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)

In this study we examined the effect of experimental diabetes and of treatment with an aldose reductase inhibitor on the level of sulfation of glomerular basement membrane (GBM) heparan sulfate, the principal glycosaminoglycan in this extracellular matrix. Glycosaminoglycans were isolated from GBM purified from control, streptozocin-induced diabetic, and sorbinil-treated diabetic rats and analyzed for sulfate and uronate content. Glomerular yields from diabetic kidneys were greater than those from control animals, but the amount of sulfate per glomerulus in diabetic samples, both untreated and sorbinil treated, did not differ significantly from that in control samples. However, the sulfate-to-uronate ratio in heparan sulfate isolated from diabetic GBM (0.34 +/- 0.08) was significantly less than in control samples (0.69 +/- 0.11), and treatment of diabetic rats with an aldose reductase inhibitor did not correct this reduced ratio (0.36 +/- 0.06). The results indicate that there is an undersulfation of heparan sulfate of GBM in experimental diabetes, an abnormality that may contribute to loss of anionic sites and decreased charge selectivity of the glomerular filtration barrier. The findings further suggest that this abnormality results from disturbances in glycosaminoglycan synthesis and/or metabolism in diabetes that are independent of polyol-pathway activation in the renal glomerulus.
Diabetes 1988 Oct
PMID:Undersulfation of glomerular basement membrane heparan sulfate in experimental diabetes and lack of correction with aldose reductase inhibition. 297 Sep 80

Glucose usage by soluble fractions of cell extracts from two insulin-producing cell lines, RINm5F and HIT, was investigated. Analysis of enzyme activities indicated that glucose phosphorylation and phosphofructokinase are likely to be the rate-limiting steps of glycolysis in both RINm5F and HIT cell extracts. RINm5F extracts, which lack glucokinase, exhibited relatively flat concentration-dependency curves of glucose usage and showed substantial inhibition of hexokinase. HIT cell extracts, which contain glucokinase but lack hexokinase, exhibited sigmoidal concentration-dependency curves of glucose usage, reflecting almost fully expressed glucokinase activity. A reconstituted system prepared from RINm5F and HIT cell extracts exhibited a composite concentration-dependency curve of glucose usage and showed substantial inhibition of hexokinase and almost fully expressed glucokinase. However, conditions that activate phosphofructokinase, such as addition of ammonium sulfate or fructose 2,6-bisphosphate or alkalization, removed the inhibition of hexokinase without noticeably affecting the glucokinase component of usage. Results obtained with a reconstituted system containing RINm5F cell extract and purified glucokinase were consistent with these findings. The data presented here indicate that this reconstituted cell-free system serves as a valid model for the study of aspects of glycolytic control in the islet. This model illustrates the preeminent role of glucokinase in the control of glycolysis, consistent with its glucose-sensor function in the islet. In addition, these studies help to define the contribution of phosphofructokinase to the control of glycolysis and the mechanism whereby changes in phosphofructokinase activity could modulate, via changes in the glucose 6-phosphate concentration, the activity of hexokinase and hence the net glycolytic flux.
Diabetes 1988 Nov
PMID:Control of glucose metabolism in pancreatic beta-cells by glucokinase, hexokinase, and phosphofructokinase. Model study with cell lines derived from beta-cells. 297 77

The effect of diabetes mellitus on the interdental alveolar bone has been long debated. The present study reported the distribution of glycosaminoglycans (GAG) in normal and diabetic alveolar bone using histochemical techniques. Animals were rendered diabetic and killed at 2, 4, 6 and 9 weeks after injections. Tissues were stained with Alcian blue 8GX dye (pH 2.5) to demonstrate GAG and the intensity of the staining reactions compared with age-matched controls. During the experiment, weights of control animals did not change significantly; weights of diabetic animals were significantly less than initial weights from 0-6 weeks (p less than 0.001), but became nearly equal by 9 weeks. Staining intensity of diabetic bone demonstrated initial decrease (0-4 weeks) followed by a marked increase (4-9 weeks) suggesting an early decline in bone GAG levels followed by increased bone GAG levels as compared to age-matched control and initial levels. Bone GAG levels were significantly different between diabetics and age-matched controls at 2 (p less than 0.005) 4 (p less than 0.001), 6 (p less than 0.001) and 9 (p less than 0.001) weeks after streptozotocin injections. Digestion with chondroitinase AC, ABC and streptomyces hyaluronidase suggested significant differences between control and diabetic bone matrix in the levels of chondroitin 4 and 6 sulfates (p less than 0.05) and hyaluronic acid (p less than 0.001) but not dermatan sulfate. In control and diabetic bone, chondroitin sulfates were located within the bone matrix, dermatan sulfate within bone matrix and Sharpey fiber bundles.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proteoglycans of alveolar bone of diabetic and non-diabetic mice: a histochemical study. 298 Feb 36

