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)

To examine the mechanisms of hyperglycemia-induced insulin resistance, eight insulin-dependent (type I) diabetic men were studied twice, after 24 h of hyperglycemia (mean blood glucose 20.0 +/- 0.3 mM, i.v. glucose) and after 24 h of normoglycemia (7.1 +/- 0.4 mM, saline) while receiving identical diets and insulin doses. Whole-body and forearm glucose uptake were determined during a 300-min insulin infusion (serum free insulin 359 +/- 22 and 373 +/- 29 pM, after hyper- and normoglycemia, respectively). Muscle biopsies were taken before and at the end of the 300-min insulin infusion. Plasma glucose levels were maintained constant during the 300-min period by keeping glucose for 150 min at 16.7 +/- 0.1 mM after 24-h hyperglycemia and increasing it to 16.5 +/- 0.1 mM after normoglycemia and by allowing it thereafter to decrease in both studies to normoglycemia. During the normoglycemic period (240-300 min), total glucose uptake (25.0 +/- 2.8 vs. 33.8 +/- 3.9 mumol.kg-1 body wt.min-1, P less than 0.05) was 26% lower, forearm glucose uptake (11 +/- 4 vs. 18 +/- 3 mumol.kg-1 forearm.min-1, P less than 0.05) was 35% lower, and nonoxidative glucose disposal (8.9 +/- 2.2 vs. 19.4 +/- 3.3 mumol.kg-1 body wt-1min-1, P less than 0.01) was 54% lower after 24 h of hyper- and normoglycemia, respectively. Glucose oxidation rates were similar. Basal muscle glycogen content was similar after 24 h of hyperglycemia (234 +/- 23 mmol/kg dry muscle) and normoglycemia (238 +/- 22 mmol/kg dry muscle). Insulin increased muscle glycogen to 273 +/- 22 mmol/kg dry muscle after 24 h of hyperglycemia and to 296 +/- 33 mmol/kg dry muscle after normoglycemia (P less than 0.05 vs. 0 min for both). Muscle ATP, free glucose, glucose-6-phosphate, and fructose-6-phosphate concentrations were similar after both 24-h treatment periods and did not change in response to insulin. We conclude that a marked decrease in whole-body, muscle, and nonoxidative glucose disposal can be induced by hyperglycemia alone.
Diabetes 1992 May
PMID:Mechanisms of hyperglycemia-induced insulin resistance in whole body and skeletal muscle of type I diabetic patients. 156 26

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

We experienced 41 cases of Cushing's syndrome (12 males and 29 females, 15 years old - 65 years old) during the last 20 years. These included 20 patients with unilateral adrenal adenoma (Cushing's syndrome), 19 patients with bilateral adrenal hyperplasia (Cushing's disease), one patient with adrenal carcinoma and one patient with primary adrenocortical nodular dysplasia (PAND). Moreover, these cases included some special ones, i.e. 5 cases with destructive thyroiditis after treatment, 2 cases with aggravation of arthritis after treatment, a case of Carney's complex with PAND, one case with paradoxical response to dexamethasone, and one case combined with empty sella syndrome. The most specific clinical signs were moon face (95% occurrence), hypertension (95%) and subcutaneous bruising (80%). Other significant signs were eye edema (66%), buffalo hump (68%), subcutaneous purpura (63%) and osteoporosis (49%). Skin striae was not a common sign in our cases (41%). Renal stone was observed in only 20% of our patients but was a significant sign in this syndrome. There was no difference in the occurrence of each clinical sign between Cushing's syndrome and Cushing's disease. The elevation of white blood cell count (WBC) and serum sodium, a decrease of serum potassium, and a decrease of reabsorption of phosphate (%TRP) were observed. Thyroid-stimulating hormone (TSH) and human growth hormone (HGH) were suppressed in patients with Cushing's syndrome and patients with Cushing's disease. These results were consistent with those of previous reports. However, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) were high in those patients with Cushing's syndrome and those with Cushing's disease. Oral glucose tolerance test was carried out in 34 patients before and after treatment. Thirty-one percent of those had diabetes mellitus and 26% had impaired glucose tolerance (IGT). The response of IRI in this test was high in patients with Cushing's syndrome and patients with Cushing's disease, and decreased 4 weeks after treatment in those with Cushing's syndrome but remained high in those with Cushing's disease. Plasma ACTH level and urinary 17-OHCS excretion were significantly higher in Cushing's disease than in Cushing's syndrome. During an 8mg-high-dose dexamethasone suppression test, urinary 17-OHCS excretion in 13 of 14 patients with Cushing's disease (93%) was suppressed by more than 50% of baseline on the second day of testing. However, all of 18 patients with Cushing's syndrome, who had an 8mg-dexamethasone suppression test, failed to suppress urinary 17-OHCS by 50% of baseline.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Forty-one cases of Cushing's syndrome: a comparison between Cushing's syndrome (adrenal adenoma) and Cushing's disease (adrenal hyperplasia)]. 163 31

