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)

Tight junctional fibrils were absent in freeze-fracture replicas of rat and human islets in situ, but were easily discerned in collagenase-isolated islets. Disruption of the pancreatic gland and its exposure to trypsin were each found to induce tight junction formation in rat islets. The amount of tight junctions between islet cells declined progressively during culture, but tight junctional structures remained detectable after 1 day of culture. It is suggested that rather than being involved in normal islet cell function tight junctions provide an adaptive mechanism intended to seal and hence to protect islet microdomains against sudden perturbations in local interstitial fluid.
Diabetes 1984 Jan
PMID:Evidence against the presence of tight junctions in normal endocrine pancreas. 636 Jul 63

The effect of insulin on glucose transport (2-deoxyglucose uptake) in adipocytes was measured in the absence and in the presence of 10 mM sodium-DL-beta-hydroxybutyrate. The ketone body had little or no effect on the basal or the maximally insulin-stimulated rate of transport. However, beta-hydroxybutyrate potentiated the effect of submaximal concentrations of insulin, i.e., it resulted in a leftward shift in the dose-response curve. The half-maximally effective concentration of insulin was decreased by approximately 30% from 0.58 ng/ml to 0.40 ng/ml. beta-Hydroxybutyrate caused a slight (approximately 10%) increase in 125I-insulin binding to the cells. To determine whether this small increase in insulin binding is responsible for the increased insulin sensitivity in the presence of the ketone, two mimickers of insulin action were used: a serum containing anti-insulin receptor antibodies and hydrogen peroxide. beta-Hydroxybutyrate increased the sensitivity of glucose transport to stimulation by the anti-receptor antibody, demonstrating that insulin itself does not have to be present. beta-Hydroxybutyrate also potentiated the effect of hydrogen peroxide (which acts at a level distal to the insulin receptor) even in cells that had been depleted of insulin receptors by trypsin treatment. Therefore, beta-hydroxybutyrate acts, at least partly, at a post-insulin receptor level. Adenosine increases the insulin sensitivity of adipocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 Nov
PMID:beta-Hydroxybutyrate increases the insulin sensitivity of adipocyte glucose transport at a postreceptor level. 638 23

The native or modified alpha-amylase inhibitor Hoe 467A - isolated from the culture medium of Streptomyces tendae 4158 - and overlapping peptides were degraded by the automatic Edman technique. The oxidized or aminoethylated or oxidized and maleoylated inhibitor was digested with trypsin and the native inhibitor with pepsin. Further digestion with Staphylococcus aureus proteinase was also carried out. After peptic digestion two cystin peptides were isolated, which allowed the establishment of the disulfide bonds. The alpha-amylase inhibitor is a polypeptid consisting of 74 amino-acid residues with a molecular mass of 7958 Da. The inhibitor is composed of all naturally occurring amino acids except methionine and phenylalanine and shows no sequence homology to known inhibitors. The clinical and pharmacological importance in respect to the inhibitors ability for inactivation of human salivary and pancreatic alpha-amylase is discussed. Especially the proteinase resistance of the inhibitor enables a clinical application in human (e.g. Diabetes mellitus) per os.
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PMID:[The primary structure of the alpha-amylase inhibitor Hoe 467A from Streptomyces tendae 4158. A new class of inhibitors]. 660 9

Exocrine pancreatic function was evaluated in 19 diabetic children on the basis of a pancreozymin-secretin test, a p-aminobenzoic acid (PABA) test, and a determination of fasting plasma trypsin and elastase-1 levels. In the pancreozymin-secretin test, the diabetics exhibited lower mean values in all the parameters measured, significant differences being seen in the volume of duodenal fluid and the output of bicarbonate and amylase. Compared to the controls, the diabetics also had lower levels in the PABA test and in the trypsin and elastase-1 measurements. No significant correlation was seen between exocrine pancreatic dysfunction and the duration of diabetes. However, the duration of diabetes in children who showed extremely low levels (below the mean +/- 2 SD for the control subjects) in the PABA test and low plasma trypsin and elastase-1 values was more than 1 year. This study revealed that diabetic children had reduced exocrine pancreatic function, some in an early stage of the disease. Therefore, the reduction may be due to a functional disturbance rather than to an anatomical loss of exocrine pancreatic tissue.
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PMID:Exocrine pancreatic function in diabetic children. 661 Jul 39

