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)

Collagen production has been shown to be decreased in costal cartilage from nondiabetic animals after incubation with diabetic rat serum. Since collagen was decreased to a similar degree in tissues from diabetic animals, we questioned whether altered collagen production in vivo could be related to altered production induced in vitro. Collagen and noncollagen protein production in articular cartilage from diabetic animals (production in vivo) was compared to protein production in dermal fibroblasts from non-diabetic rats exposed to serum from the same diabetic rats (production in vitro). Diabetes was induced by intravenous administration of 90 mg/kg of streptozotocin into male Sprague-Dawley rats. Cartilage was removed and incubated with [3H]-proline for 2 hours at 37 degrees C (in vivo), while fibroblasts were exposed to experimental serum from individual animals for 24 hours with addition of 5 microCi of [5-3H]-proline for the final 6 hours (in vitro). Collagen and noncollagen protein production were quantitated using purified bacterial collagenase. Collagen production in cartilage decreased to 46% (p less than .01) and noncollagen to 68% (p less than .05) of levels in control animals. Fibroblasts exposed to 2.5% diabetic serum decreased collagen and noncollagen protein production to levels of 30% (p less than .01) and 54% (p less than .05) of production in cells incubated in 2.5% normal rat serum. Correlation between defective collagen production in cartilage from individual rats and the effects of their own serum on collagen production in fibroblasts was significant (r = 0.84, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between decreased collagen production in diabetic animals and in cells exposed to diabetic serum: response to insulin. 160 33

5-Amino-4-imidazolecarboxamide (AICA) riboside, the nucleoside corresponding to AICA ribotide (AICAR or ZMP), an intermediate of the de novo pathway of purine biosynthesis, was found to exert a dose-dependent inhibition on gluconeogenesis in isolated rat hepatocytes. Production of glucose from lactate-pyruvate mixtures was half-maximally inhibited by approximately 100 microM and completely suppressed by 500 microM AICA riboside. AICA riboside also inhibited the production of glucose from all other gluconeogenic precursors investigated, i.e., fructose, dihydroxyacetone, and L-proline. Measurements of intermediates of the glycolytic-gluconeogenic pathway showed that AICA riboside provoked elevations of triose phosphates and fructose-1,6-bisphosphate and decreases in fructose-6-phosphate and glucose-6-phosphate. The effects of AICA riboside persisted when the cells were washed 10 min after its addition but were suppressed by 5-iodotubercidin, an inhibitor of adenosine kinase. AICA riboside provoked a dose-dependent buildup of normally undetectable Z nucleotides. After 20 min of incubation with 500 microM AICA riboside, ZMP, ZTP, and ZDP reached 3, 0.3, and 0.1 mumol/g cells, respectively. Concentrations of ATP were not significantly modified by addition of up to 500 microM AICA riboside when the cells were incubated with lactate-pyruvate but decreased with fructose or dihydroxyacetone. The activity of rat liver fructose-1,6-bisphosphatase was inhibited by ZMP with an apparent Ki of 370 microM. It is concluded that AICA riboside exerts a suppressive effect on gluconeogenesis because it provokes an accumulation of ZMP, which inhibits fructose-1,6-bisphosphatase.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Oct
PMID:Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes. 165 65

Osteopenia is a recognized complication of diabetes mellitus in humans and experimental animals. We recently found that tetracyclines prevent osteopenia in the streptozotocin-induced diabetic rat and that this effect was associated with a restoration of defective osteoblast morphology (Golub et al., 1990). The present study extends these initial ultrastructural observations by assessing osteoblast function in the untreated and tetracycline-treated diabetic rats. After a 3-week protocol, non-diabetic control and diabetic rats, including those orally administered a tetracycline, minocycline (MC), or a non-antimicrobial tetracycline analog (CMT), were perfusion-fixed with an aldehyde mixture; the humeri were dissected and processed for ultracytochemical localization of alkaline phosphatase (ALPase) and Ca-ATPase activities. Some rats from each experimental group received an intravenous injection of 3H-proline as a radioprecursor of procollagen, and the humeri were processed for light microscopic autoradiography. In addition, the osteoid volume in each experimental group was quantitatively examined by morphometric analysis of electron micrographs. During the diabetic state, active cuboidal osteoblasts in the endosteum of control rats were replaced by flattened bone-lining cells that contained few cytoplasmic organelles for protein synthesis (Golgi-RER system), and active transport (mitochondria). Treating diabetic rats with MC, and even more so with CMT, appeared to "restore" osteoblast structure. During diabetes, bone-lining cells incorporated little 3H-proline or secreted little labeled protein and produced only a very thin osteoid layer. Tetracycline administration to the diabetics increased both the incorporation of 3H-proline by osteoblasts and their secretion of labeled protein toward the osteoid matrix, in a pattern similar to that seen in the non-diabetic controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tetracycline administration restores osteoblast structure and function during experimental diabetes. 183 18