The concentration of fructose 2,6-bisphosphate in the brain remained stable during starvation and early stages of ischaemia, but decreased in diabetes or after lengthened ischaemia. 6-Phosphofructo-1-kinase activity was also decreased in diabetic and ischaemic animals, whereas 6-phosphofructo-2-kinase was not modified. The concentration of the bisphosphorylated metabolite seems to be remarkably constant under a wide variety of experimental conditions, suggesting that it plays an essential role in the basal activation of 6-phosphofructo-1-kinase. Purified 6-phosphofructo-2-kinase also showed fructose-2,6-bisphosphatase activity with an activity ratio similar to that of the purified heart isoenzyme. The brain enzyme also has a net charge similar to that of the heart isoenzyme. Its activity is not modified by sn-glycerol 3-phosphate, and it is more sensitive to citrate than the liver or muscle isoenzyme. Moreover, the enzyme from brain, similarly to that from heart and muscle, is not modified by the cyclic AMP-dependent protein kinase or protein kinase C. A near-full-length cDNA probe from liver hybridized with RNA from brain and heart. In both cases, a major band of 6.8 kb of RNA and a minor one of 4 kb of RNA were detected. All these properties support the hypothesis that brain contains a different isoenzymic form from that of liver and muscle, and it is probably related to the heart isoform.
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PMID:6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in rat brain. 164 1

5-Amino-4-imidazolecarboxamide (AICA) riboside, the nucleoside corresponding to AICA ribotide (AICAR or ZMP), an intermediate of the de novo pathway of purine biosynthesis, was found to exert a dose-dependent inhibition on gluconeogenesis in isolated rat hepatocytes. Production of glucose from lactate-pyruvate mixtures was half-maximally inhibited by approximately 100 microM and completely suppressed by 500 microM AICA riboside. AICA riboside also inhibited the production of glucose from all other gluconeogenic precursors investigated, i.e., fructose, dihydroxyacetone, and L-proline. Measurements of intermediates of the glycolytic-gluconeogenic pathway showed that AICA riboside provoked elevations of triose phosphates and fructose-1,6-bisphosphate and decreases in fructose-6-phosphate and glucose-6-phosphate. The effects of AICA riboside persisted when the cells were washed 10 min after its addition but were suppressed by 5-iodotubercidin, an inhibitor of adenosine kinase. AICA riboside provoked a dose-dependent buildup of normally undetectable Z nucleotides. After 20 min of incubation with 500 microM AICA riboside, ZMP, ZTP, and ZDP reached 3, 0.3, and 0.1 mumol/g cells, respectively. Concentrations of ATP were not significantly modified by addition of up to 500 microM AICA riboside when the cells were incubated with lactate-pyruvate but decreased with fructose or dihydroxyacetone. The activity of rat liver fructose-1,6-bisphosphatase was inhibited by ZMP with an apparent Ki of 370 microM. It is concluded that AICA riboside exerts a suppressive effect on gluconeogenesis because it provokes an accumulation of ZMP, which inhibits fructose-1,6-bisphosphatase.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Oct
PMID:Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes. 165 65

We evaluated thrombin-induced inositol phosphate accumulation in [3H]inositol-labeled platelets prepared from patients with non-insulin-dependent diabetes mellitus. There were no significant differences in [3H]inositol incorporation into and contents of phosphoinositides between the diabetic patients and their age-matched control subjects. Thrombin induced a dose- and time-dependent accumulation of inositol phosphate. The accumulation of [3H]inositol trisphosphate and [3H]inositol bisphosphate by thrombin stimulation were significantly enhanced in platelets from the diabetic patients, although the accumulation of [3H]inositol monophosphate did not differ between the diabetic patients and the control subjects. In addition, the platelet aggregation rate induced by thrombin was also significantly enhanced in the diabetic patients in correlation with the enhanced inositol phosphate accumulation. These results suggest that increased inositol phosphate accumulation may cause accelerated platelet functions in diabetes mellitus.
Diabetes Res Clin Pract 1991 Oct
PMID:Increased inositol phosphate accumulation in platelets from patients with NIDDM. 166 Aug 5

