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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study investigated the effect of polymerization shrinkage of posterior composite (Herculite) on the dimensions and fracture strength of human maxillary premolars with a phosphonate-ester DBA (Bondlite) and a second DBA comprised of 4-META with MMA/TBB (Superbond). The individual role of etched enamel and nonetched dentin bonding was also studied with high-copper amalgam used as a control. Two sizes of preparation isthmus were designated for evaluation of the effect of the polymerization contraction on weakened teeth. The following conclusions were drawn. 1. Narrow intracoronal tooth preparations were significantly stronger than wider, expansive preparations. There was no difference among the narrow isthmus preparations restored with amalgam or acid etching and composite. 2. There was a significant expansion in tooth dimension when MOD cavities were restored with amalgam. 3. Teeth with narrow isthmus preparations using composite bonded with Bondlite adhesive to etched enamel demonstrated a significant contraction compared with Superbond DBA. 4. Composite restorations using Superbond DBA in wide MOD cavities significantly improved the fracture strength of maxillary premolars. 5. Superbond DBA with composite restorations benefited the tooth in dimensional change and fracture strength. 6. There was a positive correlation between the fracture strength and tooth dimension.
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PMID:Cuspal deformation and fracture resistance of teeth with dentin adhesives and composites. 305 37

The aim of this in vitro trial was to evaluate the external and internal adaptation of class II composite restorations to tooth structure by means of replica scanning electron microscope (SEM) observation. Standard MOD preparations were cut in human extracted teeth with margins located above and below the cementoenamel junction. Cavities were restored with either a direct multilayered technique, inlays (using conventional or dual DBA application) or prepolymerized composite inserts, using similar restorative material (Syntac, Variolink and Tetric). Evaluations were performed after mechanical and thermocycling. For the marginal adaptation in enamel, the bevelled margins of the direct group resulted in higher percentages of "continuity" (92.5% mesially and 94.6% distally), while the "marginal tooth fracture" was the most commonly found defect in groups with a butt preparation (up to 29.4%, with inserts). For the marginal adaptation in dentin, "continuity" percentages varied from 59% (inlay) to 87.9% (insert). As regards the internal adaptation, results for the whole dentin interface varied from 43.1% (inlay) to 63.9% (inlay with dual bonding) of "continuity". No regional difference in internal adaptation was found between the different preparation areas, except between gingival dentin and gingival enamel (44.9% vs. 80.7% of continuity, all group pooled data). Debonding occurred only at the dentin-restoration interface and consistently took place at the top of the hybrid layer. In the present experimental conditions, the inlay or insert techniques, which make use of the Dual bonding concept, proved to have the best potential to maintain the integrity of dentin-restoration interface.
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PMID:In vitro evaluation of marginal and internal adaptation of class II resin composite restorations after thermal and occlusal stressing. 987 16

Type 2 diabetes is characterized by a susceptibility to beta-cell failure. However, subjects at risk of developing type 2 diabetes, such as those with obesity or a family history of diabetes, have been shown to display hyperinsulinemia. Although this hyperinsulinemia may be an adaptive response to insulin resistance, the possibility that insulin hypersecretion may be a primary defect has not been thoroughly investigated. The DBA/2 mouse is a model of pancreatic islet susceptibility. Unlike the resistant C57BL/6 mouse strain, the DBA/2 mouse islet fails when stressed with insulin resistance or when exposed to chronic high glucose concentrations. The aim of this study was to compare insulin secretory function in the DBA/2 and C57BL/6 strains in the absence of insulin resistance or high glucose. Insulin secretion was assessed in vivo using the iv glucose tolerance test and in vitro using isolated islets in static incubations. It was shown that DBA/2 mice hypersecreted insulin in vivo, compared with C57BL/6 mice, at 1 d and at 4 and 10 wk of age. This hypersecretion was not attributable to insulin resistance (as assessed by the insulin tolerance test) or increased parasympathetic nervous system outflow. Insulin hypersecretion was also demonstrated in vitro. This was associated with higher glycolysis and glucose oxidation, and elevated activity (but not protein levels) of islet glucokinase and hexokinase. Furthermore, GLUT2 protein levels were higher, which may explain an increase in glucokinase activity in DBA/2 mouse islets. In summary, the DBA/2 mouse, a model of islet failure, has increased glucose-mediated insulin secretion from a very early age, which is associated with an increase in glucose utilization. Further studies will determine whether there is a link between insulin hypersecretion and subsequent beta-cell failure.
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PMID:Comparison of insulin secretory function in two mouse models with different susceptibility to beta-cell failure. 1202 Nov 73

