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 activity of the succinate dehydrogenase-coenzyme Q10 reductase from 120 diabetic patients was significantly lower (P less than 0.001) and the per cent deficiency was significantly higher (P less than 0.001) than that of the controls. The diabetes of 37 patients was controlled by diet; the enzyme activity was lower (P less than 0.001) and the deficiency was higher (P less than 0.02) than for controls. In decreasing effectiveness, Dymelor, Glyburide, Phenformin and Tolazamide inhibited the COQ10-enzyme, NADH-oxidase. Tolbutamide, Glypizide, and Chlorpropamide were noninhibitory to succinoxidase and NADH-oxidase. Patients receiving Tolazamide and Phenformin showed a higher incidence (P less than 0.001 to P less than 0.05) of COQ10-deficiency than patients controlled by diet or normal controls. Certain diabetic patients controlled by diet may have a deficiency of COQ10 which may be enhanced by the inhibition by certain commonly used antidiabetic drugs of COQ10-enzymes. A deficiency of COQ10 in the pancreas could impair bioenergetics, the generation of ATP, and the biosynthesis of insulin.
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PMID:Bioenergetics in clinical medicine. XI. Studies on coenzyme Q and diabetes mellitus. 107 May 15

To determine whether therapy with exogenous insulin or sulfonylureas results in a postprandial pattern of carbohydrate metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM) that resembles that in nondiabetic individuals, we employed a dual-isotope technique combined with forearm catheterization to examine meal disposition in NIDDM patients, before and after 3 mo of therapy with tolazamide and after 3 mo of therapy with exogenous insulin, with a randomized crossover design. Results were compared with those observed in nondiabetic subjects. Although both forms of therapy improved chronic glycemic control (glycosylated hemoglobin concentration went from 9.6 +/- 0.7 to 7.6 +/- 0.5 and 7.1 +/- 0.2%, respectively, P less than .01), exogenous insulin resulted in a lower postprandial glycemic response than tolazamide (P less than .001). Both agents comparably increased (P less than .01) fasting and integrated postprandial insulin concentrations. However, the initial rate of postprandial increase was greater with exogenous insulin (P less than .05). Tolazamide (P less than .05) but not exogenous insulin increased postprandial C-peptide concentrations. However, tolazamide did not improve the deficient early insulin release. Both agents (P less than .05) lowered postabsorptive hepatic glucose release (from 2.8 +/- 0.3 to 2.3 +/- 0.2 mg . kg-1 . min-1), but not to normal rates (1.8 +/- 0.1 mg . kg-1 . min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1987 Oct
PMID:Effects of tolazamide and exogenous insulin on pattern of postprandial carbohydrate metabolism in patients with non-insulin-dependent diabetes mellitus. Results of randomized crossover trial. 330 84

Using a double-blind crossover design, we studied the effect of tolazamide, an orally administered sulfonylurea, in 11 patients with non-insulin-dependent diabetes mellitus, poorly controlled on 40 units/day or more of insulin; all had previously failed to respond adequately to oral hypoglycemic agents and diet. In addition, six nondiabetic sex-, age-, and weight-matched controls were studied. Tolazamide significantly lowered fasting plasma glucose level from 272 +/- 21 to 222 +/- 31 mg/dL, increased fasting C peptide concentration from 0.09 +/- 0.03 to 0.28 +/- 0.10 pmole/mL (controls, 0.23 +/- 0.2 pmole/mL), and increased integrated C peptide concentration during a test meal (area under the curve) from 42 +/- 18 to 95 +/- 22 pmole/mL X min (controls, 94 +/- 8 pmole/mL X min). These data show that addition of tolazamide markedly increased fasting and meal-stimulated insulin secretion and modestly lowered fasting plasma glucose concentrations. We conclude that some patients who cannot achieve satisfactory control with oral hypoglycemic agents and diet may benefit from combined therapy with oral sulfonylurea agents plus insulin.
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PMID:Insulin and a sulfonylurea agent in non-insulin-dependent diabetes mellitus. 351 96

A unique hepatic adenoma developed in a 26-year-old woman who had used oral contraceptives for 10 years and Tolinase (tolazamide sulfonylurea) for adult-onset diabetes mellitus for five years. Clinically, radiographically, and grossly, the neoplasm showed the usual features of a hepatic adenoma, but microscopically it strongly resembled alcoholic hepatitis with steatonecrosis and Mallory bodies. The surrounding hepatic parenchyma was entirely normal. On transmission electron microscopy these Mallory bodies appeared to be tangles of intermediate filaments. They stained readily with antibodies to cytokeratin but not with antibodies to epidermal keratin or vimentin, just as in "alcoholic" hyalin.
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PMID:"Alcoholic hepatitis" in a hepatic adenoma. 359 92

