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)

We have recently reported that type II diabetic subjects with macroangiopathy have a higher activity of aldehyde dehydrogenase (ALDH) in blood than those without clinical vascular disease. ALDH activity was measured as the elimination of acetaldehyde added to a blood homogenate in vitro. We have re-examined our clinical material with another assay of ALDH which uses indole-3-acetaldehyde as substrate and measures the formation of indole-3-acetic acid. A negative correlation between the half-life of acetaldehyde and the formation of indole-3-acetic acid was found in the group of subjects free from vascular disease (r = -0.55, p less than 0.01). Thus, a rapid elimination of acetaldehyde corresponded to a rapid formation of indole-3-acetic acid. No such correlation was found in subjects with macroangiopathy. These results suggest that the 2 groups, with and without clinical vascular disease, have differences in isoenzyme composition, in the kinetic properties of the enzyme, or in the non-enzymatic binding of acetaldehyde.
Diabetes Res 1987 Oct
PMID:Aldehyde dehydrogenase activity and vascular disease in type II diabetes--a comparison between 2 different assays for activity. 342 70

A large-molecular-weight proinsulin-immunoreactive protein fraction was obtained from an extract of fetal bovine pancreases by gel filtration in 6 M guanidine-1 M acetic acid. Concanavalin A-Sepharose-affinity column chromatography of the large-molecular-weight fraction yielded a discrete alpha-methyl-mannoside-displaceable immunoreactive peak that also displayed N-acetylglucosamine-specific binding to wheat germ lectin-Sepharose. Chemically tritiated and radioiodinated lectin-reactive proteins interacted specifically with antibodies to insulin and bovine proinsulin. Immunochemically purified (reaction with antibodies followed by separation of antigen-antibody complexes on protein A-Sepharose) radiolabeled lectin-reactive proteins were analyzed by gel filtration in guanidine-acetic acid and by sodium dodecyl sulfate polyacrylamide gel electrophoresis after disulfide bond-cleavage treatments. Results from these studies suggest the existence of an approximately 67,000-Mr glycoprotein that contains antigenic domains common to proinsulin and insulin.
Diabetes 1987 Apr
PMID:Evidence for presence of proinsulin-immunoreactive glycoprotein(s) in fetal bovine pancreatic extracts. 354 49

The effects of castration on diabetes-induced increases in collagen cross-linking and vascular permeability and on polyol levels in new granulation tissue formed after induction of streptozocin (STZ) diabetes were examined in male Sprague-Dawley rats. New granulation tissue formation was induced by implanting sterile polyester fabric subcutaneously (s.c.) at the time of STZ injection 3 wk before assessment of vascular permeability and collagen cross-linking. Castration was performed 10 days before implanting the fabric. The characteristic increases in collagen cross-linking (manifested by decreased solubility in 0.5 M acetic acid) and in albumin permeation of the vasculature seen in intact diabetic rats were completely prevented by castration. Net collagen accumulation was not affected by diabetes or castration. Castration also markedly diminished diabetes-induced increases in tissue levels of sorbitol and completely prevented the decreases in tissue levels of myo-inositol and scyllo-inositol observed in intact diabetic rats, but had no effect on serum glucose levels, nonenzymatic glycosylation of plasma and granulation tissue proteins, or plasma somatomedin-C levels. The demonstration that castration prevents diabetes-induced increases in vascular permeability and collagen cross-linking as well as imbalances in tissue levels of sorbitol, myo-inositol, and scyllo-inositol in this model indicates that all of these changes are sex steroid-dependent phenomena. While the pathogenesis of these vascular permeability and collagen cross-linking changes is clearly multifactorial, these new findings: indicate that the role of sex steroids in the development of late complications of diabetes may be far more important than hitherto suspected, and suggest an explanation for the clinical observation that diabetic complications are uncommon in prepubertal diabetic subjects regardless of duration of diabetes.
Diabetes 1986 Jan
PMID:Sex steroid dependency of diabetes-induced changes in polyol metabolism, vascular permeability, and collagen cross-linking. 394 Sep 9

An orally active inhibitor of aldose reductase, 1,3-dioxo-1H-benz[de]-isoquinoline-2(3H)acetic acid (AY-22,284), prevented cataractous changes in cultured lenses exposed to high concentrations of galactose. When given orally, AY-22,284 markedly decreased the accumulation of polyols in the lenses and sciatic nerves of galactosemic rats and rats with streptozotocin-induced diabetes. In addition, treatment of galactosemic rats with AY-22,284 effectively suppressed the formation of cataracts.
 ...
PMID:Polyol accumulation in galactosemic and diabetic rats: control by an aldose reductase inhibitor. 427 Jul 94

