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

Erythrocyte membrane composition was studied in rats subjected to experimental hyperlipidemia and/or hyperglycemia by means of 6 weeks of high fat (40% w/w)-high cholesterol (5% w/w)diet with and without 8 weeks of streptozotocin-induced diabetes. High fat-high cholesterol diet lowered plasma glucose levels in control and in diabetic animals. While the atherogenic diet produced only hypercholesterolemia, the same diet fed to diabetic animals produced both hypercholesterolemia and hypertriglyceridemia. The membrane protein content was lower in diabetic rats than in controls, while the cholesterol and phospholipids were higher in diabetic rat erythrocyte membranes. Feeding the atherogenic diet increased membrane lipid levels in only nondiabetic animals. The total carbohydrate content of the membranes was greater in diabetic animals than controls. Difference in relative proportion of individual sugars, e.g., galactose, mannose, glucose, and fucose of the membranes was observed between diabetic and control groups. These observations suggest that rat erythrocyte membrane composition is altered both in hyperglycemic and hyperlipidemic conditions, and may provide a useful model for evaluating lipid carbohydrate abnormalities of membrane structures in diabetes mellitus.
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PMID:Effects of diabetes and high fat-high cholesterol diet on plasma lipid levels and on erythrocyte membrane composition. 646 53

In experimental diabetes, a number of intestinal brush-border hydrolases and transport systems are stimulated. In this study, we assessed possible effects of diabetes on the composition and membrane fluidity of rat intestinal brush-border membranes that might correlate with these functional changes. We found similar proportions of lipid and protein in the diabetic and control preparations, although there was a considerable increase in total membrane from the diabetic rats, presumably reflecting mucosal hyperplasia. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane protein revealed an increase in the bands corresponding to sucrase-isomaltase, consistent with an increased enzyme activity of sucrase. Membrane lipid analysis revealed only a decrease in fatty acids of the neutral lipid fraction of diabetics--a change that may well have occurred during membrane preparation. 1-6-Diphenyl-1,3,5-hexatriene fluorescence polarization data, obtained as a function of temperature, was similar for the diabetic and control rats, with a three-phase linear model superior to one- and two-phase linear or quadratic models. The overall composition of the intestinal brush-border membrane, unlike other plasma membranes, appears little affected by experimental diabetes.
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PMID:Intestinal mucosa in diabetic rats: studies of microvillus membrane composition and microviscosity. 662 63

The interaction of insulin with purified rat kidney cell membranes was studied with the use of 125I-insulin. The membranes showed high insulin-degrading activity which was dependent on temperature, time and membrane concentration. Specific binding of insulin was demonstrated in the presence of 0.3 mM bacitracin and was time- and temperature-dependent. 125I-insulin was displaced by native insulin, AI-B29 dodecoyl insulin and proinsulin in proportion to their relative bioactivity. Kidney membranes isolated from streptozotocin-diabetic rats bound more insulin per mg of membrane protein (approx. 65%) than did membranes of control animals. Scatchard analysis indicated that this increase in binding was due to an increased binding capacity rather than an increased affinity for insulin. Injection of diabetic rats with insulin resulted in a decrease of insulin binding when compared with the untreated diabetic animals. Diabetes also resulted in altered kinetics of insulin degradation.
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PMID:Insulin binding and degradation by kidney cell membranes of streptozotocin-diabetic rats. 674 31

The effects of high-fat/low-carbohydrate feeding on glucose transport activity and on the concentrations of glucose transport systems in the plasma and low-density microsomal membranes in isolated rat adipose cells have been examined. Glucose transport activity was assessed by measuring 3-O-methylglucose transport and the concentration of glucose transport systems estimated by measuring specific D-glucose-inhibitable cytochalasin B-binding. Basal glucose transport activity is not significantly influenced by high-fat/low-carbohydrate relative to low-fat/high-carbohydrate feeding and is accompanied by a constant 10 pmol of glucose transport systems/mg of membrane protein in the plasma membrane fraction. In contrast, maximally insulin-stimulated glucose transport activity decreases from 4.72 to 2.29 fmol/cell/min and is accompanied by a decrease from 44 to 26 pmol of glucose transport systems/mg of plasma membrane protein. These diminished effects of insulin on glucose transport activity and the concentration of glucose transport systems in the plasma membrane fraction are paralleled by a 48% decrease in the basal number of glucose transport systems/mg of membrane protein in the low-density microsomal membrane fraction, the source of those glucose transport systems appearing in the plasma membrane in response to insulin. Thus, the "insulin-resistant" glucose transport of the adipose cell with high-fat/low-carbohydrate feeding may be the consequence of a depletion of glucose transport systems in the intracellular pool.
Diabetes 1982 Jul
PMID:A possible mechanism of insulin resistance in the rat adipose cell with high-fat/low-carbohydrate feeding. Depletion of intracellular glucose transport systems. 676 Nov 96

