salicylates and Diabetes-Mellitus

Topics: Acidosis; Bicarbonates; Biguanides; Diabetes Mellitus; Epilepsy; Ethanol; Fructose; Heart Failure; Humans; Hypoglycemic Agents; Lactates; Leukocytosis; Methanol; Neoplasms; Physical Exertion; Salicylates; Shock

Topics: Administration, Oral; Clinical Trials as Topic; Diabetes Mellitus; Fatigue; Fatty Acids, Nonesterified; Glucose; Glucose Tolerance Test; Humans; Insulin; Salicylates

Salicylates are among the oldest medicinal compounds known to humans, and have been used to reduce fever, pain, and inflammation. The major oral salicylates are aspirin and salsalate, both of which are rapidly metabolized to salicylate in vivo. Owing to its acetyl group, aspirin irreversibly inhibits cyclo-oxygenases and thus blocks platelet aggregation, whereas salsalate has been used for treatment of inflammatory diseases such as rheumatoid arthritis. Recently, beneficial effects of salicylates in type 2 diabetes and cancer have been proposed. This has led to renewed interest in understanding how these simple molecules have such diverse and multifaceted effects. Here we discuss the idea that AMP-activated protein kinase (AMPK) might mediate some effects of salicylate-based drugs, particularly by modulating cellular metabolism.

Topics: AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Diabetes Mellitus; Enzyme Activation; Humans; Neoplasms; Salicylates

Naturally occurring regulatory T cells (Treg) driven by their transcriptional controller Foxp3 are compromised in immune-mediated disorders and confer protection when adoptively transferred. We examined the Ras-inhibitory effect on functional determinants of Treg in vivo and in vitro. Ras was inhibited in Jurkat T cells by transfection with a dominant-negative form of Ras, or by shRNA for N-Ras, K-Ras, and H-Ras, or by farnesylthiosalycylic acid, a small-molecule inhibitor. Except for H-Ras transduction with shRNA, each inhibitory mode increased expression of Foxp3 and nuclear factor of activated T cell proteins, and surface expression of CD25. Ras inhibition in PBMC and spleen-derived lymphocytes reproduced these findings. The heightened Foxp3 expression reflected both increased basal cellular protein and peripheral conversion of non-Treg to Treg. Ras inhibition enhanced Treg-induced suppression; thus, when adoptively transferred to mice, Ras-inhibited Treg reduced the incidence of diabetes. Inhibition of Foxp3 by respective siRNA reversed the enhancement. Thus, inhibition of the N- or K-Ras isoform triggers an anti-inflammatory effect by up-regulating, via Foxp3 elevation, the numbers and functional suppressive properties of Treg.

Topics: Adoptive Transfer; Animals; CD4-Positive T-Lymphocytes; Cell Differentiation; Cell Nucleus; Coculture Techniques; Diabetes Mellitus; Enzyme Inhibitors; Farnesol; Forkhead Transcription Factors; Humans; Interleukin-2 Receptor alpha Subunit; Jurkat Cells; Leukocytes, Mononuclear; Lymphocyte Activation; Mice; Mice, Inbred BALB C; NFATC Transcription Factors; Proto-Oncogene Proteins p21(ras); RNA Interference; Salicylates; Spleen; T-Lymphocytes; T-Lymphocytes, Regulatory; Transfection; Up-Regulation

Topics: Adjuvants, Pharmaceutic; Animals; Diabetes Mellitus; Humans; Insulin; Linoleic Acids; Rats; Salicylates; Suppositories; Surface-Active Agents

Topics: Albuminuria; Bromphenol Blue; Cellulose; Diabetes Mellitus; Diabetic Nephropathies; Evaluation Studies as Topic; Humans; Nephelometry and Turbidimetry; Reagent Strips; Salicylates; Salicylic Acid; Sensitivity and Specificity

Three side-room tests (latex bead immunoagglutination test, LBT; 25% sulphosalicylic acid test, SST; microalbutest, MAT) for the detection of microalbuminuria in diabetics are described and their screening potential and practicability assessed. One hundred insulin-dependent diabetics attending a diabetic clinic provided an early morning urine sample (Albustix-negative) which was subjected to each of the three tests, and urinary albumin concentration (UA) was assayed by RIA. Tests were assessed in random order by two trained operators using a semiquantitative grading scale with 100% concordance between 10 observers. All test results greater than or equal to trace +ve were sufficiently sensitive (sensitivity greater than or equal to 90%) in detecting UA greater than 15 mg/l, but MAT exhibited a significantly reduced specificity (69%) and positive predictive value (58%). For a reference UA greater than 30 mg/l, LBT and SST results greater than or equal to trace +ve and MAT results greater than or equal to +ve showed a sensitivity of 100%, a specificity greater than 85% and a positive predictive value greater than 60%. Reagent shelf-life was shortest with LBT. SST involved centrifugation or filtration. Technical skill required was highest with LBT and lowest with MAT. Costs were slightly higher with LBT than SST and were not available for MAT.

