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

Mammalian liver possesses a unique isozyme of phosphate-activated glutaminase which plays an important role in the regulation of glutamine catabolism. Antibodies to hepatic glutaminase were used to screen a lambda gt11 rat liver cDNA library. One cDNA to hepatic glutaminase was identified. Changes in the relative abundance of hepatic glutaminase mRNA were determined by hybridization to this cDNA. The mRNA is found only in liver; it is not present prior to birth but its abundance increases dramatically at birth. The abundance of the mRNA is increased approximately 4-fold in diabetes. The sequence of the cDNA was compared to that recently published for kidney (brain)-type glutaminase (Banner, C., Hwang, J.-J., Shapiro, R.A., Wenthold, R.J., Nakatani, Y., Lampel, K.A., Thomas, J.W., Huie, D., and Curthoys, N.P. (1988) Mol. Brain Res. 3, 247-254). When the predicted amino acid sequences were compared a region of 123 amino acids with greater than 80% identity was found. The presence of scattered amino acid substitutions within stretches of identical amino acids suggests that the glutaminase isozymes are encoded by separate genes. This is the first demonstration of any similarity between the two glutaminases at the molecular level.
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PMID:Molecular cloning of a cDNA for rat hepatic glutaminase. Sequence similarity to kidney-type glutaminase. 219 54

Evidence from epidemiological and histopathologic studies in humans with autoimmune type 1 (insulin-dependent) diabetes suggests that beta-cell destruction within the islets of Langerhans progresses through a number of stages. In this review we draw on recent experimental evidence in an attempt to define the molecular pathology of these stages. Stage 1 is postulated to be initiated by modification of the beta cell by virus, chemical or other factors, leading to the production of interferon-alpha, hyperexpression of major histocompatibility complex (MHC) class I molecules and induction of MHC class II molecules. Experiments in transgenic mice suggest that overexpression of MHC molecules is in itself detrimental to beta-cell function. Shedding of antigen(s) from dying beta cells in combination with hyperexpression of MHC molecules may be a powerful immunogenic stimulus. Stage 2 commences with infiltration of the islets by immuno-inflammatory cells (termed insulitis). It is proposed that production of cytokines from the infiltrating cells induces "phenotypic switching" in beta cells, with further upregulation of MHC molecules and the induction of intracellular adhesion molecule-1 expression and interleukin-6 production. Together, these properties are seen as a prerequisite for the presentation of autoantigen by beta cells to adherent T lymphocytes and autoimmune activation. The final stage encompasses autoimmune-mediated destruction of the beta cells by the targeted delivery of cytotoxic cytokines and other mediators.
Mol Biol Med 1990 Aug
PMID:Molecular pathology of type 1 diabetes. 223 44

The adhesion of leukocytes to endothelium is a physiological phenomenon which is the first step for leukocyte emigration. The adhesion can be dramatically increased in pathological situations such as inflammation and vascular diseases. The molecular basis of leukocyte-endothelium interaction has been largely investigated in the last ten years. Using monoclonal antibodies it is possible to characterize the leukocyte adhesion molecule (LeuCAM) also named CD11/CD18 complex. These molecules responsible for leukocyte adhesion are heterodimers consisting of a common beta subunit and different subunit CD11a/CD18 corresponding to LFA-1; CD11b/CD18 to Mac1/Mol; CD11c/CD18 to GP150-95. Beside these receptors, other leukocyte structures such as the fibronectin receptors are involved in the adhesive process. On the endothelial cell side specialized structures implicated in leukocyte adhesion have been identified. Structures like Intercellular Adhesion Molecule (ICAM) are expressed on endothelial cells in the absence of stimulation, while other receptors Endothelial Leukocyte Adhesion Molecule (ELAM) are only detectable on activated endothelial cells. Cytokines such as IL-1 induced the expression of ELAM, increased the number of ICAM and Human Leukocyte Antigens (HLA) DR, DP, DQ. In various pathological circumstances, namely extracorporeal circulation, Acute Respiratory Distress Syndrome (ARDS), hypercholesterolemia and diabetes mellitus increased leukocyte adhesion has been reported and is potentially responsible for vascular damage. Therefore, the modulation of leukocyte-endothelial cell interactions is a possible target for antithrombotic and antiatherosclerotic therapy.
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PMID:Leukocyte adhesion to endothelial cells. 226 8