1. In an attempt to define the importance of acetate as a metabolic precursor, the activities of acetyl-CoA synthetase (EC 6.2.1.1) and acetyl-CoA hydrolase (Ec 3.1.2.1) were assayed in tissues from rats and sheep. In addition, the concentrations of acetate in blood and liver were measured, as well as the rates of acetate production by tissue slices and mitochondrial fractions of these tissues. 2. Acetyl-CoA synthetase occurs at high activities in heart and kidney cortex of both species as well as in rat liver and the sheep masseter muscle. The enzyme is mostly in the cytosol fraction of liver, whereas it is associated with the mitochondrial fraction in heart tissue. Both mitochondrial and cytosol activities have a K(m) for acetate of 0.3mm. Acetyl-CoA synthetase activity in liver was not altered by changes in diet, age or alloxan-diabetes. 3. Acetyl-CoA hydrolase is widely distributed in rat and sheep tissues, the highest activity being found in liver. Essentially all of the activity in liver and heart is localized in the mitochondrial fraction. Hepatic acetyl-CoA hydrolase activity is increased by starvation in rats and sheep and during the suckling period in young rats. 4. The concentrations of acetate in blood are decreased by starvation and increased by alloxan-diabetes in both species. The uptake of acetate by the sheep hind limb is proportional to the arterial concentration of acetate, except in alloxan-treated animals, where uptake is impaired. 5. Acetate is produced by liver and heart slices and also by heart mitochondrial fractions that are incubated with either pyruvate or palmitoyl-(-)-carnitine. Liver mitochondrial fractions do not form acetate from either substrate but instead convert acetate into acetoacetate. 6. We propose that acetate in the blood of rats or starved sheep is derived from the hydrolysis of acetyl-CoA. Release of acetate from tissues would occur under conditions when the function of the tricarboxylic acid cycle is restricted, so that the circulating acetate serves to redistribute oxidizable substrate throughout the body. This function is analogous to that served by ketone bodies.
 ...
PMID:Production and utilization of acetate in mammals. 444 81

Somatostatin-like immunoreactivity (SRIF-LI) content in 2 N acetic acid extracts of hypothalamus, gastric antrum, and pancreas was measured in genetically obese (C57BL/6J ob/ob and db/db) and diabetic (C57BL/KsJ db/db and ob/ob) mice and normal littermate controls from 5 to 24 wk to determine the relationship of previously reported changes to the development of metabolic abnormalities. Hypothalamic SRIF-L concentration was similar in control, diabetic, and obese mice at all ages and increased progressively with age in all groups. Gastric antrum SRIF-LI was similar in all groups of mice at all ages. Obese mice gained weight progressively and showed moderate hyperglycemia and marked hyperinsulinemia from 5 wk of age. Pancreatic SRIF-LI content in obese (C57BL/6J) animals was similar to that in lean littermate controls, but pancreatic SRIF-LI concentration (expressed by weight or protein content) was decreased until 8 (6J ob/ob) and 10 (6J db/db) wk. Diabetic (C57BL/KsJ) mice showed a similar metabolic pattern until 10 wk with no change in pancreatic SRIF-LI content or concentration. Thereafter a progressive fall in serum insulin and a marked rise in serum glucose was associated with increasing pancreatic SRIF-LI content and concentration. These studies suggest that the genetically hyperphagic syndromes are unassociated with any change in hypothalamic or gastric SRIF-LI; that pancreatic SRIF-LI increases occur in response to, rather than as the cause of, relative hypoinsulinemia; and that the genetic background of the mice (KsJ or 6J) rather than the mutant gene (db or ob) determines the defect in carbohydrate metabolism and the pancreatic SRIF-LI response.
Diabetes 1980 Sep
PMID:Temporal relationship of tissue somatostatin-like immunoreactivity to metabolic changes in genetically obese and diabetic mice. 610 73

Immunoreactive somatostatin (IRS) was measured in extracted plasma obtained from the hepatic portal vein (PV) and inferior vena cava (IVC) of acute, untreated, spontaneously diabetic Wistar rats (BBL), insulin-treated diabetic rats, and nondiabetic controls. Acetic acid extracts of the pancreas and entire gastrointestinal tract were assayed for IRS, and the volume density of pancreatic D-, A-, and B-cells was determined by quantitative morphometry. The concentration of IRS in the PV and IVC of the untreated diabetic rats was significantly elevated compared with controls, with a much greater percent increase in the IVC compared with the PV. Insulin treatment for 4-6 wk restored the elevated PV and IVC levels to control values. The pancreatic content of IRS and the volume density of D-cells was severely reduced in the diabetic groups whereas gut IRS was unchanged. These data suggest that the elevated blood levels are secondary to insulin deficiency and result from altered peripheral metabolism and/or increased secretion of IRS most probably from the gut. The increased peripheral blood concentration of IRS raises the possibility of an endocrine role of circulating somatostatin in diabetes. The reduction in pancreatic IRS found in this model is probably secondary to insulitis and contrasts with the D-cell augmentation reported in streptozotocin-diabetic rats.
Diabetes 1980 Sep
PMID:Elevated portal and peripheral blood concentration of immunoreactive somatostatin in spontaneously diabetic (BBL) Wistar rats: suppression with insulin. 610 76

