unequal isotopic discrimination in different enzymatic reactions may cause severe misjudgment of metabolic flow when using deuterated and/or tritiated D-glucose as substitute and/or tracer for the protonated hexose.
Diabetes Res 1991 Sep
PMID:Modelling of isotopic discrimination in intact cells. 182 43

The effect of long-term (12 weeks) oral treatment with sodium orthovanadate on hepatic glycogen metabolizing and lipogenic enzymes was studied in genetically diabetic db/db mice. These mice were characterized by significant (P less than .001) obesity, hyperglycemia, and hyperinsulinemia. Vanadate administration led to significant decreases in body weight (P less than .001) and plasma insulin levels (P less than .01) and the mice became normoglycemic. The total glycogen synthase (EC 2.4.1.11) activity in the livers of diabetic mice showed a 47% increase, which did not undergo any significant change after treatment with vanadate. Hepatic phosphorylase (EC 2.4.1.1) activities (a and total) showed twofold increases in db/db mice when compared with the nondiabetic ones. Vanadate caused significant decreases in phosphorylase a (P less than .02) and total phosphorylase (P less than .001) activities. Glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and malic enzyme (EC 1.1.1.40) in diabetic liver had differential alterations, as indicated by a 50% decrease in glucose-6-phosphate dehydrogenase and 160% increase in malic enzyme activities. Vanadate administration led to normalization of both enzyme activities. In nondiabetic mice, vanadate treatment did not cause changes in any parameter, except for a 46% decrease in plasma insulin levels. This investigation indicates that vanadate can normalize many of the metabolic abnormalities seen in the liver of genetically diabetic db/db mice, a model for non-insulin-dependent diabetes mellitus (NIDDM). Vanadate also causes a decrease in plasma insulin level, along with normalization of plasma glucose, which suggests a partial reversal of insulin resistance.
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PMID:Long-term effects of vanadate treatment on glycogen metabolizing and lipogenic enzymes of liver in genetically diabetic (db/db) mice. 191 Jan 43

The effect of glucose concentration and insulin on glucose incorporation was studied in primary cultures of rat hepatocytes. The rate of glucose incorporation into hepatocytes was proportional to the medium glucose concentration from 100 to 800 mg/dl. At 800 mg/dl glucose the rate reached a plateau. Of the glucose taken up by hepatocytes, 16 and 18% was incorporated into glycogen and lipid, respectively, and 58% into the nucleotide fraction after incubation for 4 h. In the medium, lactate was the major product found. Insulin stimulates glucose incorporation by 20-112% into all the above pathways at glucose concentrations between 100 and 800 mg/dl. The insulin effect was noted as early as 2-4 h (early effect) and up to 24 h (delayed effect). This effect of insulin was observed to be dose dependent from 5 to 200 ng/ml insulin. While the delayed insulin effect was abolished by cycloheximide, the early effect of insulin was not affected. With respect to the key enzyme activities of glucose utilization, activation of glycogen synthase (increase of I-activity/total activity) and pyruvate kinase (activation at 0.2 mM phosphoenolpyruvate) was noted 4 h after insulin addition, and these effects were not abolished by cycloheximide. These two enzymes increased in total activity after 24 h. Both glucokinase and glucose-6-phosphate dehydrogenase activities increased by 30-35% and 65-93% at 4 and 24 h, respectively. The results indicate that hepatocytes directly utilize glucose in a dose-dependent manner with respect to glucose and insulin. A major early and delayed effect of insulin appeared due to the activation and induction of the key hepatic enzymes of glucose utilization, respectively.
Diabetes Res Clin Pract 1991 Sep
PMID:In vitro stimulation of glucose utilization by insulin in primary cultures of rat hepatocytes. 195 79

