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

There is a marked difference in insulin secretion between the ob+/ob+ obese mouse and its non-obese littermate. Numerous peptides have been implicated in the modification of postprandial insulin secretion. In this study, the morphological and immunohistochemical studies of the genetically obese mouse (ob+/ob+) pancreata were compared with control littermates. Additionally, the distribution of gastric inhibitory polypeptide, somatostatin, glucagon, and insulin immunoreactive cells was also quantitated. Hyperglycemia and hyperinsulinemia were verified in the obese mice. The control animals had some islets and ductules with mononuclear infiltrations of a possible immune character. The obese individuals had a marked increase in both number and size of the islets of Langerhans compared with lean controls. The insulin immunocytochemical reaction in the obese pancreatic beta-cells was weaker than that of controls, as was the aldehyde-fuchsin reaction. The glucagon, gastric inhibitory polypeptide, and somatostatin containing cells were intermingled with the beta-cells. In contrast, the control animals showed a peripheral localization of these cell types. The morphometric analysis of the obese pancreas showed a decreased proportion of non-beta cells within the islets but not in total pancreatic volume in comparison with controls. The obese mouse also had cavities filled with eosin-stained material among numerous beta-cells. No complete epithelial lining distinguished these formations from the surrounding islet cells. The content of the cavities was not stained by any of the immunocytochemical reactions applied. In conclusion, the pancreatic islets of the ob+/ob+ mouse show marked differences in both morphological and immunocytochemical characteristics if compared with control littermates. These differences in architecture may be related to the eventual development of diabetes mellitus in the ob+/ob+ mouse.
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PMID:A morphological and immunohistochemical investigation of endocrine pancreata from obese ob+/ob+ mice. 167 42

It has been previously demonstrated that non-enzymatic glycosylation and subsequent cross-linking of proteins can occur at high or greater than physiological concentrations of glucose. Soluble collagen was incubated in the presence of increasing glucose concentrations. The amount of cross-linked collagen was determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Our findings reveal that cross-linking due to non-enzymatic glycosylation occurs at or near physiological concentrations of glucose (3.11-4.22 mM). In addition, this glucose induced cross-linking is a time dependent reaction. When collagen was incubated with a variety of different carbohydrates it was found that ketoses are more active cross-linking agents than aldoses. The addition of a reactive group (such as an amine) alpha to the aldehyde group on the carbohydrate increases the cross-linking activity of glucose 2.8 fold. Blockage of the reactive group alpha to the aldehyde (such as N-acetyl glucosamine or 2-deoxy-D-glucose) totally abolishes glycosylation activity. Both 5-C and 7-C carbohydrates are more active than 6-C carbohydrates. Thus, although glucose may be the most abundant carbohydrate capable of non-enzymatic glycosylation and subsequent cross-linking, it is not the most chemically reactive. However, the significance of these findings to the pathogenesis of diabetes needs to be defined.
Diabetes Res 1991 Jan
PMID:Effect of carbohydrate structure and concentration on the non-enzymatic glycosylation and subsequent cross-linking of collagen. 181 96

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

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

Aldehyde reductase [EC 1.1.1.2] and aldose reductase [EC 1.1.1.21] are monomeric NADPH-dependent oxidoreductases having wide substrate specificities for carbonyl compounds. These enzymes are implicated in the development of diabetic complications by catalyzing the reduction of glucose to sorbitol. Enzyme inhibition as a direct pharmacokinetic approach to the prevention of diabetic complications resulting from the hyperglycemia of diabetes has not been effective because of nonspecificity of the inhibitors and some appreciable side effects. To understand the structural and evolutionary relationship of these enzymes, we cloned and sequenced cDNAs coding for aldose and aldehyde reductases from human liver and placental cDNA libraries. Human placental aldose reductase (open reading frame of 316 amino acids) has a 65% identity (identical plus conservative substitutions) to human liver and placental aldehyde reductase (open reading frame of 325 amino acids). The two sequences have significant identity to 2,5-diketogluconic acid reductase from corynebacterium, frog rho-crystallin, and bovine lung prostaglandin F synthase (reductase). Southern hybridization analysis of human genomic DNA indicates a multigene system for aldose reductase, suggesting the existence of additional proteins. Thus, the aldo-keto reductase superfamily of proteins may have a more significant and hitherto not fully appreciated role in general cellular metabolism.
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PMID:The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases. 249 33

The combined effects of cyclosporin (CYA) and prednisolone (PSL) on the function and morphology of pancreatic B cells of Wistar rats were investigated. Four 13-day treatment groups were compared; these were the O group (olive oil alone, p.o.), the P group (PSL 3 mg/kg/day, i.m.), the C group (CYA 20 mg/kg/day, p.o.), and the PC group (PSL 3 mg/kg/day, i.m. plus CYA 20 mg/kg/day, p.o.). Glucose tolerance was equally impaired in the C and PC groups. The pancreatic insulin content in the C group was 49.7% of that of the O group, whereas that in the PC group was 81.1%. Morphometric analysis using modified aldehyde-fuchsin staining revealed that 'percent beta-granule area' in the islet was 17.5%, 15.0%, 6.5%, and 7.8% in the O, P, C, and PC groups, respectively. Ultrastructurally, pancreatic B cells in the PC group showed CYA damage; however, a significant number of B cells exhibited hypertrophy of the rough endoplasmic reticulum and the Golgi apparatus, suggesting concomitant B cell hyperactivity in this group. These findings suggest that PSL does not aggravate the toxic effects of CYA on pancreatic B cells during short-term treatment; rather, it might be protective.
Diabetes Res Clin Pract 1989 Apr 01
PMID:The effect of prednisolone on cyclosporin-induced damage of pancreatic B cells in Wistar rats. 265 67