The structure and the regulatory mechanisms of insulin gene expression as well as the structure of the 5'-regulatory region of its gene are reviewed. Protein binding sites of the 5'-enhancer area of the insulin gene were identified by methods of site mutation, footprinting and competitive amplification in several papers. Diabetes induced by site mutation of the insulin gene is considered. Some viruses and viral proteins suppress the regulatory region of the insulin gene and induce diabetes symptoms. Transgenic animals carrying the natural human insulin gene together with the 5'-regulatory sequence in their genome show elevated human insulin and C-peptide secretion in response to high blood glucose concentration. The insulin receptor gene structure and mechanisms of insulin receptor functioning are discussed.
Mol Biol (Mosk)
PMID:[Recombinant DNA in the study of diabetes mellitus]. 229 Apr 17

The degu, Octodon degus, is a South American hystricomorph rodent that is of interest because it develops spontaneous diabetes mellitus and has been found to have islet amyloidosis. To help clarify these problems we have cloned cDNAs encoding islet amyloid polypeptide (IAPP), insulin, and glucagon precursors from this species. The predicted amino acid sequence of degu IAPP is very similar to that of nonamyloid-forming guinea pig IAPP. In contrast, degu insulin and the C-terminal region of degu glucagon are highly divergent from those of other mammals, as is also the case in the guinea pig, suggesting the existence of some form of positive evolutionary pressure on these hormones of carbohydrate metabolism in the hystricomorph rodents.
Mol Endocrinol 1990 Aug
PMID:Cloning of complementary DNAs encoding islet amyloid polypeptide, insulin, and glucagon precursors from a New World rodent, the degu, Octodon degus. 229 24

Two insulin genes of the NON mouse, an animal model of human non-obese, non-insulin-dependent diabetes mellitus, were isolated and characterized to examine the hypothesis that these genes are structurally different from those of normal mice. The NON mouse was found to have two non-allelic insulin genes, as does the normal mouse, and no structural differences were found between the normal and NON mouse in the nucleotide sequence of the insulin gene, including that of the 5'-transcriptional regulatory region, and in the deduced amino acid sequence. There was, however, an additional 113 bp sequence and seven point mutations in a further 5'-flanking region, and three point mutations in the 3'-flanking region of the insulin II gene. We conclude that reduced expression of insulin genes in the NON mouse is not due to the structural change in the known transcriptional regulatory region, although the effect on insulin II gene expression of an additional sequence upstream of the 5'-flanking region, as the negative regulatory factor, remains to be elucidated.
J Mol Endocrinol 1990 Aug
PMID:Molecular cloning and DNA sequence analysis of preproinsulin genes in the NON mouse, an animal model of human non-obese, non-insulin-dependent diabetes mellitus. 239 23