The effect of diabetes on the structure and function of insulin receptors was studied in rats 7 d after streptozotocin injection, using solubilized, partially purified receptors from rat hindlimb muscles. Diabetes increased the number of insulin receptors per gram of muscle 60-70% without apparent change in insulin binding affinity. Incubation of receptors at 4 degrees C with [gamma-32P]ATP and insulin resulted in dose-dependent autophosphorylation of the beta-subunit on tyrosine residues; receptors from diabetic rats showed decreased base-line phosphorylation, as well as a decrease in autophosphorylation at maximally stimulating insulin concentrations. These receptors also showed diminished exogenous substrate kinase activity using histone H2b and angiotensin II as phosphoacceptors. The electrophoretic mobility (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) of a subpopulation of beta-subunits derived from diabetics was slightly decreased; differences in electrophoretic mobility between control- and diabetic-derived beta-subunits were enhanced by generating fragments by partial Staphylococcus aureus V8 protease digestion. Endoglycosidase-H or neuraminidase treatment increased the electrophoretic mobility of beta-subunits in both groups, but only neuraminidase appeared to decrease or abolish differences in electrophoretic mobility between controls and diabetics, suggesting that excess sialilation may account, in part, for the altered mobility of diabetic derived beta-subunits. All structural and functional alterations in insulin receptors were prevented by treating diabetic rats with insulin for 60 h. Peripheral insulin resistance associated with insulinopenic diabetes may be related to modifications in insulin receptor structure, resulting in impaired signal transmission.
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PMID:Diabetes-induced functional and structural changes in insulin receptors from rat skeletal muscle. 300 51

Angiotensin-converting enzyme, the polypeptide that converts angiotensin I to angiotensin II, was measured in the serum of 114 pregnant women who had normal blood pressure, pregnancy-induced hypertension-preeclampsia, and chronic hypertension with or without pregnancy-induced hypertension. Angiotensin-converting enzyme levels were unrelated to weeks of gestation. The angiotensin-converting enzyme levels were similar in normotensive women (21.1 +/- 6.9 units/ml), women with chronic hypertension without pregnancy-induced hypertension (23.1 +/- 2.7 units/ml), and patients with pregnancy-induced hypertension where magnesium sulfate (22.6 +/- 8.7 units/ml) had been administered prior to angiotensin-converting enzyme assay, but these values were significantly less than those in patients with pregnancy-induced hypertension with no magnesium sulfate (29.1 +/- 6.5 units/ml) therapy and in women with chronic hypertension with superimposed pregnancy-induced hypertension (30.7 +/- 4.4 units/ml) (p less than 0.005). Maternal venous and umbilical venous and arterial angiotensin-converting enzyme levels were as follows: The maternal venous level was less than the cord venous level and greater than the cord arterial value. Neither neonatal size nor twin gestation influenced the angiotensin-converting enzyme levels. Patients with diabetes mellitus had variable angiotensin-converting enzyme values regardless of the status of the blood pressure. The physiologic theories of blood pressure control in pregnant women are discussed in relation to the renin-angiotensin, bradykinin, and prostaglandin systems.
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PMID:The relation of angiotensin-converting enzyme to the pregnancy-induced hypertension-preeclampsia syndrome. 300 58

Insulin acutely inhibits the catecholamine-stimulated rise in cAMP levels in fat, liver, and muscle primarily through stimulation of the enzyme cAMP phosphodiesterase (PDE). Adipocytes from rat epidydimal fat pads were exposed to insulin and fractionated by centrifugation. Whereas the cytosolic fraction contained a low-affinity cAMP PDE that was unaffected by insulin, the activity of a high-affinity enzyme residing in a particulate fraction was increased by insulin. This enzyme activity could be solubilized with nonionic detergent and chromatographed on ion exchange followed by chromatofocusing. The resulting enzyme preparation was subjected to sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Silver staining revealed a single band with a molecular weight of 60,000. This apparent molecular weight was verified by calculation of the hydrodynamic properties of the enzyme. Evaluation of its kinetic properties indicated that the enzyme activity residing in this solubilized 60,000-Mr protein exhibited lower affinity than the membrane-bound enzyme but was still specific for cAMP. Activation of this enzyme may be one of the primary mechanisms by which insulin counteracts the effects of adenylate cyclase-stimulating hormones.
Diabetes 1986 Jun
PMID:Purification of putative insulin-sensitive cAMP phosphodiesterase or its catalytic domain from rat adipocytes. 301 73