The paper is devoted to a study of the role of serum glycoprotein fructosamine and serum albumin in the pathogenesis of a severe course of insulin dependent diabetes mellitus (IDDM) in children. Fructosamine was determined in 43 pediatric patients with IDDM by direct spectrophotometry using Hoffman-La-Roche kits; albumin, C-peptide and malonic aldehyde were also determined. Disorder of the mechanism of regulation of homeostasis by albumin was shown to play an important role in the pathogenesis of a severe course of IDDM in children. It could be caused by its enhanced glycosylation and a decrease in liver synthesis in some cases as a result of considerable reduction of insulin secretion. A prognostically unfavorable sign was a raised ratio of fructosamine to albumin and enhanced lipid peroxidation against a background of low insulin secretion. The determination of serum levels of fructosamine and albumin can be a valuable diagnostic criterion in examination of children with diabetes mellitus.
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PMID:[Clinical significance of the determination of serum fructosamine and albumin in children with diabetes mellitus]. 271 69

Since evidence suggests that ascorbic acid deficits may provoke certain diabetic complications, it becomes necessary to develop a diabetic animal model which, like man, is unable to synthesize this vitamin. To this end, the present study monitored the diabetogenic effects of streptozotocin (STZ, 150 mg/kg) in the male guinea pig, a species rarely used in diabetes research. Over a 3-week period, body weight and relative food intake were lower in the STZ group compared to controls. The mean daily water intake and urine volume of the STZ group after 1 week were 175 and 270% of their initial pretreatment values, respectively, while control values were unchanged. The STZ group also exhibited a persistent glycosuria throughout the study. At the end of 3 weeks, aldehyde fuchsin staining of pancreatic beta cell granules (an index of stored insulin) was 58% lower in the STZ group compared to controls. Plasma C-peptide (indicator of insulin secretion) was expressed in human equivalents (mean +/- SEM). C-peptide was reduced in the STZ group (103 +/- 65 pg/ml) compared to controls (549 +/- 96 pg/ml); however, no change in plasma glucose was observed. Plasma ascorbic acid levels also were lower for STZ animals (150 +/- 26 micrograms%) versus controls (410 +/- 28 micrograms%). This study 1) demonstrates a diabetic syndrome in the STZ-treated guinea pig based on a reduced growth rate, beta cell dysfunction, polydipsia, polyuria and glycosuria, and 2) suggests the usefulness of this diabetic model in studies of pathologic mechanisms influenced by ascorbic acid.
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PMID:Selected physical and biochemical parameters in the streptozotocin-treated guinea pig: insights into the diabetic guinea pig model. 295 57

Human platelet membrane proteins (PMP), incubated in vitro in the presence of various concentrations of glucose, undergo nonenzymatic glycation, as evidenced by incorporation of [3-3H]glucose radioactivity into the acid-precipitable fraction. The time course of the reaction is linear for the first hours, and the rate of glycation depends on the glucose concentration in the medium: at a glucose concentration of 80 mmol/L, up to 60 nmol of glucose is bound per milligram of PMP. The ketoaminic nature of the glucose/protein linkages was demonstrated by the finding of 5-hydroxymethylfurfuraldehyde by liquid-chromatographic analysis of acid hydrolysates of PMP. We analyzed PMP from 13 subjects with type I poorly controlled diabetes and from 10 nondiabetics. Nonenzymatic glycation, evaluated as nanomoles of the aldehyde per milligram of protein, was much greater in diabetic patients than in nondiabetics: 1.58 +/- 0.70 vs 0.37 +/- 0.18 (mean +/- SD).
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PMID:Nonenzymatic glycation of human platelet membrane proteins in vitro and in vivo. 371 41

The stabilities of 14C-acetaldehyde with various hemoglobin fractions (HbA1a + b, HbA1a, and HbA0) were examined by determining amounts of adducts remaining after dialysis at 4 degrees C for various time intervals. Significant differences were found in the stabilities of adducts formed with various hemoglobin fractions. Acetaldehyde adducts formed with HbA1a + b were more stable to dialysis than adducts formed with HbA0 or HbA1c (7-8% of total adducts formed with HbA1a + b were stable to dialysis, compared with 4-5% stable adducts formed with either HbA0 or HbA1c). While only 37-57% of the trichloroacetic acid (TCA) precipitable adducts from HbA0 or HbA1c samples were stable to dialysis, 72-75% of TCA precipitable adducts from HbA1a + b were retained after dialysis. Posttranslational modification of hemoglobin by phosphorylated glycolytic intermediates appears to alter the physical properties of hemoglobin following further modification with acetaldehyde. In view of the increased amounts of glycosylated proteins found in patients with diabetes, these observations may be relevant to the pathogenesis of the sequelae of diabetes and/or alcoholism and the influence of one chronic illness on the other.
Diabetes Res 1986 Jun
PMID:Stability of acetaldehyde fractions with various hemoglobin fractions. 374 46


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