Type 2 diabetes is a complex disease in which genetic and environmental factors interact to produce alterations in insulin action and insulin secretion, leading to hyperglycemia. To evaluate the influence of genetic background on development of diabetes in a genetically susceptible host, we generated mice that are double heterozygous (DH) for knockout of the insulin receptor and insulin receptor substrate-1 on three genetic backgrounds (C57BL/6 [B6], 129Sv, and DBA). Although DH mice on all backgrounds showed insulin resistance, their phenotypes were dramatically different. B6 DH mice exhibited marked hyperinsulinemia and massive islet hyperplasia and developed early hyperglycemia, with 85% overtly diabetic by 6 months. By contrast, 129Sv DH mice showed mild hyperinsulinemia and minimal islet hyperplasia, and < 2% developed diabetes. DBA mice had slower development of hyperglycemia, intermediate insulin levels, and evidence of islet degeneration, with 64% developing diabetes. Thus, mice carrying the same genetic defects on different backgrounds exhibited the full spectrum of abnormalities observed in humans with type 2 diabetes, which allowed for identification of potential loci that promote development of the diabetic phenotype.
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PMID:Impact of genetic background on development of hyperinsulinemia and diabetes in insulin receptor/insulin receptor substrate-1 double heterozygous mice. 1276 66

To identify new genetic determinants relevant to type 2 diabetes (T2D), diabetic F2 progeny were generated by intercrossing F1 mice obtained from a cross of BKS.Cg-Lepr(db)+/+m and DBA/2, and T2D-related phenotypes were measured. In the F2 population, increased susceptibility to diabetes and obesity was observed. We also detected the major quantitative trait loci (QTL) modifying the severity of diabetes on chromosome 9, where peaks of logarithm of odds (LOD) overlapped for three traits. To identify candidate genes in the QTL intervals, we combined "expression QTL" (eQTL), taking mRNA levels as quantitative traits, and "interstrain sequence variations, including cSNPs." As a result, four genes were identified from cosegregation of clinical QTL with eQTL and 13 genes were found from interstrain cSNPs as candidates in the T2D modifier QTL. Our combined approach shows the acceleration of the discovery of candidate genes in the QTL of interest, spanning several megabases.
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PMID:Identification of candidate genes in the type 2 diabetes modifier locus using expression QTL. 1582 Mar 11

Most quantitative trait loci (QTL) studies have focused on detecting the genetic effects of individual QTLs. This study thoroughly dissected the genetic components of type 2 diabetic mice, including a search for epistatic interactions and multi-locus additive effects that result in variation in diabetes-related phenotypes. F2 population was generated from BKS.Cg-Leprdb+/+m and DBA/2 intercross and separated into six subpopulations by sex and the db-dependent diabetes severity. Single-locus and pairwise genome scans first identified the QTLs in these F2 subpopulations, and next covariate-dependent scans confirmed their sex-, db- and sex-by-db-specific effects in the combined populations. Single-locus genome scans detected four QTLs (QBIS1, QBIS2, QBIS3 and QBIS4) that presented their genetic effects beyond sex, but most QTLs showed their effects specifically in limited conditions. This highly conditional feature of the QTLs was accentuated in the pairwise analysis. The pairwise genome scans uncovered a total of 27 significantly interacting or additively acting pairs of loci, showing a better fit to explain the total phenotypic variation of the traits. These significant pairs affected the traits under constantly varying combinations of loci in a time series or in both sexes. In addition, pairwise analysis indicated the appropriate genetic background in constructing congenic strains to obtain the maximum power in the replication of phenotypes. Our study showed high degree of complexity in the genetics of type 2 diabetes in mice, and it suggested that a comprehensive understanding of the multi-locus effects was essential to disentangle the complex genetics of diabetes and obesity in humans.
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PMID:Multidimensional genome scans identify the combinations of genetic loci linked to diabetes-related phenotypes in mice. 1632 90