Human salivary proteins have been studied by electrophoresis in denaturing and non-denaturing polyacrylamide gel electrophoresis (PAGE) as well as by isoelectric focusing (IEF) and two-dimensional procedures, and the clinical applications of this have been reviewed. Whilst non-denaturing PAGE is useful in studying polymorphisms, sodium dodecylsulphate PAGE appears to be otherwise preferable. Immobilized pH gradients containing carrier ampholytes (CAs) give better resolution than CA-based IEF and overcome the problems of cathode drift and loss of basic material. Proline-rich proteins stain poorly with conventional procedures and special techniques are necessary. In clinical studies, findings must be viewed over and above the large number of polymorphisms which occur normally. Studies relating salivary protein and peptide profiles to dental caries susceptibility are encouraging. Specific protein abnormalities have been associated with connective tissue disorders and could form the basis of new non-invasive diagnostic procedures. Protein differences associated with cystic fibrosis and diabetes mellitus, however, merit reinvestigation with the new procedures now available. Detection of HIV antigens in saliva is a new area of research. In the light of new techniques available and new information which has arisen from DNA studies, future prospects for the clinical applications of electrophoresis of saliva look good.
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PMID:Clinical applications of electrophoresis of human salivary proteins. 193 89

Diabetes mellitus is associated with a generalized defect in connective tissue metabolism. Since collagen is the major protein of connective tissues, we used collagen as a probe to examine the role of factors in diabetic rat serum (DRS) in the etiology of these defects. Serum and skin fibroblasts were isolated from nondiabetic rats, and serum was taken from rats 48 h after injection of 200 mg/kg streptozotocin. Within 24 h of confluency, the fibroblast medium was changed to experimental serum for 24 h, with 5 microCi [3H]proline added for the final 6 h. Collagen and noncollagen proteins were quantitated using purified collagenase. Compared to cells incubated in medium without serum, collagen fell to 58% with 0.5% DRS (P less than 0.05) and continued to decrease with increasing concentrations of DRS. Noncollagen protein decreased below levels in cells incubated in medium without serum only when concentrations of diabetic serum were 1% or greater and did not decrease further with higher concentrations of diabetic serum. Collagen was decreased to a greater degree than noncollagen protein at each concentration of DRS, such that collagen relative to total protein production was significantly reduced at 0.5% or more DRS. Addition of 10(-7)-10(-9) M insulin or insulin-like growth factor-I (0.1-1000 ng/ml) to DRS did not return collagen production to the level seen in cells incubated in medium with no added serum (basal production). After separation of serum components based on size, incubation of cells with the low mol wt fraction (less than 5000 daltons) of normal and diabetic rat serum resulted in equivalent collagen production, while incubation with the high mol wt fraction of DRS resulted in 200-fold less collagen compared to the similar fraction of normal serum. This decrease in collagen production appeared due to the presence of a high mol wt factor(s) in diabetic serum which had a direct inhibitory effect on collagen and was not due to deficiency of growth peptides. The degree and specificity of these changes in collagen production probably contribute to long term complications in diabetes through altered connective tissue metabolism.
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PMID:Inhibition of collagen production by diabetic rat serum: response to insulin and insulin-like growth factor-I added in vitro. 195 85

Insulin-deficient, adult, diabetic rats were administrated a tetracycline (either minocycline or a chemically-modified non-antimicrobial tetracycline: CMT) by oral gavage over a 3-week period. Untreated diabetic and non-diabetic rats served as controls. On day 21, all rats received an intravenous injection of 3H-proline, as a radioprecursor of procollagen in bone, dentine and periodontal ligament (PDL) or of amelogenin in enamel; perfusion fixation with an aldehyde mixture was carried out at 20 minutes and 4 hours after isotope injection. The parietal bones (calvaria), mandibules including molars, and lower incisors of these rats were dissected and processed for light microscopic autoradiography to study 3H-proline utilization by osteoblasts, PDL fibroblasts, odontoblasts and ameloblasts. In the control rats, at 20 minutes after 3H-proline injection, silver grains of labeled precursor were detected in the osteoblasts of the periosteal surfaces of the parietal bones. At the 4 hour time period, although some radioprecursor was still present in the osteoblasts, most had progressed to the osteoid matrix. In contrast, the flattened bone-lining cells in the untreated diabetics showed minimal uptake and secretion of labeled proline at both time periods. In both minocycline- and CMT-treated diabetic rats, the labeled proline was localized in the osteoblasts and the osteoid in a pattern reminiscent of that seen in the control rats at both time periods. Of interest, CMT administration appeared to increase the labeling of the osteoid matrix more than minocycline treatment. In non-diabetic control rats, the PDL fibroblasts exhibited a polarized elongated profile and incorporated and secreted radioprecursor similar to that described for the osteoblasts in these animals. The PDL fibroblasts in the untreated diabetics lost their regular arrangement and incorporated little if any 3H-proline; once again, tetracycline administration appeared to normalize, at least in part, the structure and 3H-proline incorporation by these connective tissue cells. In contrast, diabetes and tetracycline administration did not affect the incorporation and secretion of radioprecursor by odontoblasts and secretory ameloblasts during tooth development.
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PMID:Insulin-deficient diabetes impairs osteoblast and periodontal ligament fibroblast metabolism but does not affect ameloblasts and odontoblasts: response to tetracycline(s) administration. 214 81

