Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Purified carrier-free 125I-Tyr insulin (125I-Tyr Ins) was injected into the vitelline vein of rat fetuses in utero after 17, 19, or 21 days of gestation. Three minutes later, a radioactivity concentration index (RCI) was calculated by dividing the specific activity of each organ by that of the feto-placental unit. The highest RCI were found in the liver (4.09, 5.97, and 6.48, respectively after 17, 19, and 21 days of gestation). Binding of 125I-Tyr Ins to the liver was inhibited by coinjection of excess unlabeled insulin. Sequential injections of 125I-Tyr Ins followed by excess unlabeled insulin demonstrated that 125I-Tyr Ins binding to the liver was but partly reversible and allowed us to calculate that the half-life of the tracer in the whole body receptor compartment was 6 min in 21-day postcoitum fetuses. After extraction and chromatographic analysis, liver radioactivity appeared composed of undamaged 125I-Tyr Ins and low mol. wt. degradation products (125I- and 125I-tyrosine). Liver maturation was characterized by an enhanced capacity to degrade 125I-Tyr Ins and to expel low mol. wt. radioactive products out of the cells. Autoradiographic studies demonstrated that 125I-Tyr Ins was bound in a saturable manner to the hepatocytes and, to a lesser extent, to the liver hematopoietic cells. Three minutes after the tracer alone, silver grains were predominantly associated with the hepatocytes' plasma membranes. Later, the percentage of internalized grains increased. Because the percentage of liver radioactivity identified as low mol. wt. radioactive products was always smaller than that of internalized silver grains, true 125I-Tyr Ins was actually internalized in the hepatocytes. The rate of 125I-Tyr Ins translocation from the membrane into the cytoplasm increased with the degree of liver maturity. It is concluded that during the last 5 days of gestation, liver maturation concerns insulin internalization and degradation, i.e., postreceptor steps rather than receptor ontogenesis.
Diabetes 1982 Jan
PMID:Maturation of liver handling of insulin in the rat fetus. 675 14

Rat pancreatic islets were incubated in vitro with L-[4,5-3H]leucine or with L-[2,3-3H]tryptophan in Krebs-Ringer bicarbonate buffer, containing 0, 5, or 20 mM glucose. Incorporation of labeled amino acids in islet cells was evaluated quantitatively by a validated radioautographic procedure. Incorporation of labeled leucine into [3H]proinsulin and [3H]insulin was measured by immunoprecipitation and into other islet proteins by trichloroacetic acid precipitation. Incorporation of labeled amino acids in pancreatic beta cells was patchy and not uniform. Up to 20 to 35% of beta cells, mainly in central regions of the islets, showed poor or no incorporation of label. Peripheral nonbeta, endocrine islet cells and mesenchymal islet cells were all uniformly labeled. Incorporation of either amino acid into nonbeta endocrine and mesenchymal cells was not much affected by the absence of glucose in the incubation buffer. In contrast, incorporation of the amino acids into beta cells was strikingly affected. Incorporation of [3H]leucine into proinsulin and insulin at 0 mM glucose measured by specific immunoprecipitation and by silver grain densities over beta cells was 15 to 20 times less than at 20 mM glucose. Incorporation of [3H]tryptophan, an amino acid absent in proinsulin, into nonhormonal, sedentary beta cell proteins studied by radioautography, similarly, was strikingly affected in the absence of glucose. Thus, radioautography revealed a great sensitivity of both hormonal and nonhormonal protein biosynthesis in the beta cell to the concentration of glucose in the medium.
Diabetes 1980 Oct
PMID:Biosynthesis of proinsulin and other islet cell proteins in pancreatic beta cells of the rat: a radioautographic evaluation of glucose effects in vitro. 700 60

