Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whereas glucose is a major substrate for pulmonary lipid synthesis, fructose has also been suggested as a potential substrate. In vivo pulmonary fatty acid synthesis is depressed in hormonally deprived conditions, such as diabetes, and this can be modified by fructose feeding, but not by glucose feeding. In this study the glucose and fructose utilizations were compared in normal, diabetic and fasting states using isolated perfused rat lungs. When (U-14C)- or (5-3H)-glucose was used as substrate, glucose utilization by lung was reduced by 50% in both the fasting and diabetic animals compared to the normal controls. Using (U-14C)-glucose as substrate, the incorporation of (14C)-label in various metabolites of glucose was significantly depressed. For example, this reduction was 50% in lactate, pyruvate and CO2, 15% in ethanol-insoluble fraction, 65% in neutral lipids, 75% in phospholipids, 80% in fatty acid moiety, 40% in deacylated fraction and 10% in the polysaccharide fractions. Refeeding the fasted animals or insulin treatment to the diabetic animals restored these depressed (14C)-recoveries to the normal levels. Fructose utilization was less than 10% of glucose utilization, but remained unaffected by fasting and diabetic states. In addition, pulmonary hexokinase enzyme activity was lowered significantly in fasting and diabetic animals, whereas fructokinase enzyme activity was not altered. Despite the low rate of fructose utilization, these results suggest that fructose may serve as an alternative substrate for pulmonary phospholipid synthesis when glucose utilization is significantly depressed.
 ...
PMID:Nutritional and hormonal control of glucose and fructose utilization by lung. 390 22

Peripheral hyperinsulinemia may be associated with metabolic consequences that could contribute to the high incidence of macrovascular disease in patients with diabetes mellitus. Arterial wall and striated muscle cells were studied in dogs to examine the effect of hyperinsulinemia on the lipid content and on lipogenic and glycolytic enzyme activity. Eight pancreatectomized dogs received segmental pancreatic autografts with venous drainage into the iliac vein. Glucose disappearance rates (K values) were normal four years after transplantation, but both fasting serum insulin levels (48.9 +/- 4.8 v 11.8 +/- 1.9 microU/mL) and the total area under the glucose-insulin response curve (1797 +/- 196 v 1110 +/- 158 microU X min/mL) were significantly greater than in control animals (P less than 0.05). The hyperinsulinemic dogs had a marked triglyceride elevation in arterial smooth muscle (20.6 +/- 8.0 v 0.5 +/- 0.4 mumol/g) and striated muscle (171.4 +/- 46.6 v 41.2 +/- 7.7 mumol/g) (P less than 0.001). Moreover, key enzymes in lipid synthesis (glucose-6-phosphate dehydrogenase, malic enzyme, and 3-hydroxyacyl-CoA DH) were significantly increased (P less than 0.01) in the hyperinsulinemic animals, while the glycolytic enzymes, (phosphofructokinase, hexokinase, pyruvate kinase, and alpha-glycerophosphate DH) were not significantly different. These data demonstrate substantial enhancement of lipid synthesis in arterial wall and striated muscle in hyperinsulinemic dogs. Altered substrate metabolism in arterial walls, in association with hyperinsulinemia, may have important implications with regard to macrovascular disease in diabetes, particularly in insulin-treated patients. In addition, these studies may serve to stimulate longer term assessments of macroangiopathy in the increasing number of patients with functioning pancreatic allografts draining into the systemic circulation.
 ...
PMID:The effects of hyperinsulinemia on arterial wall and peripheral muscle metabolism in dogs. 390 54

Six men and three women with insulin-dependent diabetes (without complications) participated in physical training three times a week for 20 weeks. Physical training did not change the concentration of fasting blood-glucose, glucose excretion in urine or glucosylated haemoglobin (HbA1). However, the glucose disposal rate during euglycaemic clamp increased after training. In two patients a minor reduction of insulin dosage was necessary to alleviate slight hypoglycaemic episodes. The training resulted in significant increases in quadriceps isometric and dynamic strength and endurance. Maximal oxygen uptake increased by 8%, the activity of glycolytic enzymes in vastus lateralis muscle by 47% for hexokinase, and 30% for tri-osephosphate dehydrogenase and 25% for lactic dehydrogenase, the activity of oxidative enzymes by 42% for citrate synthase and 46% for 3-hydroxy-acyl-CoA-dehydrogenase. The glycogen concentration in the vastus lateralis muscle did not change significantly. Lipoprotein lipase activity did not change in muscle, nor in adipose tissue. The mean muscle fibre area increased by 25% and the area of FTa fibres by 30%. The new formation of capillaries around different muscle fibres was significant for FTb fibres (26%). The proliferation of capillaries, however, appeared to be insufficient to cope with the increased area of muscle fibres. As a result, the mean area of muscle fibre supplied by one capillary (a measure of diffusion distance) significantly increased after training for FTa fibres. It is concluded that with the exception of deficient proliferation of capillaries, patients with insulin-dependent diabetes mellitus show a normal central and peripheral adaptation to physical training. Physical training does not apparently improve blood glucose control in most cases, despite an increased insulin sensitivity.
 ...
PMID:Muscle adaptations and glucose control after physical training in insulin-dependent diabetes mellitus. 394 85