Polypeptide hormones such as insulin must cross the vascular barrier to mediate their biologic actions. A substantial vascular barrier may be encountered in muscle and fat tissues, which are supplied by continuous capillaries lined with tightly joined endothelial cells. Endothelial cells have previously been shown to bind and release insulin with minimal degradation. Because 125I-labeled insulin transport was demonstrated to be receptor-mediated, factors regulating insulin-receptor binding may also affect the insulin transport rate across the vascular barrier. Since sulfonylureas may have a glucose-lowering action by altering insulin receptors, the effects of tolazamide and glyburide on vascular endothelial cell insulin receptors were evaluated. Exposure of aortic endothelial cells in culture to insulin at 37 degrees C resulted in a 75 percent loss of receptors. Five to seven days of tolazamide exposure led to a 35 percent time-dependent increase in insulin binding. More strikingly, tolazamide altered the dose-receptor to insulin-induced down-regulation. Cells down-regulated with insulin (10 ng/ml) showed a 100 percent increase in binding in the presence of tolazamide; a dose-dependent effect occurred at the 75 to 200 micrograms/ml dosage level. Scatchard analysis indicated that the increase in 125I-labeled insulin binding was due to an increase in receptor number. When insulin receptors were identified with 125I-labeled insulin, tolazamide-treated cells clearly showed an increase of a band at Mr = 145 K, the alpha subunit of the receptor. Tolazamide may thus help normalize glucose in diabetes by preventing receptor down-regulation in endothelial cells.
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PMID:Processing and transport of insulin by vascular endothelial cells. Effects of sulfonylureas on insulin receptors. 390 45

Although sulfonylureas have been used extensively in the treatment of non-insulin-dependent (type II) diabetes, controversy exists as to whether these agents act primarily by increasing insulin secretion or by enhancing insulin action. To determine whether sulfonylureas potentiate insulin action in the liver, we evaluated the ability of the sulfonylurea tolazamide to affect insulin-sensitive lipogenesis utilizing primary cultures of hepatocytes prepared from both normal and nonketotic streptozotocin-diabetic rats. Hepatocytes were cultured for 16 h in serum-free media with no additions, tolazamide alone (0.3 mg/ml), or insulin (10(-10) to 10(-7)M) in the absence and presence of tolazamide. Following culture, lipogenesis and specific insulin binding were assessed. Dose-dependent increases in lipogenesis were found in hepatocytes from both normal and diabetic rats after the chronic exposure to insulin. In hepatocytes from diabetic rats, the basal and the maximal insulin-stimulated rates of lipogenesis were only 27% and 13% of normal, respectively, establishing this as a model of hepatic insulin resistance. In the presence of tolazamide, significant potentiation of insulin action was found in hepatocytes from normal and diabetic rats although hepatocytes from diabetic animals remained relatively resistant to insulin when compared with those from nondiabetic animals. While exposure to tolazamide increased insulin responsiveness in both groups of cells, no changes in insulin sensitivity (ED50) were observed. Tolazamide significantly increased insulin binding (12%) in hepatocytes from normal rats cultured in the absence of insulin, but no alterations in insulin binding were found under incubation conditions in which tolazamide potentiated insulin action. These results give the first direct evidence for an insulin-dependent action of a sulfonylurea on the liver from both normal and diabetic rats and indicate that the enhancement of insulin responsiveness occurs through postbinding mechanisms.
Diabetes 1983 Mar
PMID:Potentiation of insulin action by a sulfonylurea in primary cultures of hepatocytes from normal and diabetic rats. 633 99

Tolazamide, a new oral hypoglycemic agent, was compared with tolbutamide, a related chemical compound, for stability of control of 12 patients suffering from maturity-onset diabetes mellitus. A short 12-week study was conducted which incorporated a cross-over design and the results were examined by variance analysis after dosage was individualized to the patient's requirements. Greater stability of fasting blood sugar was found on tolazamide; patients also had less glycosuria and lower fasting blood sugar on tolazamide. Tolazamide appeared to be between five and six times as potent as tolbutamide, mg. for mg.No hepatic, renal, hematologic or symptomatic toxic reactions were observed during the total of 72 person-weeks of tolazamide therapy.
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PMID:CLINICAL STUDIES OF TOLAZAMIDE AND TOLBUTAMIDE: COMPARATIVE EFFECTIVENESS OF CONTROL OF DIABETES MELLITUS. 1407 15