The BB rat spontaneously develops a diabetic state that closely resembles human type I diabetes. The authors studied the pathologic changes of the retina and retinal pigment epithelium of four normal and nine diabetic BB rats using (1) light and electron microscopy with the horseradish peroxidase tracer technique, and (2) trypsin digest preparations of the retinal vessels. They observed a retinal pigment epitheliopathy characterized by (1) derangement of the plasmalemma infoldings; (2) patchy organelle degeneration leading to focal necrosis; (3) increased permeability to horseradish peroxidase; and (4) repair of the pigment epithelium. Focal thickening of the retinal vascular basement membrane was seen occasionally, but the trypsin digest preparations were unremarkable. These studies suggest that diabetic retinal pigment epitheliopathy may be one of the early changes of diabetic retinopathy and may provide a pathogenetic mechanism for early disruption of the blood-retinal barrier.
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PMID:Pathologic studies of the blood--retinal barrier in the spontaneously diabetic BB rat. 669 48

An investigation of serum immunoreactive trypsin concentration and pancreatic isoamylase activity in patients with diabetes mellitus has shown that exocrine pancreatic deficit is maximal in insulin dependent diabetics, intermediate in those controlled with sulphonylureas, and absent in patients controlled with biguanides or diet or both. A significant correlation between the serum concentrations of both these pancreatic enzymes and C peptide was found. Serum pancreatic enzyme concentrations were not related to glycosylated haemoglobin concentrations, the dosage of insulin, or the age of onset of diabetes. The concentration of immunoreactive trypsin was found to be low in most of the insulin dependent diabetics in whom this enzyme was measured at the time of the clinical onset of diabetes. Thus exocrine pancreatic deficit in diabetes closely parallels the endocrine beta cell deficit and occurs concurrently with, or antedates, the clinical presentation of type I diabetes. It is therefore possible that in type I diabetes similar mechanisms are entailed in the pathogenesis of impaired endocrine and exocrine pancreatic function.
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PMID:Exocrine pancreatic function in diabetes mellitus. 669 93

Immunoreactive trypsin (IRT) and pancreatic lipase were measured in serum from 37 geriatric in-patients (median age 77.5 years) without history of diarrhoea, pancreatic disease, diabetes or acute or chronic alcoholic intake. IRT and pancreatic lipase concentrations/activity were strongly correlated and were markedly elevated when compared with a control population of 22 subjects (median age 27 years). Such elevations in pancreatic enzymes indicate a subclinical damage of exocrine pancreatic tissue. Assessment of exocrine pancreatic function in the geriatric age group should not be based on pancreatic enzyme levels in serum.
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PMID:Serum pancreatic enzymes in the elderly. 671 39