Enzymatic assays were modified to permit sensitive and highly reproducible simultaneous measurements of D-mannose and D-glucose in biological fluids during weeks 34-40 of human pregnancy. Plasma mannose and glucose averaged 9.8 +/- 0.4 (+/- SEM) and 790 +/- 16 micrograms/ml, respectively, after an overnight fast in pregnant women (n = 22) with normal carbohydrate metabolism. Significantly higher plasma mannose levels were found, despite only minor increases in plasma glucose, in pregnant women with relatively well controlled diabetes mellitus after an overnight fast (16.9 +/- 0.6 micrograms/ml mannose; 883 +/- 29 micrograms/ml glucose; n = 31) or 3-4 h after breakfast (15.7 +/- 1.2 micrograms/ml mannose; 1159 +/- 101 micrograms/ml glucose; n = 19). Plasma mannose correlated significantly with plasma glucose in the women with diabetes mellitus, particularly after an overnight fast. Samples of amniotic fluid were also obtained from the gravida with diabetes mellitus to provide some index of simultaneous relationships in utero. Amniotic fluid mannose and glucose averaged 5.9 +/- 0.4 and 302 +/- 24 micrograms/ml, respectively, after an overnight fast and 6.7 +/- 1.3 and 459 +/- 84 micrograms/ml 3-4 h after breakfast. In amniotic fluid, as in plasma, the concurrent levels of mannose and glucose conformed to relatively fixed relationships. Thus, both fetus and mother appear to be exposed to readily demonstrable amounts of mannose during late gestation and the absolute as well as relative abundance of mannose may be increased coincident with faulty maternal glucoregulation. However, since mannose did not exceed 3% of the concurrent concentration of glucose in any instance, it does not seem likely that endogenous levels of circulating mannose can modify glucose utilization appreciably by competing with glucose for phosphorylation via hexokinase and subsequent intracellular processing.
 ...
PMID:Relationships between glucose and mannose during late gestation in normal pregnancy and pregnancy complicated by diabetes mellitus: concurrent concentrations in maternal plasma and amniotic fluid. 395 33

The maximal activities of hexokinase and phosphofructokinase were measured in human adipose tissue. Though the mean activity of hexokinase was similar between a group of adult diabetics (n=24) and a group of non-diabetic controls (n=25), in the diabetic group the activity of phosphofructokinase was definitely reduced. Possibly this enzyme deficiency might contribute to impaired glucose utilization by the adipose cell in diabetes.
 ...
PMID:Glycolytic enzymes in adipose tissue of adult diabetics. 424 79

Activity of glucose-6-phosphate dehydrogenase in haematopoietic cells of bone marrow of rabbits was not affected during insular deficiency induced by starvation or alloxan diabetes as well as after intramuscular hydrocortisone administration. It is suggested that slight decrease in the activity of hexokinase detected during starvation and hydrocortisone administration might be accounted for by the presence of mature leukocytes in the population of isolated myelokaryocytes.
 ...
PMID:[Activity of hexokinase and glucose-6-phosphate dehydrogenase in hemopoietic cells of the bone marrow in normal rabbits and after hydrocortisone administration during starvation and alloxan diabetes]. 531 22