A rapid method for determining urinary indole-3-acetic acid (IAA) is introduced as the tumor-marker for the screening and diagnostic purpose of cancer patients by means of high performance liquid chromatography (HPLC). Its clinical significance is discussed along with a review of literatures. The IAA concentration and creatinine level of optionally collected urine samples were measured and used for the calculation of IAA amount per unit creatinine (microgram IAA/mg creatinine) in urine. Thus, an amount of 24-hours urinary IAA could be calculated without collecting a whole day's urine supply. Analysis of urinary IAA was performed within 10 minutes by HPLC. Urinary IAA level is usually high in the patients with the upper G-I tract cancers such as gastric cancer, esophageal cancer and hepato-biliary tract cancer, and also malignant hematopoietic disorders. But it is also high in non-cancer patients such as liver cirrhosis, diabetes mellitus and cholelithiasis occasionally. The patients with high urinary IAA level also showed high urinary levels of 5-hydroxy indoleacetic acid (5-HIAA) and monoamine oxidase activity (MAO). It was characteristic that hepatocellular carcinoma showed slight elevation of urinary IAA with normal levels of 5-HIAA and MAO. It is conclusive that the positive rate of elevated urinary IAA level was high in the patients with gastric cancer with ulcer-forming type in its morphological classification, and its level tends to elevate as the disease progresses. Therefore, the measurement of urinary IAA level in an optionally collected urine sample, as the tumor-marker, can be useful to check the progression and regression of gastric cancer.
 ...
PMID:[A rapid method for determining urinary indoleacetic acid concentration and its clinical significance as the tumor-marker in the diagnosis of malignant diseases]. 620 79

Uncontrolled diabetes in rats is associated with reduced levels of both serum somatomedins and hepatic somatomedins. Hepatic somatomedins are recognized after extraction with 5 mol/L acetic acid, have a higher molecular weight (about 30,000) than serum somatomedins (about 8,000), despite acid conditions that dissociate somatomedins from circulating carrier proteins, and stimulate cartilage when given in vivo. To determine if hepatic somatomedins--as potential prohormones--have insulin-like activity comparable with serum somatomedins, their effects on rat epididymal adipose tissue were examined. Somatomedins were prepared from serum and liver extracts by gel filtration on Sephadex G-75, pH 2.4. In initial studies with fat pad segments, extracted hepatic somatomedins increased glucose oxidation only 64 +/- 11% above buffer (mean +/- SEM), while stimulation of 372 +/- 48% was provided by extracted serum somatomedins of comparable cartilage-stimulating potency (P less than 0.01, liver v serum). Further examination was performed with isolated adipocytes in a system sensitive to insulin at a concentration of 10 microU/mL (stimulation 100% above buffer). In dose-response studies measuring glucose oxidation, hepatic somatomedins had insulin-like activity of 16 microU/mL versus 55 microU/mL for serum somatomedins equipotent on cartilage (P less than 0.05); measuring glucose incorporation into total lipids, hepatic somatomedins had undetectable activity while serum somatomedins had activity of 28 microU/mL. It is concluded that hepatic somatomedins with potent cartilage-stimulating activity have greatly reduced insulin-like activity. The apparent dissociation in biologic activity of hepatic somatomedins suggests that while they may be prohormones, they may also represent a class of growth factors separate from the circulating somatomedins.
 ...
PMID:Nutrition and somatomedin. X. Comparison of insulin-like activity of somatomedins extracted from liver and serum. 641 11

Children with insulin-dependent diabetes mellitus (IDDM) were examined for scleroderma-like changes of digital sclerosis and joint contractures. Of the 104 patients, 19 (18%) demonstrated these features; five patients had both multiple joint involvement and skin changes; three were studied in detail. All three had restrictive pulmonary disease. Histopathology of skin in these three patients demonstrated increased accumulation of collagen in the lower dermis. In two of the patients, the extractability of collagen in 0.5 N acetic acid was decreased by about 50% as compared with normal controls, which suggests increased cross-linkage of collagen. In addition, the mean nonenzymatic glycosylation of collagen in these three patients was 13 times that of controls. The results indicate that distinct histopathologic and biochemical changes can be detected in the skin of these patients. The results further support the hypothesis that nonenzymatic glycosylation may alter the turnover of collagen, thus contributing to the development of a scleroderma-like syndrome with skin, joint, and pulmonary findings in patients with IDDM.
Diabetes Care
PMID:Scleroderma-like changes in insulin-dependent diabetes mellitus: clinical and biochemical studies. 673 83


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