We have previously shown that increased nonenzymatic glycosylation occurs in peripheral nervous tissue of diabetic humans and animals, primarily on the PO-protein of peripheral nerve myelin. The pathophysiologic mechanism by which this biochemical alteration leads to myelin breakdown and removal is not as yet understood. In the present study we show that advanced glycosylation end-product (AGE) adducts that form during long-term exposure of peripheral nerve myelin proteins to glucose in vitro and in vivo markedly alter the way in which myelin interacts with elicited macrophages. In this interaction, macrophages appear to specifically recognize AGEs on myelin, since AGE-BSA competes nearly as effectively as AGE-myelin, while neither unmodified BSA nor unmodified myelin compete. The failure of yeast mannan to interfere with macrophage recognition of AGE-myelin suggests that the mannose/fucose receptor does not mediate this process. Recognition of AGE-protein by macrophages is associated with endocytosis, as demonstrated by resistance of cell-associated radioactivity to removal by trypsin action, and by low temperature inhibition of ligand accumulation in the cellular fraction. 125I-labeled myelin that had been incubated in vitro with 50 mM glucose for 8 wk reached a steady state accumulation within thioglycolate-elicited macrophages that was five times greater than that of myelin incubated without glucose. Similarly, myelin isolated from rats having diabetes for 1.5-2.0 years duration had a steady state level that was 9 times greater than that of myelin from young rats, and 3.5 times greater than that of myelin from age-matched controls. In contrast, myelin isolated from rats having diabetes for 4-5 wk had the same degree of accumulation observed with myelin of age-matched normal rats. These data suggest that the amount of increased nonenzymatic glycosylation observed in the myelin of short-term diabetic rats had not yet resulted in the significant accumulation of AGE-myelin present both in vitro and in the long-term diabetic rats. The disappearance of acid-insoluble radioactivity from within the cells and the appearance of acid-soluble radioactivity released into the medium were very similar for the two groups, suggesting that the striking difference in accumulation seen between normal myelin and AGE-myelin is due primarily to increased uptake. Formation of irreversible AGE-adducts on myelin appears to promote the recognition and uptake of the modified myelin by macrophages. This interaction between AGE-myelin and macrophages may initiate or contribute to the segmental demyelination associated with diabetes and the normal aging of peripheral nerve.
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PMID:Accumulation of diabetic rat peripheral nerve myelin by macrophages increases with the presence of advanced glycosylation endproducts. 673 70

Evidence from a number of laboratories has suggested that the mechanism of insulin action involves the release of an intracellular mediator polypeptide from the plasma membrane. It has been proposed that activation of a protease with trypsin-like specificity is involved in release of the putative mediator. In an effort to assess the potential role of such a protease in intact cells, the present study tested the effects of a variety of low-mol-wt protease inhibitors on insulin's metabolic action in isolated rat epididymal fat cells. The protease inhibitors studied included p-aminobenzamidine, benzamidine, phenylguanidine, diisopropylfluorophosphate, leupeptin, and the competitive substrate N-alpha-tosyl-L-arginine methylester. Leupeptin was devoid of activity. Most of the other inhibitors used were able to interfere with insulin-stimulated metabolism if used in sufficiently high concentrations, concentrations considerably higher than those required for inhibition of known proteases or inhibition of intracellular processes in a previously described system which involves a trypsin-like enzyme. Moreover, they displayed various activities unrelated to protease inhibition that could explain their effects on insulin action better than protease inhibition. While none of the data on individual inhibitors were by themselves convincing enough to either confirm or reject the hypothesis concerning the involvement of a protease with trypsin-like specificity in insulin action, taken together our results do weaken the hypothesis considerably and in particular render the involvement of an extracellular trypsin-like enzyme improbable.
Diabetes 1982 Nov
PMID:On the mechanisms of inhibition of insulin action by small-molecular-weight trypsin inhibitors. 675 16

The course of alloxan diabetes in rats in different methods of isotransplantation of the islets of Langerhans isolated by means of trypsin, versen, and collagenase was studied. The transplanted islets can compensate insulin deficiency in rats with experimental diabetes. The period of normoglycemia depended on the number of the transplanted islets and the sites of their introduction. In intraperitoneal and intramuscular (m. rectus abdominis) methods of the islet tissue implantation normoglycemia was observed from 1.5 to 3.5 months, and in intrahepatic method it persisted from 4 to 10 months. The advantage of intrahepatic transplantation of the islets of Langerhans was shown.
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PMID:[Characteristics of the course of alloxan diabetes in rats with various methods of isografting the islands of Langerhans]. 676 33


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