1. Insulin deficiency induced by anti-insulin serum or streptozotocin increased glucose absorption, as measured in everted sacs of rat upper ileum incubated for 30 min with oxygenated Krebs-Henseleit bicarbonate medium.2. Everted sacs prepared from the terminal ileum of insulin-deficient rats were able to accumulate glucose against a concentration gradient (i.e. development of active glucose transport).3. In experimental diabetes induced by streptozotocin, everted sacs of upper ileum showed increased 3-methyl glucose active transport, and sacs of terminal ileum showed development of 3-methyl glucose active transport.4. Lactic acid formation during the absorption of both glucose and 3-methyl glucose was increased approximately twofold in everted sacs of insulin-deficient animals.5. Insulin added at 100 mu./ml. to the incubating media of everted sacs prepared from insulin-deficient rats did not result in a reduction of glucose absorption or reverse the other effects.6. Fluoride (5 x 10(-3)M) added to the serosal and mucosal media of sacs of terminal ileum prepared from insulin-deficient rats decreased [(14)C]CO(2) formation from [U-(14)C]glucose and lactate formation during glucose absorption, but was unable to reverse the effect of insulin deficiency on glucose active transport.7. The effects of insulin deficiency induced by streptozotocin were more striking than those induced by anti-insulin serum.8. Everted sacs prepared from rats starved for 3 days showed increased glucose active transport accompanied by diminished conversion of [U-(14)C]glucose to [(14)C]CO(2).9. The possible role of hexokinase is discussed in relation to these findings.
 ...
PMID:The effect of insulin and insulin deficiency on the transport and metabolism of glucose by rat small intestine. 555 73

1. The overall metabolic changes in lactating mammary gland in alloxan-diabetic and anti-insulin-serum-treated rats were assessed by measurement of the incorporation of (14)C from specifically labelled glucose, pyruvate and acetate into carbon dioxide and lipid, together with measurements of enzymes concerned with the pentose phosphate pathway and with citrate metabolism. 2. Alloxan-diabetes depressed the rate of formation of (14)CO(2) from [1-(14)C]glucose and [2-(14)C]glucose to approx. 10% of the control rate; this was partially reversed by addition of insulin in vitro. The quotient Oxidation of [1-(14)C]glucose/Oxidation of [6-(14)C]glucose fell from a value of 17.6 in the control group to 3.9 in the diabetic group and was restored to 14.3 in the presence of insulin in vitro. In keeping with these results it was shown that glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were significantly decreased in alloxan-diabetic rats. 3. Alloxan-diabetes depressed the decarboxylation and the oxidation of labelled pyruvate, but not the oxidation of labelled acetate. 4. The synthesis of lipid from specifically labelled glucose was greatly decreased, that from [2-(14)C]pyruvate was almost unchanged and that from [1-(14)C]acetate alone was increased in alloxandiabetic rats. However, the stimulation of lipid synthesis from acetate by glucose was small in the alloxan-diabetic rats compared with the controls. Insulin in vitro partially reversed all these effects. Both citrate-cleavage enzyme and acetate thiokinase activities were decreased in alloxan-diabetic rats. 5. Treatment of rats with anti-insulin serum depressed the formation of (14)CO(2) from [1-(14)C]glucose and [2-(14)C]glucose, but increased that from [6-(14)C]glucose. This was completely restored by the presence of insulin in vitro. The quotient Oxidation of [1-(14)C]glucose/Oxidation of [6-(14)C]glucose fell from a value of 17.6 in the control group to 3.8 in the anti-insulin-serum-treated group. There were no changes in the activity of glucose 6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase, but the hexokinase distribution changed and the content of the soluble fraction increased significantly. 6. The synthesis of lipid from specifically labelled glucose was depressed in anti-insulin-serum-treated rats; this effect was completely reversed by addition of insulin in vitro to the tissue slices.
 ...
PMID:Effect of alloxan-diabetes and treatment with anti-insulin serum on pathways of glucose metabolism in lactating rat mammary gland. 569 42

