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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The principles of teratology are described, and animal models for research in abnormal ocular development and clinical studies of human teratogens are surveyed. A review is made of presumed ocular teratogenic agents: radiation; external environmental teratogens; maternal conditions such as infections, diabetes, and epilepsy; alcohol and drugs such as thalidomide, retinoic acid, and coumarin anticoagulants; and other agents, such as cigarettes.
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PMID:Ocular teratology. 188 22

In the present study, we have determined the specific glucocorticoid receptors in cultured human skin fibroblasts with [3H]dexamethasone as the ligand. The whole-cell assay was employed for determination of glucocorticoid receptor densities and binding affinities in fibroblast cultures established either from 16 healthy control subjects, from 4 patients with active progressive systemic sclerosis (PSS), from 3 patients with keloids and 3 patients with diabetes mellitus. The receptor densities in PSS, keloid, diabetes and control fibroblasts were in the same range, the values being 6.3 +/- 4.9, 7.7 +/- 3.6, 5.3 +/- 1.3 and 7.9 +/- 6.2 fmol/micrograms DNA (mean +/- SD), respectively. In further studies, the cells were incubated with 10(-7) M dexamethasone for 4 or 9 days before the receptors were assayed. The specific binding of [3H]dexamethasone in steroid treated cultures was 62 and 13% of that observed in controls, suggesting down-regulation. In contrast, incubation of fibroblasts with 10(-5) M all-trans-retinoic acid did not alter the binding of [3H]dexamethasone, suggesting lack of pharmacologic interference at the receptor level.
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PMID:Glucocorticoid receptors in cultured human skin fibroblasts: evidence for down-regulation of receptor by glucocorticoid hormone. 245 69

Vitamin A (retinol) is required for insulin secretion, and retinoic acid substitutes for retinol in this function. To determine if retinol acts at the beta-cell level, we assayed beta-cells of the rat insulinoma (RINm5F) line for cytosolic retinol- and retinoic acid-binding proteins (CRBP and CRABP) by radioimmunoassay (RIA) and [3H]retinol and [3H]retinoic acid binding to cytosol extracts. Furthermore, we tested whether insulin release from cells was affected by addition of retinol or retinoic acid to culture medium. RINm5F cells were grown to near confluence before assay of CRBP and CRABP. Scatchard analysis showed the Kd for retinol to be approximately 6 nM at a level of 4.5 pmol/mg protein or 300,000 sites/cell. Sucrose density-gradient assay showed single discrete peaks migrating at 2S for both retinol and retinoic acid. RIA of whole-cell extracts showed CRBP and CRABP levels of 5.27 +/- 0.41 and 2.95 +/- 0.75 pmol/mg protein, respectively. Retinol (1.75 microM) and retinoic acid (0.175 and 1.75 microM) increased KCl-induced insulin release. Considered together, the presence of CRBP and CRABP in a beta-cell line and the increase in KCl-induced insulin release by retinol and retinoic acid are consistent with the idea that retinol has a functional role in insulin secretion and suggest a potential mechanism of action at the beta-cell level similar to that observed in other retinoid-responsive cells.
Diabetes 1989 Dec
PMID:Cytoplasmic retinoid-binding proteins and retinoid effects on insulin release in RINm5F beta-cells. 255 41

The continuously growing, insulin-secreting cell line RINm5F does not respond to glucose with increased rates of insulin secretion and cell proliferation. The possibility that retinoic acid, which acts as a differentiating agent in several cell systems, could induce such responses to glucose has been investigated. Retinoic acid (10(-6)-10(-5) mol/l) failed to affect the cell viability, cell proliferation, 3H-thymidine incorporation or the DNA contents of the cultured RINm5F cells, irrespective of the glucose concentration of the culture medium. The insulin release was not affected either by glucose or by retinoic acid. Higher concentrations of the drug (10(-4) mol/l) proved toxic to the cells. The incorporation of 3H-mannose and 3H-glucosamine into TCA precipitable material of the RINm5F cells was strongly decreased by an increased glucose concentration of the medium. The incorporation of 3H-mannose, but not that of 3H-glucosamine, into macromolecules which could be precipitated with Concanavalin A or wheat germ lectin was diminished by retinoic acid (10(-5) mol/l).
Diabetes Res 1986 May
PMID:Effects of retinoic acid on growth, insulin secretion, and hexose incorporation into macromolecules of a continuously growing, insulin-secreting cell line (RINm5F). 352 18