Alkali-dissociated, purified preparations of prototype coxsackievirus B4 release a protein kinase that catalyzes the incorporation of gamma-phosphate from 32P-labeled ATP into three virus capsid proteins (VP1, VP3, VP4), several additional proteins of the particle, and exogenous acceptor proteins. Using protamine sulfate as an acceptor protein, we detected nearly 20-fold more enzyme activity in membrane-bound virions (MBV) than in virions of the virus. The activity in the MBV is cyclic nucleotide-independent, divalent cation-dependent, and has a pH optimum of 8.0. Phosphoserine is labeled with 32P. The enzyme activity sediments at about 5S and is separated into at least two peaks of heterogeneous proteins by ion-exchange chromatography. The patterns of phosphorylation by these enzyme peaks are somewhat similar. Coxsackievirus-associated protein kinase appears to be located internally in the virus and may be host-cell-coded. The enzyme appears to be lacking in a variant of the virus that produced diabetes in mice.
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PMID:Protein kinase in nondiabetogenic coxsackievirus B4. 301 40

To examine whether products of the immune system interact with the pancreatic beta-cell, rat insulinoma cells (RIN-m5F line) were cultured in the presence of conditioned medium from concanavalin A-activated mouse spleen cells (CAS medium). Indirect immunofluorescence and flow cytometry revealed that after culture in CAS medium, RIN-m5F cells had an 8- to 10-fold increase in class I major histocompatibility complex (MHC) proteins, whereas class II MHC proteins remained undetectable, and the level of insulin and/or insulin-like growth factor 1 receptors was unchanged. The stimulation of class I MHC expression on RIN-m5F cells by CAS medium could be mimicked by recombinant interferon-gamma. Analysis of 125I-surface-labeled cells by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed that in the presence of CAS medium, there was a major increase in the expression of proteins of 48,000, 32,000, and 12,000 Mr and a minor increase in proteins of 17,000 and 9,000 Mr. Precipitation with monoclonal antibody identified the 48,000- and 12,000-Mr proteins as the class I MHC protein and beta 2-microglobulin, respectively. The ability of lymphokine-conditioned medium to increase the expression of RIN-m5F cell surface proteins, including the class I MHC proteins, provides a potential mechanism for enhancing the immune-mediated destruction of the beta-cell.
Diabetes 1986 Nov
PMID:Expression of class I MHC proteins on RIN-m5F cells is increased by interferon-gamma and lymphokine-conditioned medium. 301 6

Diabetes mellitus and asthma have many antipodal features. Although both are common disorders, concurrence occurs less often than would be predicted. When co-existence does occur, the cases are generally mild, and effective treatment of one disease frequently exacerbates the other. The hypothesis is advanced that basilar membrane concentrations of heparan sulfate differ in these two diseases and that this difference may account for the antithetical features. An experimental basis for postulating increased concentrations of extracellular heparan sulfate in asthma and diminished concentrations in diabetes is cited. A rationale for tying these differences to the polar activities of cholinergic transmission and atherogenesis in the two diseases is advanced. Diminished heparan sulfate concentrations in diabetes may down-regulate the transmission of vagal impulses to insulin-producing pancreatic cells, and thereby impair both the continued vitality of these cells, and the acetylcholine modulated potentiation of glucose-induced insulin release.
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PMID:Asthma and diabetes mellitus: a biochemical basis for antithetical features. 303 19

The effects of streptozotocin (STZ)-induced diabetes on acetaminophen metabolism and hepatotoxicity in male Sprague-Dawley (SD) and Long Evans Hooded (LEH) rats were compared. In agreement with earlier studies, normal SD rats were more resistant to acetaminophen-induced hepatic necrosis than normal LEH rats. In contrast to LEH rats, the diabetic state did not protect SD rats from liver injury. Pharmacokinetic studies revealed that normal SD rats eliminated acetaminophen faster than normal LEH rats, and that the diabetic state further enhanced elimination in both strains of rats; however, the effect was much greater in LEH rats. Normal SD rats had a greater capacity to metabolize acetaminophen to nontoxic glucuronide and sulfate conjugates than normal LEH rats. In LEH rats, the diabetic state enhanced acetaminophen glucuronidation and sulfation, whereas in SD rats the diabetic state increased only sulfation; glucuronidation was unaffected. Additional studies revealed that the difference in the glucuronidation capacities between normal LEH and normal SD rats was not due to differences in either the amount of the enzyme, glucuronyl transferase, or basal hepatic levels of the cofactor, UDPGA. Similarly, the diabetes-induced enhancement of glucuronidation in LEH rats was not due to differences in predrug levels of either glucuronyl transferase or UDPGA. Thus, the major difference in susceptibility of the two strains of normal rats to acetaminophen hepatotoxicity appears to be due to the capacity to clear the drug through nontoxic pathways. The greater glucuronidation capacity seen in diabetic LEH rats and in normal and diabetic SD rats as compared to normal LEH rats, appears to be due to a greater ability to produce UDPGA in response to the metabolic demand.
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PMID:Strain differences in susceptibility of normal and diabetic rats to acetaminophen hepatotoxicity. 308 Oct 10


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