The modification of haemoglobin A by glucose to haemoglobin A Ic is a classical example for a nonenzymatic glucosylation (n. e. glu.) reaction of a protein. It has been suggested, that various proteins are subjected to this process during hyperglycemia phases, if the protein meets certain steric, electrostatic and biochemical characteristics. In the present report n. e. glu. of haemoglobin, serum protein, collagen, basement membrane protein and alkaline phosphatase is discussed. It is suggested that n. e. glu. might influence protein function and forms thus the biochemical basis for specific complications of diabetes mellitus in an outside pregnancy.
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PMID:[Non-enzymatic glucosylation of proteins]. 709 97

To investigate abnormalities in peripheral nerve myelin in experimental diabetes, we studied the effects of the proteolytic enzymes trypsin and alpha-chymotrypsin on the proteins of this membrane, obtained from the sciatic nerves of normal rats and from animals made diabetic with streptozotocin. The dominant effect of the proteolytic enzymes was to incompletely degrade the major membrane protein (mol. wt. 28,000), with the appearance of new protein (mol. wt. 20,000). Using myelin isolated from the nerves of diabetic animals, the reaction was approximately one-half that of the controls (P less than 0.01) for both enzymes. When, however, the myelin protein affected by trypsin and chymotrypsin was isolated from the membrane and then incubated with the proteolytic enzyme, its proteolysis was complete and took place at the same rate in the diabetic animals and controls. These findings suggest that, in this model of experimental diabetes, there is an alteration in the structure of peripheral nerve myelin that inhibits interaction between the protein in the membrane bilayer and two water soluble proteolytic enzymes. This alteration could not be demonstrated in protein isolated from the membrane, suggesting that the change relates to the interaction of the protein and other components of myelin, rather than to chemical alteration in the protein per se.
Diabetes 1981 Apr
PMID:Effect of experimental diabetes on the susceptibility of myelin proteins to proteolysis. 720 63

The effect of chronic streptozotocin-induced diabetes was studied on intestinal microvillous membrane surface carbohydrate groups. After 7 weeks of diabetes, purified microvillous membranes were prepared from rat small intestine and surface galactoproteins identified by labeling with galactose oxidase/sodium boro[3H]hydride. Membrane surface sialic acid residues were labeled using the sodium metaperiodate/sodium boro[3H]hydride technique. Membranes were solubilized in SDS and protein labeling analyzed by acrylamide electrophoresis. Membranes from diabetic rats showed an 81% increase in galactoprotein labeling (P less than 0.02) while labeling of sialic acid residues was unchanged. The greatest increase in galactoprotein labeling occurred in protein monomers of Mr 116,000-200,000, where there was a 155% increase in labeling (P less than 0.005). These results indicate that intestinal microvillous membrane protein glycosylation is altered in chronic diabetes. This increase in surface membrane carbohydrates could explain the decreased rates of proteolytic degradation previously described for at least one microvillous protein. An increase in membrane galactose groups has also been noted in hepatocyte and kidney glomerular basement membranes, which suggests the presence of a systematic change in membrane protein glycosylation occurring as a result of the diabetic state.
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PMID:Alterations in labeling of cell-surface glycoproteins from normal and diabetic rat intestinal microvillous membranes. 731 89