The adhesion of blood cells to endothelium can be studied in vitro using human endothelial cells in culture. This experimental model and radiometric techniques provide us with a simple system to quantify the adhesion of blood cells to endothelium. Normal human granulocytes isolated by density gradient adhere to normal endothelial cells in a proportion of 25%. Human promyelocytic cells (HL 60) induced by retinoic acid into mature cells adhere as well as normal granulocytes while the noninduced adhere poorly to endothelium. A small percentage of normal red cells attach to endothelial cells while red cells from patients with sickle cell anemia or diabetes mellitus have a significantly increased adhesion to endothelial cells (P greater than 0.001). This adhesion is statistically correlated with the extent and severity of vascular complications in diabetes mellitus (P less than 0.05). The addition of fibrinogen significantly increased (P less than 0.01) the adhesion of normal red cells, red cells from patients with sickle cell anemia or diabetes mellitus while gamma-globulins did not modify adhesion. Fibronectin potentiated the adhesion of normal red cells.
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PMID:Factors involved in cell adhesion to vascular endothelium. 619 16

Alterations in lipid metabolism have been reported under treatment of various skin disorders with oral retinoids. In 36 patients, mostly psoriatics, under administration of aromatic retinoid (Ro 10-9359) in various dosages serum triglycerides and cholesterol were estimated; in 25 out of 36 patients lipid analysis of the lipoproteins and apoproteins A (HDL) and B (LDL) has been performed. To reveal possible similarities of lipid changes under the two main retinoids we determined the same parameter in 10 patients with conglobate acne treated orally with 13-cis-retinoic acid (isotretinoin/Ro 4-3780 1mg/kg b.w.). Under both drugs serum triglyceride and cholesterol levels were significantly increased. In contrast to the results under the aromatic derivate the HDL- and LDL-cholesterol fractions were changed under isotretinoin. The apoprotein A (HDL) was found significantly increased under aromatic retinoid. Elevated serum lipids mostly occurred in patients having risk factors such as preexisting lipid abnormalities, obesity, diabetes mellitus, heavy smoking, alcohol abuse and hyperlipemia-inducing drugs. Patients to be treated with these drugs should be carefully followed up in order to minimize the risk for atheromatosis.
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PMID:[Changes in serum lipid fractions as a side effect of oral retinoids]. 621 75

We studied the effects of retinoids on islet cell-to-cell adhesiveness and glucose-induced insulin release from rat islets. For adhesion studies, islets were dispersed using low concentrations of trypsin. Thirteen cis-retinoic acid (13 cis-RA) was added to a suspension of 15 X 10(5) islet cells and adhesion of cells was quantitated using a hemocytometer. For functional studies, we measured biphasic insulin release from collagenase-isolated perifused islets, dispersed cells, and single large aggregates (clumps) of islet cells. Thirteen cis-RA (10(-4) M) stimulated insulin secretion at 9.7, 12.5, 16.7, and 27.7 mM glucose. Maximal effects of 13 cis-RA (174% of control) were evident during second phase release at 9.7 mM glucose. Thirteen cis-RA (10(-7) and 10(-6) M) caused cells to adhere to each other, and at higher concentrations, 13 cis-RA caused dispersed cells to reaggregate into a single clump. These retinoid-induced clumps were perifused in a Bio-Gel P-2 gel column. Secretion from the clump was twofold greater than from an equal number of perifused dispersed cells. Electron microscopic and freeze-fracture examination of the clump showed reaggregated cells to be intact and the presence of gap junctions between cells. In conclusion, 13 cis-RA has marked effects on islet cell-to-cell adhesiveness. Trypsin-dispersed cells reaggregated by 13 cis-RA have anatomical contacts and secrete more insulin as an aggregate than as dispersed cells. Thirteen cis-RA increases insulin release possibly by increasing adhesion or interactions between beta-cells.
Diabetes 1983 Jun
PMID:Cellular mechanisms of insulin release. Effects of retinoids on rat islet cell-to-cell adhesion, reaggregation, and insulin release. 635 84