The effect of a long-acting somatostatin analogue on the acute renal hypertrophy following induction of experimental diabetes in the rat has been studied. The kidney weight increase occurring at 2 and 7 days after alloxan injection was significantly lower in the diabetic group receiving somatostatin. Similarly, the previously reported increase in glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (EC 1.1.1.44) found in the kidney at 2 and 7 days of diabetes was less marked in the group receiving SMS 201-995. The fall in renal phosphoribosyl pyrophosphate associated with early diabetic renal hypertrophy (7) was also lessened by administration of SMS 201-995. No effects of the drug were found in the normal rat on the same regimen of treatment. These observations indicate involvement of glucagon and/or growth hormone in the initiation of kidney growth in diabetes.
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PMID:The effect of a somatostatin analogue (SMS 201-995, Sandostatin) on the concentration of phosphoribosyl pyrophosphate and the activity of the pentose phosphate pathway in the early renal hypertrophy of experimental diabetes in the rat. 245 25

Activities of hexokinase and glucose-6-phosphate dehydrogenase have been measured in red blood cells from control, diabetic and insulin treated rats. After an initial decrease, the enzyme activities increased, but remained lower than control levels. A reversal of the diabetes effect was seen with insulin administration. Insulin induced hypoglycemia increased both enzymes. An overall control of glucose metabolism by insulin in red blood cells was observed.
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PMID:Effect of diabetes and insulin-induced hypoglycemia on hexokinase and glucose-6-phosphate dehydrogenase in red blood cells. 267 46

The effects of vitamin B6 on erythrocyte metabolism, erythrocyte hemoglobin O2 affinity (P50), and nonenzymatic glycosylation were studied in 15 Caucasian men with type II (non-insulin-dependent) diabetes mellitus. A control group of 13 healthy Caucasian men was also evaluated. Before treatment, diabetic subjects had low mean cell hemoglobin concentration values and increases in both erythrocyte 2,3-diphosphoglycerate (2,3-DPG) levels and erythrocyte hexokinase activities. Although all three of these changes are associated with a decrease in hemoglobin O2 (Hb-O2) affinity, P50 values were normal in diabetic subjects. Moreover, P50 values normalized to pH 7.4 (P50(7.4] were inversely related to the level of glycosylated hemoglobin (HbA1c). Both erythrocyte 2,3-DPG and erythrocyte ATP were also inversely related to HbA1c. Vitamin B6 nutriture, as determined by erythrocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, was normal in all diabetic subjects before vitamin B6 therapy. Nonetheless, HbA1c levels decreased after 6 wk of treatment with 150 mg/day pyridoxine and increased again during placebo administration. These changes were not explained by changes in fasting blood glucose. Pyridoxine therapy also decreased P50(7.4) values and increased erythrocyte AST and ALT activities but had no effect on 2,3-DPG, ATP, or the activities of hexokinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. These observations suggest that 1) nonenzymatic glycosylation may play a role in regulating both erythrocyte metabolism and Hb-O2 affinity in diabetic subjects, and 2) vitamin B6 therapy may modify nonenzymatic glycosylation of hemoglobin in this population.
Diabetes 1989 Jul
PMID:Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus. 273 64

The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency was estimated in 318 diabetic patients using Beulter's fluorescent Spot test. A significantly (p less than 0.001) higher prevalence of G6PD deficiency was detected among diabetic patients (19.6%) as compared to controls (10.4%). The distribution of G6PD deficiency varied with age, sex, and duration of diabetes. Among diabetic men, the prevalence of deficiency was significantly higher than controls in both age groups; 40 years and below, and 41 years and above (p less than 0.005 and p less than 0.02, respectively). Among diabetic women, the significantly higher prevalence of deficiency was observed only in the young age group (p less than 0.005), whereas the difference among the older age group was not significant (p greater than 0.1). A significant increase in the prevalence of deficiency with increase in duration of diabetes was detected among men (p less than 0.05), but not in women. The results of the study suggest a positive association between G6PD deficiency and diabetes mellitus.
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PMID:Association of glucose-6-phosphate dehydrogenase deficiency with diabetes mellitus. 295 93


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