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

The transglutaminase involvement in phytohaemagglutinin (PHA) stimulated lymphocyte transformation (measured as (3H)thymidine incorporation) was studied in lymphocytes from 20 patients with type 2 diabetes mellitus and 20 healthy controls by including in the system the specific transglutaminase pseudosubstrate monodansylthiacadaverine (MDTC). In the presence of MDTC, (3H)thymidine incorporation was significantly and concentration-dependently reduced in both groups but more pronouncedly in the diabetes patients. The MDTC concentration needed to give a 50% reduction of the PHA-stimulated (3H)thymidine incorporation was significantly lower in lymphocytes from diabetic patients than in those from controls (p less than 0.02). The data suggest impaired lymphocyte transglutaminase function in type 2 diabetes mellitus.
Diabetes Res 1989 Apr
PMID:Transglutaminase-dependent lymphocyte transformation in type 2 diabetes mellitus. 257 78

Transglutaminase activity in rat islet homogenates was increased after preincubation of the islets at high glucose concentration, and severely decreased after preincubation in the presence of either 1,2-bis(2-chloroethyl)-1-nitrosurea or 2-cyclohexene-1-one. The stimulatory action of glucose was still observed when the islets were preincubated in the absence or extracellular Ca2+. The enzymic activity was decreased by NAD+ or NADP+ but not NADH or NADPH, and inhibited by GSSG more than by GSH. These findings suggest that the glucose-induced activation of transglutaminase may be related to induction of a more reduced redox state with subsequent change in thiol-disulfide balance.
Diabetes Res 1986 Mar
PMID:Glucose-induced activation of transglutaminase in pancreatic islets. 287 59

A method for capping of beta 2-microglobulin involving the transglutaminase inhibitor monodansylthiacadaverine was applied to lymphocytes from 17 patients with Type 2 diabetes mellitus and from a matched control group of 16 normoglycaemic healthy subjects. Monodansylthiacadaverine strongly inhibited the capping, which points to the involvement of transglutaminase in the redistribution of beta 2-microglobulin on the cell surface. The inhibition was more pronounced in lymphocytes from diabetic patients, indicating impaired transglutaminase function in Type 2 diabetes mellitus.
Diabetes Res 1987 May
PMID:Lymphocyte transglutaminase function may be impaired in type 2 diabetes mellitus. 288 30

We have examined the effect of glipizide, a hypoglycemic sulfonylurea, upon transglutaminase activity in human red blood cells. In a first series of experiments the in vitro effect of the drug was assessed. The results obtained showed that glipizide inhibits transglutaminase activity in human red blood cells. In a second approach, glipizide was administered orally to six type 2 diabetic patients during 3 months, in order to evaluate the long-term effect upon transglutaminase activity. Again, glipizide induced a significant decrease in the enzyme activity in blood red cells (P less than 0.01). We suggest that treatment of type 2 diabetes mellitus with hypoglycemic sulfonylureas could improve insulin effects by inhibiting cellular transglutaminase activity.
Diabetes Res Clin Pract 1988 May 19
PMID:The effect of hypoglycemic sulfonylureas on human red blood cell transglutaminase activity. 290 Jan 25

It has been suggested that cellular transglutaminases may play an important role in the process of receptor-mediated endocytosis. We have examined this premise by investigating the receptor-mediated endocytosis of two proteins, epidermal growth factor and alpha 2 macroglobulin in cells that are deficient in transglutaminases. We find that endocytic activity is normal in these cells, ruling out an obligatory role for transglutaminases in endocytosis. We do find, however, that dansylcadaverine is not an inhibitor of endocytosis in cells that lack transglutaminase activity. Immunofluorescent localization of dansylcadaverine in dansylcadaverine-treated cells demonstrates incorporation of the amino into endocytic vesicles. We believe that covalent coupling of dansylcadaverine to cellular membranes may account for its ability to interfere with endocytosis in certain susceptible cells.
Diabetes Care
PMID:Studies on the effects of dansylcadaverine and related compounds on receptor-mediated endocytosis in cultured cells. 614 51

The effect of diabetes on some enzymes of polyamine metabolism was studied in male rats 1-12 days after administration of streptozotocin. Hepatic ornithine decarboxylase activity decreased in the first days after the administration, but increased thereafter. The decrease was not due to an alteration of the ODC-antizyme concentration, nor to a posttranslational modification catalyzed by transglutaminase. S-adenosylmethionine decarboxylase and ornithine transaminase were both increased. Spermidine acetyltransferase activity was practically unchanged, while its inactivating factor was markedly decreased.
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PMID:Activity of some enzymes involved in the metabolism of polyamines in the liver of streptozotocin-diabetic rats. 615 27

We have examined the nonpancreatic actions of sulfonylureas on multiple aspects of insulin responsiveness in two target tissues for insulin, liver and fat. In vivo administration of tolazamide and glipizide reduced significantly the postabsorptive serum glucose levels in rats without altering the levels of insulin. This was consistent with extrapancreatic sites of drug action. The number and affinity of hepatic insulin receptors was not different from those of control rats. Using a tissue culture system for rat adipose tissue, a 20-h treatment with sulfonylureas markedly potentiated insulin action in fat cells. The primary augmentation was at the level of insulin-stimulated glucose transport. Again, there was no alteration of the insulin receptors located on the adipose tissue. Furthermore, consistent with the lack of an influence on insulin-induced receptor loss after in vitro treatment with sulfonylureas, the in vivo administration of these agents did not alter the transglutaminase activity in rat hepatic tissue. The data demonstrate that sulfonylureas potentiate the responsiveness of the target tissues for insulin. Thus, these hypoglycemic agents probably act by correcting some of the cellular lesions associated with the insulin resistance in type II diabetes mellitus.
Diabetes Care
PMID:Sulfonylurea effects on target tissues for insulin. 637 28