Many species of monocellular eukaryots as well as the majority of animal cell and plant tissues show the presence of peroxisomes or microperoxisomes. Their size, shape and internal organization may differ in various cellular types significantly. Typical components of animal cell peroxisomes are the membrane, matrix, low density compartment enriched in lipids, and the compartment containing D-amino acid oxidase. The group of four enzymes (catalase, D-amino acid oxidase, L-alpha-OH-acid oxidase) the location of which had been originally discovered in peroxisomes of hepatocytes of rodents was later widened by approximately forty further enzymes. It is though probable that evolution brought along a reduction and loss of various metabolic functions of peroxisomes and a decrease in the number of enzymes. Peroxisomes are characterized by high variability of the enzymatic content in dependence on the nutritional conditions and the effect of xenobiotics. Fasting, diabetes mellitus, high-lipid diet, peroxisome proliferators induce several peroxisomal enzymes, especially fatty acids beta-oxidation. The mechanism of the impact of heterogeneous substances on the gene transcription has been clarified recently. Substances as fibrates, retinoic acid, polyunsaturated fatty acids activate specific types of receptors-PPAR (peroxisome proliferators activated receptors) belonging to the superfamily of receptors activated by steroid hormones, thyroid hormones, and D-vitamins. A simultaneous induction of several peroxisomal enzymes can be achieved by the linkage between PPAR and specific areas of promotors of particular genes. Such areas-PPREs (peroxisomal proliferator response elements) with five repeated TGA(A/C/T)CT hexanucleotide sequences separated by one nucleotide were discovered in several peroxisomal genes. It is assumed that the stimulation of transcription can be achieved by the linkage between homodimers, and heterodimers of nuclear receptors on these DNA sections. The majority of peroxisomal proteins is synthesised in the cytoplasm, namely on polysomes being in matured forms. Unimpaired biogenesis of peroxisomes requires membrane transport proteins and presence of signal in polypeptide chain of imported proteins (PTS-peroxisomal targeting signal). The function of PTS in many peroxisomal proteins is fulfilled by the C-terminal tripeptide which is composed of amino acids, namely serine, lysine, and leucine (SKL-tripeptide), respectively by a tripeptide with a very similar composition in amino acids. Aside from this signal, still another signal exists, which is located at the N-end of peroxisomal proteins. The role of membrane proteins 70, 35, 256, 22, 15 kDa, is being discussed in relationship to the functions and diseases caused by impaired biogenesis of peroxisomes. (Fig. 4, Ref. 128.)
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PMID:Properties and biogenesis of peroxisomes. 773 95

Retinol and retinyl palmitate in the moderate doses tested in chemoprevention trials produce only a negligible increase in serum triglyceride levels. The effect is nonprogressive and is not associated with the kind of exaggerated response reported for interacting factors such as presence of diabetes mellitus and/or high baseline values for serum triglyceride concentration. These findings seem to represent an advantage for safety of retinol in relation to isotretinoin (13-cis-retinoic acid).
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PMID:Long-term vitamin A does not produce clinically significant hypertriglyceridemia: results from CARET, the beta-carotene and retinol efficacy trial. 788 45

Metabolic disorders including diabetes mellitus, glucose intolerance, dyslipidemias, hyperuricemia, and hypervitaminosis A have often been mentioned in association with diffuse idiopathic skeletal hyperostosis (DISH). Production of bone under the influence of insulin or retinol has been suggested as a possible mechanism for this disease. We prospectively studied metabolic disorders in 25 patients with DISH and 25 controls matched for age, sex, and body mass index. Correlations between simultaneously evaluated parameters were looked for. Obesity was prevalent in both groups. Serum levels of glucose, insulin, glycated hemoglobin, total cholesterol, HDL cholesterol, triglycerides, uric acid, retinol, and retinol binding protein were similar in the two groups. A positive correlation was found between body mass index and serum insulin. We found no correlation between serum levels of insulin and retinol. None of the metabolic parameters studied showed alterations likely to explain the development of hyperostosis. Other growth factors such as retinoic acid or insulin-like growth factor 1, perhaps produced on a paracrine basis, may be the cause of increased bone at enthesis production.
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PMID:[Forestier disease and metabolism disorders. A prospective controlled study of 25 cases]. 816 24


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