Topics: Albuminuria; Benzenesulfonates; Colorimetry; Diabetes Mellitus; Humans; Indicators and Reagents; Microchemistry; Salicylates

The dermal microvasculature has been compared in 51 diabetics and 51 matched non-diabetic controls using tissue measurement techniques and functional assessments of blood vessel reactivity. Blood vessel walls were thicker in different groups of diabetics than the controls (p less than 0.01) but the degree of thickness did not differ between patients with insulin-dependent diabetes mellitus and those with non-insulin-dependent diabetes mellitus or between diabetics with and without vascular complications. Vascular lumina were narrower in diabetics than in controls (p less than 0.01) and diabetics with vascular complications had a greater reduction in luminal area than those without such complications (p less than 0.001) but the luminal area did not differ between the insulin-dependent and the non-insulin-dependent groups. The luminal perimeter was also reduced in the diabetic group compared to controls. The weal and flare response to intracutaneous histamine acid phosphate (50 micrograms) was markedly decreased (p less than 0.001) in diabetic subjects compared with controls, as was the response to a topically applied vasodilator (Transvasin). The degree of reduction did not differ between patients with insulin-dependent diabetes mellitus and those with the non-insulin-dependent disease but diabetics with vascular complications show impaired responses as compared to those without. The maximum increase in skin temperature on the volar surface of the right middle finger during a period of reactive hyperaemia following 3 min of cuff-induced ischaemia was also markedly decreased in diabetics compared with control subjects. It did not differ between those with insulin-dependent diabetes mellitus and those with the non-insulin-dependent disease but did between diabetics with vascular complications as compared with those without. This study confirms that the cutaneous vasculature of diabetics differs markedly from that of matched control subjects. The results also indicate that there are significant differences between diabetics with vascular complications and those without. The quantitative approaches adopted may have predictive value.

Topics: Adult; Aged; Benzocaine; Biometry; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Drug Combinations; Histamine; Humans; Hyperemia; Middle Aged; Niacin; Salicylates; Skin; Skin Temperature

Diabur-test 5000, a new test strip for estimation of urinary glucose, was compared with the hexokinase glucose-6-phosphate dehydrogenase method in more than 2500 urine samples. By combination of two test ranges glucose concentrations of up to 5% can be detected by the strip test. After a reading time of 2 minutes, very precise estimation of urinary glucose is possible in eight steps from negative to 5%. False estimations of more than one color step virtually do not occur. Ketone bodies, salicylic acid and several antibiotics do not influence the test strip. Ascorbic acid shows a slight influence only in concentrations above 40 mg/dl. This influence disappears with glucose concentrations of more than 0.5%. Good correlation with the reference method, wide range of readings and simple handling make the test strip suited for the laboratory and particularly for self control of diabetic patients.

Topics: Anti-Bacterial Agents; Ascorbic Acid; Diabetes Mellitus; Glycosuria; Humans; Indicators and Reagents; Ketone Bodies; Reagent Strips; Salicylates

Topics: Arginine; Cyclooxygenase Inhibitors; Diabetes Mellitus; Glucose; Humans; Insulin; Insulin Secretion; Isoproterenol; Prostaglandins E; Salicylates; Secretory Rate

Topics: Animals; Diabetes Mellitus; Glucose; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Prostaglandins; Prostaglandins E; Salicylates

Topics: Blood Glucose; Diabetes Mellitus; Epinephrine; Humans; Insulin; Prostaglandins E; Salicylates

Adult-onset diabetics have markedly diminished or absent acute insulin responses to glucose that can be partially restored by sodium salicylate infusion. To determine whether this restoration of the acute insulin response is glucose dose dependent and whether complete restoration can be achieved, adult-onset diabetics with a mean fasting plasma glucose value of 216 +/- 20 mg. per deciliter (x +/- S.E.) were stimulated with various doses of intravenous glucose. Restoration occurred in a glucose dose-dependent manner. Complete restoration could not be achieved with the maximal tolerable glucose dose (80 gm.). Second phase insulin secretion also improved in a glucose dose-dependent manner. These findings are compatible with the hypothesis that defective insulin secretion in adult-onset, hyperglycemic diabetics is not due to absolute deficiency of insulin but may be a result of defective recognition of glucose signals by pancreatic B-cells--a defect that can be partially reversed by sodium salicylate.