Aldose reductase (EC 1.1.1.21) is implicated in the pathophysiology of diabetic complications. In this paper we determined the activities of aldose reductase and ATPases of the erythrocytes in 17 patients with Type 2 (non-insulin-dependent) diabetes mellitus (NIDDM). In the aldose reductase assay we used fluorometric method to avoid the disturbance of hemoglobin. With dihydronicotinamide adenine dinucleotide (NADH), we verified it was aldose reductase but not aldehyde reductase II that was activated in the erythrocytes of the patients with NIDDM. The aldose reductase activity of the erythrocytes in the patients was significantly higher (P less than 0.01) than that in the controls. The activity of Na+/K(+)-ATPase of the patients was significantly lower (P less than 0.01) than that of the controls. The activities of Ca(2+)-ATPase and Mg(2+)-ATPase on the erythrocyte membranes of the patients were similar to those of the controls. At the same time we measured the seven nucleotide concentrations in the erythrocytes of the patients. In this experiment we used ultrafiltration method, instead of acid precipitation to make it possible to determine dihydronicotinamide adenine dinucleotide phosphate (NADPH) and NADH. The concentrations of ATP, ADP and AMP were similar to those of the controls. The concentrations of NADPH, NAD+ and NADH in the erythrocytes of the patients were significantly lower (P less than 0.01, 0.05 and 0.05 respectively) than those of controls. The concentration of nicotinamide adenine dinucleotide phosphate (NADP+) in the patients was significantly higher (P less than 0.01) than that of controls.
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PMID:Activities of aldose reductase, ATPases, and nucleotide concentrations of erythrocytes in patients with type 2 (non-insulin-dependent) diabetes mellitus. 166 Dec 22

Na(+)-K(+)-ATPase provides the driving force for cellular Na+ transport and exists in multiple isoforms that differ in ouabain sensitivities. We report that the Ki for ouabain inhibition of glucose-evoked short-circuit current, determined in intact rat ileal mucosa mounted in Ussing chambers, is higher in streptozocin-induced chronically diabetic rats than in age-matched controls. The changes in ouabain sensitivity seen in diabetes also occurred when intact ileum of age-matched controls was incubated in vitro with 2.8 x 10(-5) M glucagon for at least 80 min. The effect of glucagon was blocked by cycloheximide, indicating a role for protein synthesis. This suggests that changes in ouabain sensitivity seen in diabetes are produced by glucagon, the serum concentration of which increases in diabetes. Ouabain-dependent phosphorylation of Na(+)-K(+)-ATPase (backdoor phosphorylation) revealed a higher Km for phosphate in intestinal basolateral membranes obtained from diabetic rats compared with age-matched controls, again confirming a decrease in ouabain sensitivity. Furthermore, the mRNA encoding the alpha 1-isoform was upregulated 2.6-fold in chronically diabetic intestines. This suggests that the ouabain sensitivity seen during diabetes may be due to upregulation of the alpha 1-isoform, known to be less sensitive to ouabain than the other isoforms.
Diabetes 1991 Dec
PMID:Diabetes mellitus and glucagon alter ouabain-sensitive Na(+)-K(+)-ATPase in rat small intestine. 166 91

The effects of acute and chronic hyperglycemia on the kinase activity of insulin receptors in vivo were studied in the rat. Skeletal muscle-derived insulin receptors were isolated, with preservation of the in vivo phosphorylation state, from nondiabetic rats subjected to hyperinsulinemic clamps at either euglycemia (mean 5.2 mM) or hyperglycemia (14.4 mM) or from streptozocin-induced diabetic rats at euglycemia (5.1 mM) or hyperglycemia (14.2 mM). Kinase activity toward histone of insulin receptors from nondiabetic animals rendered hyperglycemic for 80-90 min was 50% higher than that of receptors from rats clamped at euglycemia (mean +/- SE 4.5 +/- 0.4 vs. 3.0 +/- 0.3 fmol of phosphate into histone, respectively, P less than 0.02), although kinase activity of receptors isolated from animals rendered diabetic for 10-14 days before hyperglycemic or euglycemic clamps showed no such effect. These results suggest that acute hyperglycemia may increase insulin-receptor kinase activity in vivo, possibly augmenting glucose disposal thereby, whereas the chronic hyperglycemia of diabetes mellitus results in metabolic derangements that nullify this effect.
Diabetes 1991 May
PMID:Regulation of rat insulin-receptor kinase by glucose in vivo. 167 63

Six high operative risk patients with urinary retention caused by benign prostatic hyperplasia were managed with an intraprostatic spiral at our hospital. Three of them had severe coronary artery disease, 1 had uremia, 1 had cerebral stroke and 1 had poorly controlled diabetes mellitus. The urinary retention was successfully relieved by the intraprostatic spiral in all patients. No operative mortality or severe complication was encountered. One patient experienced a repeat attack of urinary retention due to proximal migration of the spiral. Four patients complained of urgency, which was relieved by anticholinergic agents. Stone incrustation was found on 2 out of 3 spirals removed (66%), and the stone turned out to be calcium phosphate and struvite by scanning electron microscopy and infrared spectrophotometry. In 1 patient, stone formation was so abundant that it almost obstructed the lumen of the redundant tip of the spiral. From our preliminary results, the intraprostatic spiral seems to be a good alternative to an indwelling catheter for patients awaiting prostatectomy. Nevertheless, the potential complication of stone incrustation should be anticipated and it is suggested to remove the device as soon as possible or to replace it at regular intervals.
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PMID:Stone incrustation: a relevant complication of the intraprostatic spiral. 171 80


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