Rats were infused for brief periods with buffer, glucose, or insulin. L-[4,5-3H] leucine (2.5 mCi) or L-[2,3-3H]-tryptophan (0.5 mCi) was quickly injected intravenously 30 min after the onset of the infusion, when marked hyperglycemia or hypoglycemia had been established. Rats remained connected to the infusion system and were killed 30 min after the injection of the labeled amino acid. Pancreatic islets were isolated by enzymatic digestion of the pancreas. They were processed for radioautography or for the measurement of [3H] proinsulin and [3H] insulin by immunoprecipitation and of other islet [3H] proteins by TCA precipitation. Various tissues of the rats were also removed to measure TCA-precipitable-labeled proteins. Incorporation of [3H]-leucine into proinsulin and insulin was 9 to 20 times greater in the hyperglycemic than in the hypoglycemic rats. Incorporation of [3H]-tryptophan into sedentary beta-cell proteins, measured by thea density of silver grain in radioautographs, showed a sixfold difference. The great sensitivity of hormonal and nonhormonal protein biosynthesis of the pancreatic beta cell to plasma glucose was unique among tissues and among other pancreatic islet cells we studied.
Diabetes 1980 Oct
PMID:In vivo incorporation of [3H[ leucine and [3H] tryptophan into proinsulin-insulin and other islet cell proteins in normoglycemic, hyperglycemic, and hypoglycemic rats. 700 61

Diagnostic criteria for allergic fungal sinusitis have not been established, and clinical information consists primarily of isolated case reports. We proposed five diagnostic criteria for allergic fungal sinusitis including: (1) the demonstration of the characteristic eosinophil-rich allergic mucin visually or histopathologically, (2) a positive fungal stain or culture from the sinus at surgery, and (3) the absence of immunodeficiency or diabetes. With these criteria, seven patients in our metropolitan area with allergic fungal sinusitis were identified in a short period. Initial symptoms in our seven patients reflected those in 99 case reports in that two children were first seen with proptosis, one child and three adults with nasal congestion, and one adult with symptoms of chronic sinusitis. All had pansinusitis as shown on x-ray films. Six patients were atopic, five had nasal polyposis, and five had Curvularia species cultured from the sinuses. Infections with Bipolaris species, asthma, and chronic sinusitis were less common in our patients than in those previously reported. Recurrent symptoms and additional surgery sometimes resulted when the diagnosis was delayed by failure to obtain silver stains for fungus on surgical material sent for histopathologic review. Sinus tomography showed that the fungal material in the sinuses was of high density, which distinguished it from polyps or bacterial exudate. Bony compression, erosion, and rupture of the sinus walls were common. Results of IgE levels, precipitin determinations, and eosinophil counts were variable in both our patients and those in the literature. On the basis of our review, we believe that the simple diagnostic criteria proposed are appropriate for both research and clinical purposes.
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PMID:Diagnostic criteria for allergic fungal sinusitis. 762 60

The present clinical evaluation of fetal lung maturity relies largely on the determination of the amniotic surfactant phospholipids phosphotidylglycerol, lecithin, and sphingomyelin, but there are many false negatives as well as false positives among diabetics. The use of other components of lung surfactant, namely, the hydrophobic surfactant proteins (SPs) has long been suggested as an alternative to the classical assay, but tests based on the detection of immunoreactive SP-A have not proved superior or supplanted phospholipid ratios as an index. This report investigates the proteins in a fraction of third-trimester human amniotic fluid (the particulate fraction) enriched in the SP complexes that form the surfactant monolayer. The proteins were analyzed by two-dimensional polyacrylamide gel electrophoresis and visualized by silver staining and immunoblotting. Eight proteins are of particular interest. Three novel proteins (termed AFPP-1, AFPP-4, and AFPP-8) and the alpha-fetoprotein/human serum albumin complex (AFPP-7) can be detected throughout the 28- to 38-week gestational window. The protein that is referred to as AFPP-2 could be identified as SP-A on the basis of immunologic cross-reactivity as well as size and charge characteristics. The time course of appearance of AFPP-2 was also followed in patients with Rh isoimmunization syndrome and was found to be the same as that seen for SP-A. The SP-A was detected as at least five major charged isoforms with multiple subisoforms of different molecular weight and can be distinguished from a related set of proteins (AFPP-5) that appear with a different time course but are possible precursors. Two other proteins (AFPP-3, AFPP-6), which are detectable inconsistently bear some similarity to others reported previously but not extensively characterized. These results define both constant and variable proteins of the particulate fraction of the amniotic fluid and indicate that certain protein isoforms are changing throughout the third trimester. These data enhance the possibility of the utilization of these proteins as markers of lung maturity in conditions such as maternal diabetes.
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PMID:Marker proteins in the particulate fraction of third-trimester amniotic fluid. 772 75