1. Measurements were made of the non-oxidative reactions of the pentose phosphate cycle in liver (transketolase, transaldolase, ribulose 5-phosphate epimerase and ribose 5-phosphate isomerase activities) in a variety of hormonal and nutritional conditions. In addition, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were measured for comparison with the oxidative reactions of the cycle; hexokinase, glucokinase and phosphoglucose isomerase activities were also included. Starvation for 2 days caused significant lowering of activity of all the enzymes of the pentose phosphate cycle based on activity in the whole liver. Re-feeding with a high-carbohydrate diet restored all the enzyme activities to the range of the control values with the exception of that of glucose 6-phosphate dehydrogenase, which showed the well-known ;overshoot' effect. Re-feeding with a high-fat diet also restored the activities of all the enzymes of the pentose phosphate cycle and of hexokinase; glucokinase activity alone remained unchanged. Expressed as units/g. of liver or units/mg. of protein hexokinase, glucose 6-phosphate dehydrogenase, transketolase and pentose phosphate isomerase activities were unchanged by starvation; both 6-phosphogluconate dehydrogenase and ribulose 5-phosphate epimerase activities decreased faster than the liver weight or protein content. 2. Alloxan-diabetes resulted in a decrease of approx. 30-40% in the activities of 6-phosphogluconate dehydrogenase, ribose 5-phosphate isomerase, ribulose 5-phosphate epimerase and transketolase; in contrast with this glucose 6-phosphate dehydrogenase, transaldolase and phosphoglucose isomerase activities were unchanged. Treatment of alloxan-diabetic rats with protamine-zinc-insulin for 3 days caused a very marked increase to above normal levels of activity in all the enzymes of the pentose phosphate pathway except ribulose 5-phosphate epimerase, which was restored to the control value. Hexokinase activity was also raised by this treatment. After 7 days treatment of alloxan-diabetic rats with protamine-zinc-insulin the enzyme activities returned towards the control values. 3. In adrenalectomized rats the two most important changes were the rise in hexokinase activity and the fall in transketolase activity; in addition, ribulose 5-phosphate epimerase activity was also decreased. These effects were reversed by cortisone treatment. In addition, in cortisone-treated adrenalectomized rats glucokinase activity was significantly lower than the control value. 4. In thyroidectomized rats both ribose 5-phosphate isomerase and transketolase activities were decreased; in contrast with this transaldolase activity did not change significantly. Hypophysectomy caused a 50% fall in transketolase activity that was partially reversed by treatment with thyroxine and almost fully reversed by treatment with growth hormone for 8 days. 5. The results are discussed in relation to the hormonal control of the non-oxidative reactions of the pentose phosphate cycle, the marked changes in transketolase activity being particularly outstanding.
 ...
PMID:The pentose phosphate pathway of glucose metabolism. Hormonal and dietary control of the oxidative and non-oxidative reactions of the cycle in liver. 579 34

1. Measurements were made of the activities of the enzymes of the pentose phosphate pathway concerned in both the oxidative (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase) and the non-oxidative (ribose 5-phosphate isomerase, ribulose 5-phosphate epimerase, transketolase and transaldolase) reactions of this pathway, together with hexokinase and phosphoglucose isomerase, in adipose tissue in a variety of nutritional and hormonal conditions. 2. Starvation for 2 days caused a significant decrease in the activities of all the enzymes of the pentose phosphate pathway, with the exception of glucose 6-phosphate dehydrogenase, when expressed as activity/2 fat-pads; only the activities of ribose 5-phosphate isomerase and ribulose 5-phosphate epimerase were significantly decreased on the basis of activity/mg. of protein. Re-feeding with a high-carbohydrate or high-fat diet for 3 days restored the activity of all the enzymes of the pentose phosphate pathway to the range of the control values, with the exception of transketolase, which showed a marked ;overshoot' in rats re-fed with carbohydrate. Starvation for 3 days caused a marked decrease in the activities of glucose 6-phosphate dehydrogenase and transketolase. 3. On the basis of activity/two fat-pads, alloxan-diabetes caused a marked decrease, to about half the control value, in the activities of all the enzymes concerned in the pentose phosphate pathway, transketolase showing the smallest decrease; hexokinase and phosphoglucose isomerase activities were also decreased. Treatment with insulin for 3 and 7 days raised the activities to normal or supranormal values, transketolase showing the most marked ;overshoot' effect. On the basis of activity/mg. of protein the activity of none of the enzymes was significantly decreased in alloxan-diabetes; transketolase and transaldolase activities were raised above the control values. With insulin treatment for 3 or 7 days the activities of all the enzymes were significantly increased, except that of ribulose 5-phosphate epimerase at the shorter time-interval. Glucagon treatment did not alter any of the enzyme activities expressed on either basis. 4. Thyroidectomy caused a decrease of 30-40% in the activities of enzymes of the pentose phosphate pathway, except for transketolase activity, which fell to 50% of the control value. Little change occurred in adipose-tissue weight or protein content. 5. Adrenalectomy caused a decrease of 40% in the activity of glucose 6-phosphate dehydrogenase and of 20-30% in the activities of the remaining enzymes of the pentose phosphate pathway; hexokinase activity was also decreased. Treatment with cortisone for 3 days did not significantly raise the activity from that found in adrenalectomized rats. Treatment of normal rats with high doses of cortisone had no significant effect on the activities of the enzymes of the pentose phosphate pathway in adipose tissue. 6. The changes in enzyme activities are discussed in relation to: (a) the concept of constant-proportion groups of enzymes; (b) the known changes in the flux of glucose through alternative metabolic pathways; (c) the pattern of change found in liver with similar hormonal and dietary conditions.
 ...
PMID:The pentose phosphate pathway of glucose metabolism. Hormonal and dietary control of the oxidative nd non-oxidative reactions and related enzymes of the cycle in adipose tissue. 581 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>