This study was undertaken to examine the effect of fibrin stabilizing factor (F.XIII) on healing of bone defects in normal and uncontrolled diabetic rats. Eighty rats were divided into two groups: group I (diabetic) and group II (non-diabetic) (40 rats each). Diabetes was induced in group I using streptozotocin. Both groups were divided into two subgroups, control and experimental (20 rats each). Bone defect was created in the mandible. Rats in the experimental subgroups were injected with F.XIII, while those of the control groups were injected with saline (F.XIII solvent). Animals were killed at varying intervals and tissue sections stained with hematoxyline and eosin and Van-Gieson stains were examined. Differences in collagen deposition and bone formation were compared in both control and experimental groups. Collagen deposition was evident and appeared more oriented in diabetic rats treated with F.XIII, and signs of bone deposition started in the experimental group earlier than in the control group. On the other hand, F.XIII did not significantly affect healing in non-diabetic rats. It is concluded from these results that F.XIII may enhance early stages of bone healing in uncontrolled diabetic rats.
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PMID:The effect of fibrin stabilizing factor (F.XIII) on healing of bone defects in normal and uncontrolled diabetic rats. 1041 1

Type 1 diabetes and celiac disease are both immunologic disorders where specific HLA alleles are associated with disease risk. We have developed a radioassay for autoantibodies to tissue transglutaminase (tTG) following the report that this enzyme is 'the' endomysial autoantigen (EMA) of celiac disease. The radioassay for transglutaminase autoantibodies is similar to that utilized for detecting anti-islet autoantibodies. The 'cut-off' for the IgA autoantibody assay was established as 3 x 100th percentile of 184 healthy control subjects at an index of 0.05. Ninety-eight of 847 patients with type 1 diabetes (11.6%) had tissue transglutaminase autoantibodies (tTG). All EMA-positive patients were positive (49/49) for transglutaminase autoantibodies, as were 49/540 EMA-negative patients. Twenty transglutaminase-positive patients consented to intestinal biopsy and 15 biopsies were positive for celiac disease. All patients with a transglutaminase level greater than 0.70 (13/13) had a positive biopsy, while none (0/3) with a level <0.3 had a positive biopsy. The prevalence of transglutaminase autoantibodies was higher in diabetic patients with HLA DQ2 or DQ8. One third of DQ2 homozygous patients (22/68) expressed transglutaminase autoantibodies vs. less than 2% of patients lacking DQ2 or DQ8. A simple radioassay for IgA transglutaminase autoantibodies detects all endomysial antibody positive patients and detects transglutaminase autoantibodies in 5% of endomysial autoantibody negative patients. The prevalence of transglutaminase autoantibodies is associated with DQ2 and DQ8 and in particular DQ2 homozygosity. Autoimmunity to transglutaminase is remarkably prevalent amongst patients with type 1 diabetes expressing certain class II HLA alleles.
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PMID:One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease-associated transglutaminase autoantibodies. 1044 Nov 79

Gliadin antibody (GA) tests used in screening for coeliac disease (CD) frequently yield positive GA results without accompanying CD in cases of diabetes mellitus type 1 (DM-1). To enlighten this phenomenon we screened 848 DM-1 patients for IgA- and IgG-GA. Subsequently, 16 out of 19 high titre GA patients (6 with CD) were compared with 37 low titre DM-1 patients matched for sex, age and disease duration, for autoimmune and immunogenetic markers. Chronic thyroiditis and thyroid peroxidase (TPO) antibody positivity were more frequent in the GA-positive than in the GA-negative sub-group (38 vs. 2.7%, p = 0.003, and 69 vs. 27%, p < 0.00, respectively). The tissue transglutaminase (tTg) IgA titres correlated with CD but not with GA. tTg IgG titres were lower in GA-positive individuals (p = 0.0012). GA-positivity correlated with a higher titre of factor XIII IgA antibodies (p < 0.001). GA-positive DM-I patients were characterised by a distinct immunogenetic profile; the risk of HLA DQB1*02 was lower among GA-positive patients than among GA-negatives (OR 0.4, preventive fraction 0.43). All CD patients were HLA DRB1*03-DQB1* 02-positive, but none of the five patients with normal biopsies. GA-positive patients instead had HLA DRB1*13 in 37.5% as compared to 8.6% in GA-negative (OR 6.4, etiologic fraction 0.32). Thus, the occurrence of positive GA in DM-1 is correlated to TPO antibody positivity, thyroiditis and factor XIII IgA antibodies, but inversely correlated to tTg IgG, and seems to be associated with another HLA haplotype than that previously found to be associated with CD.
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PMID:Gliadin antibodies in adult insulin-dependent diabetes--autoimmune and immunogenetic correlates. 1119 Dec 81


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