The majority of patients with insulin-dependent diabetes (IDDM) have Abs to 40- and/or 37-kDa tryptic fragments (37/40K-Abs) deriving from an unidentified islet cell membrane protein distinct from glutamate decarboxylase (GAD). Recently, autoantibodies against ICA512, which has identity with the protein tyrosine phosphatase-like protein IA2, were reported. In this study we have examined whether IA2/ICA512 is the Ag specificity of 37/40K-Abs, and one of the determinants of islet cell Abs (ICA) detected by immunofluorescence. Serum from 51 of 100 new onset IDDM patients immunoprecipitated 40- and/or 37-kDa insulinoma polypeptides, and 53 immunoprecipitated in vitro translated rIA2; 49 had both 37/40K-Abs and rIA2 Abs. There were strong correlations between the levels of Abs to rIA2 and both 40 kDa (r = 0.85, p < 0.0001) and 37 kDa (r = 0.70, p < 0.0001) insulinoma polypeptides. Trypsin treatment of immunoprecipitated rIA2 yielded 40- and 37-kDa fragments, and preincubation of sera with rIA2 completely inhibited binding to the insulinoma 40- and 37-kDa polypeptides. IA2 Ab levels also correlated with ICA titer in GAD-Ab negative sera, and preincubation with rIA2 reduced ICA staining intensity in sera with ICA and IA2 Abs, but not in sera with ICA in the absence of IA2 Abs. These results provide clear evidence for the identification of IA2/ICA512 as the precursor of the islet 40- and 37-kDa polypeptide autoantigens and as one of the ICA specificities. Combined detection of Abs to IA2 and GAD65 in a single radio-binding assay identified Abs in 88 of 100 IDDM patients, and potentially facilitates population screening for IDDM risk assessment.
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PMID:Identification of protein tyrosine phosphatase-like IA2 (islet cell antigen 512) as the insulin-dependent diabetes-related 37/40K autoantigen and a target of islet-cell antibodies. 759 59

Goto-Kakizaki (GK) rat, a rodent model of spontaneously occurring non-insulin dependent diabetes mellitus (NIDDM), exhibits impaired glucose-stimulated insulin secretion. To explore the background of the beta-cell dysfunction in NIDDM, we investigated whether and how the expression pattern of factors that would potentially be involved in the glucose-stimulated insulin secretion machinery is changed in GK rats. Using quantitative reverse transcription-PCR (RT-PCR) method, we found that the gene expression of CD38, a type 2 membrane protein which has ADP-ribosyl cyclase activity, is reduced by approximately 50% in islets of GK rats. Despite previous studies showing reduction in the FAD-linked mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) activity in GK rats, the mGPDH mRNA amounts were equal to those in the control Wistar rats, suggesting a difference that arose post-transcriptionally. These observations support the idea that multiple defects of the glucose-responsive insulin secreting machinery are involved in the development of diabetes in GK rats.
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PMID:Expression of CD38 gene, but not of mitochondrial glycerol-3-phosphate dehydrogenase gene, is impaired in pancreatic islets of GK rats. 766 44

A major pathological feature of noninsulin-dependent diabetes (NIDDM) is defective insulin-stimulated glucose transport in skeletal muscle. When NIDDM subjects are assessed as a group, GLUT4 gene expression in skeletal muscle varies widely and is not different from that in controls. Thus, longitudinal studies are needed to assess whether changes in GLUT4 expression in muscle of NIDDM subjects could be responsible for changes in glucose disposal. The question is timely because recent studies in transgenic mice show that increasing GLUT4 expression can increase insulin-stimulated glucose uptake in vivo and in vitro. Here we use a longitudinal design to investigate the effects of 8 weeks of therapy with the sulfonylurea gliclazide on glycemic control, glucose tolerance, insulin-stimulated glucose disposal, and GLUT4 expression in muscle of 10 obese NIDDM subjects. Subjects were on a weight-maintaining diet. Gliclazide treatment results in increased serum C-peptide, decreased hemoglobin-A1c, decreased glucose excursion on glucose tolerance test, and 35% increased insulin-stimulated glucose disposal. Gliclazide therapy is not associated with any change in DNA or protein content per g muscle or any alteration in GLUT4 levels expressed either per microgram membrane protein or per DNA. In summary, the improvement in glycemic control and glucose disposal in NIDDM subjects receiving gliclazide therapy cannot be explained by increased expression of GLUT4 in muscle. Thus, therapeutic effects on insulin-stimulated glucose disposal can be achieved in NIDDM subjects without altering GLUT4 expression in muscle.
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PMID:Sulfonylurea therapy improves glucose disposal without changing skeletal muscle GLUT4 levels in noninsulin-dependent diabetes mellitus subjects: a longitudinal study. 782 24


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