Topics: Adult; Aged; Diabetes Mellitus; Dose-Response Relationship, Drug; Glucose; Humans; Insulin; Kinetics; Middle Aged; Salicylates

Topics: Adult; Arginine; Blood Glucose; Diabetes Mellitus; Glucose; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Prostaglandins E; Salicylates

Topics: Blood Glucose; Diabetes Mellitus; Drug Synergism; Glyburide; Humans; Insulin; Salicylates

Topics: Animals; Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Carotid Arteries; Catheterization; Cyclopentanes; Diabetes Mellitus; Dogs; Drug Evaluation, Preclinical; Femoral Artery; Glass; Guinea Pigs; In Vitro Techniques; Methods; Platelet Adhesiveness; Propionates; Pyrroles; Rabbits; Rats; Salicylates; Species Specificity; Sulfonylurea Compounds; Time Factors; Veins

Topics: Blood Glucose; Diabetes Mellitus; Humans; Salicylates

Topics: Administration, Oral; Age Factors; Blood Glucose; Blood Specimen Collection; Body Height; Body Weight; Contraceptives, Oral; Diabetes Mellitus; Diagnostic Errors; Diuretics; Drug-Related Side Effects and Adverse Reactions; Follow-Up Studies; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Salicylates; Sex Factors; Steroids

Topics: Acetone; Biguanides; Diabetes Complications; Diabetes Mellitus; Diabetic Ketoacidosis; Diet Therapy; Glucose Tolerance Test; Glycosuria; Holidays; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Interpersonal Relations; Prediabetic State; Salicylates; Sports; Travel

Topics: Arginine; Blood Glucose; Circadian Rhythm; Diabetes Mellitus; Dietary Fats; Dietary Proteins; Fasting; Fatty Acids, Nonesterified; Glucose; Growth Hormone; Heparin; Humans; Hypopituitarism; Insulin; Nicotinic Acids; Obesity; Salicylates; Sleep; Time Factors

Topics: Adolescent; Adult; Aspirin; Complement System Proteins; Diabetes Mellitus; Diabetic Retinopathy; Female; Humans; Male; Middle Aged; Salicylates

Topics: Amylases; Blood Chemical Analysis; Chromatography; Clinical Enzyme Tests; Colorimetry; Diabetes Mellitus; Electrophoresis; gamma-Globulins; Glucose; Humans; Intestinal Obstruction; Liver Cirrhosis; Maltose; Pancreatitis; Salicylates; Starch

Topics: Acidosis; Acute Kidney Injury; Alcoholism; Anuria; Child; Diabetes Mellitus; Dialysis; Humans; Hypertension; Hypertension, Malignant; Hyponatremia; Malaria; Peritoneal Dialysis; Poisoning; Renal Dialysis; Renal Insufficiency; Salicylates; Uremia

Topics: Blood; Diabetes Mellitus; Female; Humans; Insulin; Male; Phenformin; Pyruvates; Salicylates; Sulfonamides

Topics: Diabetes Mellitus; Humans; Israel; Salicylates

Topics: Blood Glucose; Diabetes Mellitus; Fatty Acids; Fatty Acids, Nonesterified; Humans; Plasma; Salicylates; Sodium Salicylate

Topics: Diabetes Mellitus; Salicylates

Topics: Diabetes Mellitus; Fatty Acids; Humans; Salicylates

Topics: Aspirin; Diabetes Mellitus; Humans; Insulin; Salicylates

Topics: Aspirin; Diabetes Mellitus; Dinitrophenols; Humans; Nitrophenols; Salicylates

Topics: Blood Glucose; Diabetes Mellitus; Epoxy Compounds; Humans; Male; Propanols; Salicylates; Sodium Salicylate

Topics: Diabetes Mellitus; Humans; Liver; Liver Function Tests; Salicylates