Aldose reductase (AR), an enzyme that catalyzes the conversion of glucose to sorbitol, has been implicated in the pathogenesis of many of the complications of diabetes mellitus, but its normal physiological function in various tissues remains uncertain. It has been suggested that in the kidney, sorbitol production may be an important cellular protection against medullary intersitital hypertonicity. Using in situ and Northern hybridization analyses, we found that at the time of birth, AR mRNA expression in the kidney was very low and seen only in the papilla. By 12 days of age, at about the time a corticopapillary osmotic gradient and the capacity for urinary concentration have developed, a striking increase in renal AR mRNA levels was seen. It was confined to the inner medulla and was characterized by a dramatic gradient of expression paralleling the corticopapillary osmotic gradient. Levels of expression were somewhat lower in adults, but showed the same inner medullary boundary and gradient. Under these hybridization and exposure conditions, no AR transcripts were detected in the outer medulla or cortex. Homozygous Brattleboro rats with congenital diabetes insipidus have relatively dilute corticopapillary osmotic gradients, and their level of medullary AR mRNA was significantly lower than that of controls. Conversely, normal rats made hyperosmotic and, hence, antidiuretic by salt loading showed a large increase in medullary AR mRNA. These changes in renal medullary AR gene expression in correlation with changes in medullary tonicity support the hypothesis that renal AR plays a role in cellular adaption to osmotic stress and suggest that local medullary osmolarity may regulate the level of AR gene expression.
Mol Endocrinol 1989 Sep
PMID:Developmental and physiological regulation of aldose reductase mRNA expression in renal medulla. 251 49

4,6-O-Ethylidene glucose (ethylidene glucose), a specific inhibitor at the outer surface of a glucose transporter in the cell membranes, substituted analogue of streptozotocin was newly synthesized. This compound did not induce diabetes in rats and also did not show cytotoxic effect on pancreatic beta cells of neonatal rats in a monolayer culture system. The reasons why such a molecule was designed and why it showed no biological effects are discussed on the basis of a structure-activity relationship. Our results afford positive evidence for the presence of a glucose transport system or a glucose transporter on pancreatic beta cells and its involvement in the action of streptozotocin on beta cells.
Mol Cell Endocrinol 1989 Apr
PMID:Ethylidene glucose-substituted new analogue of streptozotocin cannot induce diabetes: study on the basis of structure and activity relationship. 252 36

Alloxan diabetes induced in white rats by intraperitoneal injection of alloxan-monohydrate (15 mg/100 g body weight) was used to study changes in the glycogen phosphorylase a and b, phosphoprotein phosphatases and hexokinase activities under insulin deficiency conditions. Among the enzymes studied, an increase in muscle phosphorylase a activity as well as the a/b ratio have been obtained. In diabetic muscle phosphoprotein phosphatases and hexokinase activities were diminished. AMP increased the liver glycogen phosphorylase activity twice in diabetic rats whereas in normal animals the enzyme was less sensitive to this effector. The changes in liver hexokinase activity at diabetes were not connected and correlated with the altered phosphorylase and protein phosphatase activities. The logical chain of probable molecular events taking place in muscle glycogen metabolism under the conditions of insulin deficiency is offered.
Mol Cell Biochem 1989 Oct 31
PMID:Changes in the activity of enzymes, participating in glycogen metabolism of alloxan diabetic rats. 255 79

We have previously reported that rats which have been suffering from streptozotocin-diabetes for 4 weeks show a supranormal mast cell mediated mitogenesis in mesenteric windows and in the skin; this late emerging, augmented mitogenic responsiveness appears, to be unaffected by insulin per se. To test whether this increased proliferogenic response is effected by some acquired quality within the tissue rather than a systemic factor in the blood, we studied mast cell mediated mitogenesis in organ-cultured intact mesenteric windows from rats with diabetes of 4 weeks' duration, using a biochemically-defined serum-free growth medium. Mast cells were activated by Compound 48/80 and their secretion was quantified biochemically in terms of histamine release. The mast cell-dependent mitogenic reaction in the predominant, morphologically discrete fibroblasts and mesothelial cells was quantified photometrically using Feulgen-absorption analysis of individual cell nuclei, and by determination of the mitotic index. Both types of target cell responded to a significantly greater degree mitogenically in diabetic compared with control tissue. This finding suggests that a considerable part of the increased mitogenic responsiveness previously observed in diabetic animals in vivo is causally related to some tissue-bound, i.e., cellular and/or extracellular factor(s) acquired during the course of the disease.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Evidence of an acquired increase in mitogenesis in streptozotocin-diabetic rats, apparently relating to some tissue factor. 256 25


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