We have previously demonstrated by in situ hybridization and Northern blot analysis that alveolar type II cells and nonciliated bronchiolar epithelial (Clara) cells in lungs of rats with diabetes have decreased surfactant protein A (SP-A) but increased mRNA. In the present study, we have examined the mRNA expression and localization of two hydrophobic surfactant proteins, SP-B and SP-C, and have compared them with SP-A mRNA levels and cellular localization in streptozotocin-induced diabetic lungs. Localization and level of expression were analyzed by in situ hybridization using type-specific, surfactant cDNA probes. Diabetes was induced in adult rats by an intraperitoneal injection of 60 mg/kg streptozotocin. Ten weeks after injection, higher numbers of silver grains representing SP-A and SP-B mRNAs were observed in alveolar type II cells of diabetic lungs, compared with control lungs. Moreover, the number of silver grains representing SP-C mRNA decreased in alveolar type II cells from diabetic lungs compared with controls, and no silver grains for SP-C mRNA were present in bronchiolar epithelial cells from either control or diabetic groups. In contrast, in bronchiolar epithelial cells of diabetic lungs, the relative abundance of silver grains for SP-A mRNA increased approximately 2-fold above controls, while SP-B mRNA decreased slightly. Taken together, there is differential expression in the level of SP-A, SP-B, and SP-C mRNAs in both alveolar and bronchiolar epithelial cells from diabetic lungs when compared with control lungs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential expressions of surfactant protein SP-A, SP-B, and SP-C mRNAs in rats with streptozotocin-induced diabetes demonstrated by in situ hybridization. 791 8

Postnatal development of islet cells was morphometrically studied during neonatal (0, 1, 3, 5, and 7 days post partum << p.p. >>) and adult periods in Wistar and Sprague-Dawley rats, using two sensitive immunostainings, immunogold silver and protein A gold silver techniques. Nonfasted and fasted plasma glucose levels were also measured in adults. In addition, the frequency of developing type 2 diabetes was surveyed following injection of streptozotocin to neonates (2 days p.p.) of Wistar and Sprague-Dawley rats. The following results were obtained: 1) Islets grew more rapidly in Wistar than in Sprague-Dawley rats; 2) Increased percent areas of A and D cells and decreased percent area of B cells occurred during neonatal period in both Wistar and Sprague-Dawley rats; 3) Higher percent area of A cells and lower percent area of B cells were observed in Sprague-Dawley than in Wistar rats; 4) The duodenal pancreas of Wistar rats exhibited a marked neonatal increase in the percent area of pancreatic polypeptide (PP) cells and; 5) Sprague-Dawley rats were more susceptible to streptozotocin-induced type 2 diabetes, as compared with Wistar rats. An assumption is proposed that the differences in islet cell development between these rat strains are reflected in diabetes morbidity data.
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PMID:A morphometrical study of the postnatal development of rat pancreatic islets, with special regard to the differences between Wistar and Sprague-Dawley strains. 833 33

Distribution of protein zero (P0) and myelin basic protein (MBP) mRNAs in the sciatic nerve from rats with alloxan-induced diabetes was analyzed at two different time points using in situ hybridization. Some animals of each diabetic group were treated with insulin. Densitometric quantitation of silver clusters revealed that 5 weeks after diabetes induction P0 mRNA only is significantly increased, while at 14 weeks both P0 and MBP mRNA contents are markedly higher than controls. Insulin treatment normalizes glycemia levels and slightly counteracts increased P0 mRNA at both stages of diabetes. An increase in MBP mRNA is observed in chronic diabetic animals only, and is unaltered by the normoglycemic effect of insulin. The increased transcript levels of P0 and MBP suggest that Schwann cells can modulate gene expression of myelin-specific proteins in response to diabetic-induced metabolic derangement. Such a change may represent a higher turnover of myelin proteins as an attempt by the Schwann cells to repair the diabetes-induced nerve damage. The observed pattern of transcript amount is only slightly influenced by insulin treatment.
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PMID:In situ hybridization study of myelin protein mRNA in rats with an experimental diabetic neuropathy. 871 Feb 12