Islet amyloid polypeptide (IAPP), a putative polypeptide hormone, is a product of pancreatic beta-cells and the major constituent of the amyloid deposits seen mainly in islets of type 2 diabetic humans and diabetic cats. The connection between IAPP amyloid formation and diabetes is unknown, but a limited segment of the IAPP molecule, positions 20-29, seems responsible for the aggregation to fibrils. Differences in the amino acid sequence of this region probably determine whether or not islet amyloid can develop in a particular species. Amyloid fibril formation can be mimicked in vitro with the aid of synthetic peptides. With this technique we show that peptides corresponding to IAPP positions 20-29 of human and cat, species that develop IAPP-derived islet amyloid, form amyloid-like fibrils in vitro. The corresponding IAPP segment from three rodent species that do not develop IAPP-derived amyloid did not give rise to fibrils. Substitution of the human IAPP-(20-29) decapeptide with one or two amino acid residues from species without islet amyloid generally reduced the capacity to form fibrils. We conclude that the sequence Ala-Ile-Leu-Ser-Ser, corresponding to positions 25-29 of human IAPP, is strongly amyloidogenic and that a proline-for-serine substitution in position 28, as in several rodents, almost completely inhibits formation of amyloid fibrils.
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PMID:Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formation. 219 44

Accumulation of brown products in long-lived proteins might be an important factor in determining long-term diabetic complications. Fluorescent chromophore 2-(2-furoyl)-4-(5)-(2-furanyl)-1H-imidazole (FFI), isolated from hydrolyzed brown products synthesized in vitro, was proposed as a specific brown product responsible for functional and structural changes in long-lived proteins. In this study, an attempt was made to demonstrate by means of collision spectroscopy the presence of FFI in collagen samples taken from diabetic rats. Diabetic rat collagen samples showed mean values of absorbance per milligram of 4-hydroxy-L-proline significantly higher than those observed in nondiabetic rats, suggesting higher FFI levels. Surprisingly, all collagen samples from diabetic and nondiabetic rats gave collision spectra in which no peak diagnostic of FFI presence was observed. These data suggest that the absorbance level observed in diabetic rats is not due to the presence of FFI but to structurally related compounds, which are being investigated by means of mass spectrometry.
Diabetes 1990 Jan
PMID:Absence of brown product FFI in nondiabetic and diabetic rat collagen. 221 60

Streptozotocin (STZ)-induced diabetes depresses the rate of vascular collagen synthesis in the spontaneously hypertensive rat (SHR), but it also reduces arterial pressure (SAP) in this strain. We investigated this phenomenon further by comparing the SHR with the renovascular hypertensive (RVH) rat, because diabetes does not affect SAP in the latter model of hypertension. Renovascular hypertension was induced by clipping the left renal artery of Wistar-Kyoto (WKY) rats; sham-operated WKY were included as normotensive controls. Collagen synthesis of arterial tissue in vitro was quantified as prolyl hydroxylase activity and the rate of radioactive proline incorporation into collagen. Arterial collagen synthesis of nondiabetic SHR and RVH animals was elevated compared to that of the nonhypertensive WKY controls. STZ-induced diabetes (8 weeks) reduced SAP of SHR, but had no effect on SAP of either RVH or normotensive WKY rats. However, diabetes significantly depressed vascular collagen synthesis of both SHR and RVH rats, and, less consistently, of the WKY. The results strongly suggest that STZ-induced diabetes in SHR impairs arterial collagen synthesis independent of associated changes in arterial pressure.
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PMID:STZ-induced diabetes in SHR and renovascular hypertensive rats: dissociation between changes in arterial pressure and vascular collagen synthesis. 224 11

This study measured the velocity of fast orthograde axonal transport of incorporated 3H-proline in motoneurones of the sciatic nerve in control rats and in rats with streptozotocin-induced diabetes of 3 weeks duration. Sciatic nerve and abdominal cavity temperatures were monitored throughout the period of measurement of transport velocity, and the rats were warmed to minimise hypothermia at both sites. There was marked abdominal and sciatic nerve hypothermia immediately after operation, and this effect was more intense in diabetic rats than in control rats. In steady state, abdominal cavity temperature (mean +/- SEM) was 38.1 +/- 0.1 degree C in both control and diabetic rats, and the sciatic nerve temperatures were 37.8 +/- 0.1 degree C in controls and 37.1 +/- 0.3 degrees C in diabetic rats. The difference was not statistically significant. The velocities of orthograde axonal transport for the fastest molecules containing 3H-proline were 14.0 +/- 0.9 (SEM)mm/h for controls and 13.9 +/- 1.1 (SEM)mm/h for diabetic rats. Thus, no velocity difference was observed. The findings are discussed in relation to measurements of fast orthograde transport velocity in experimental diabetes in other studies. It is suggested that, where velocity deficits have been seen in diabetic rats, nerve hypothermia should be considered as a contributory factor.
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PMID:Fast orthograde axonal transport in sciatic motoneurones and nerve temperature in streptozotocin-diabetic rats. 241 4


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