Major complications arising from diabetes mellitus include neuropathic pain and altered peripheral inflammatory responses. Somatostatin (SOM), calcitenin gene-related peptide (CGRP), and substance P (SP) are neuropeptides that modulate pain responses transmitted by primary sensory afferents, the cell bodies of which are located in the dorsal root ganglion (DRG). Thus, the goal of the present study was to determine whether the diabetic condition is associated with altered neuropeptide gene expression in lumbar DRG of the rat. We employed an established animal model in which streptozotocin (STZ, 55 mg/kg) is administered to 6 week-old rats. The hallmark symptoms of hyperglycemia (blood glucose > 400 mg/dl), polydipsia, polyuria, and severe weight loss were maximal at 6 weeks postadministration, at which time animals were sacrificed. For determination of peptide encoding mRNAs distributed in DRG neurons, in situ hybridization histochemistry utilizing S-end-labeled oligonucleotides complimentary to sequences of preprosomatostatin (PPSOM), preprocalcitonin gene related peptide (PPCGRP), preprotachykinin (PPT), or preproneuropeptide Y (PPNPY) mRNA was performed. Silver grains were detected overlying DRG cells by autoradiography on sections of tissue counterstained with thionin. Semiquantitative analysis of differences in silver grain signal were made using an image analysis system, which expressed signals as fCi/microns2. In diabetic rats there was a significant decrease in DRG PPSOM (54%, p < 0.01), and PPCGRP (33%. p < 0.05) mRNA hybridization from the normal values PPT mRNA hybridization signal and SP-like immunoreactivity were not significantly changed in diabetic rat DRGs compared to control. In contrast, there was an increase in the number of cells labeled with PPNPY hybridization in DRG from diabetic rats. These data suggest that CGRP and SOM synthesis in primary sensory neurons is reduced in STZ-induced diabetic rats. These changes could contribute to the painful neuropathies and altered inflammatory responses seen in diabetes mellitus.
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PMID:Streptozotocin-induced diabetes is associated with altered expression of peptide-encoding mRNAs in rat sensory neurons. 889 22

A role for glycation in diabetic pathology appears beyond doubt and one of the present trends is to focus the poorly explored field of intracellular glycation. In this work we studied the pattern of early glycation in hepatocyte cytosolic proteins from streptozotocin-induced diabetic rats (n=14) compared to control animals (n=8). Glycated proteins were present in the cytosol of control rats and increased three-fold after one month of diabetes, while glycated Hb and glycated plasma proteins rose two- and three-fold, respectively. A good correlation (r=0.82, p<0.001) was found between glycated cytosolic proteins and glycated plasma proteins, suggesting the latter could provide an indirect indication of intracellular glycation. Using PBA affinity chromatography followed by SDS-PAGE we detected 7 major glycated bands in cytosols from control animals which increased dramatically in diabetic rats. Moreover, other glycated proteins, which were undetectable in control animals, became prominent, and more than 15 major bands can thus be resolved. No major differences in the patterns can be seen after 1, 5, or 12 months of diabetes, suggesting that early glycation in cytosolic proteins reaches an equilibrium in a short period of one to two weeks (further supported by the tight correlation with glycated plasma proteins). Through comparison of the patterns obtained with an antiglucytollysine antibody on Western blots with those of silver stained gels from the PBA eluates we present evidence that intracellular glycation is mediated by glucose but mainly by other sugars.
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PMID:Glycation of hepatocyte cytosolic proteins in streptozotocin-induced diabetic rats. 895 99


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