Perinatal growth restriction (PGR) is associated with type 2 diabetes and hypertension. Identification of an isogenic mouse model of fetal programming will facilitate mechanistic understanding. We sought to test the hypotheses that 1) PGR impairs glucose tolerance and induces hypertension; and 2) the programming phenotype is more severe in an inbred mouse strain susceptible to diabetes (C57BL/6) than in a strain without such genetic predisposition (DBA/2). PGR pups were paired at weaning with same sex normally grown littermates. Glucose and insulin tolerance tests were performed at 17 wk, and systolic blood pressure (SBP) was measured at 20 wk. Impaired glucose tolerance was evident only among female PGR mice from both strains. While PGR did not alter insulin sensitivity in either strain, female DBA/2 mice had significantly decreased insulin levels during glucose tolerance testing. SBP was increased in PGR male C57BL/6 mice (p<0.01), while heart rate was decreased in PGR male DBA/2 mice (p<0.05). These studies indicate that in isogenic mice, PGR alters endocrine and cardiovascular physiology in female and male mice, respectively. Strain-and sex-specific genetic susceptibilities emphasize the need to consider genetic predisposition when evaluating the role of the perinatal environmental in the inception of adult disease.
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PMID:Naturally occurring perinatal growth restriction in mice programs cardiovascular and endocrine function in a sex- and strain-dependent manner. 1766 47

When the homozygous active form of porcine TGF-beta1 transgene (Tgf/Tgf) (under control of the rat glucagon promoter) is introduced into the nonobese diabetic mouse (NOD) genetic background, the mice develop endocrine and exocrine pancreatic hypoplasia, low serum insulin concentrations, and impaired glucose tolerance. To identify genetic modifiers of the diabetic phenotypes, we crossed hemizygous NOD-Tgf with DBA/2J mice (D2) or C3H/HeJ mice (C3H) and used the "transgenic mice" for quantitative trait loci (QTL) analysis. Genome-wide scans of F(2)-D Tgf/Tgf (D2 x NOD) and F(2)-C Tgf/Tgf (C3H x NOD), homozygous for the TGF-beta1 transgene, identified six statistically significant modifier QTLs: one QTL (Tdn1) in F(2)-D Tgf/Tgf, and five QTLs (Tcn1 to Tcn5) in F(2)-C Tgf/Tgf. Tdn1 (Chr 13, LOD = 4.39), and Tcn3 (Chr 2, LOD = 4.94) showed linkage to body weight at 8 weeks of age. Tcn2 (Chr 7, LOD = 4.38) and Tcn4 (Chr 14, LOD = 3.99 and 3.78) showed linkage to blood glucose (BG) concentrations in ipGTT at 30, 0, and 120 min, respectively. Tcn1 (Chr 1, LOD = 4.41) and Tcn5 (Chr 18, LOD = 4.99) showed linkage to serum insulin concentrations in ipGTT at 30 min. Tcn2 includes the candidate gene, uncoupling protein 2 (Ucp2), and shows linkage to Ucp2 mRNA levels in the soleus muscle (LOD = 4.90). Identification of six QTLs for diabetes-related traits in F(2)-D Tgf/Tgf and F(2)-C Tgf/Tgf raises the possibility of identifying candidate susceptibility genes and new targets for drug development for human type 2 diabetes.
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PMID:Diabetic modifier QTLs in F(2) intercrosses carrying homozygous transgene of TGF-beta. 1816 Sep 96

Insulin resistance plays a central role in type 2 diabetes and obesity, which develop as a consequence of genetic and environmental factors. Dietary changes including high fat diet (HFD) feeding promotes insulin resistance in rodent models which present useful systems for studying interactions between genetic background and environmental influences contributing to disease susceptibility and progression. We applied a combination of classical physiological, biochemical and hormonal studies and plasma (1)H NMR spectroscopy-based metabonomics to characterize the phenotypic and metabotypic consequences of HFD (40%) feeding in inbred mouse strains (C57BL/6, 129S6, BALB/c, DBA/2, C3H) frequently used in genetic studies. We showed the wide range of phenotypic and metabonomic adaptations to HFD across the five strains and the increased nutrigenomic predisposition of 129S6 and C57BL/6 to insulin resistance and obesity relative to the other strains. In contrast mice of the BALB/c and DBA/2 strains showed relative resistance to HFD-induced glucose intolerance and obesity. Hierarchical metabonomic clustering derived from (1)H NMR spectral data of the strains provided a phylometabonomic classification of strain-specific metabolic features and differential responses to HFD which closely match SNP-based phylogenetic relationships between strains. Our results support the concept of genomic clustering of functionally related genes and provide important information for defining biological markers predicting spontaneous susceptibility to insulin resistance and pathological adaptations to fat feeding.
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PMID:Phylometabonomic patterns of adaptation to high fat diet feeding in inbred mice. 1830 46

For experimental research on type 2 diabetes mellitus, a diet-induced obesity-dependent diabetes model developed using genetically normal animals is essential. However, attempts at feeding a high-fat diet (HFD) to major inbred strains of mice have not resulted in the establishment of an ideal model. Here, we show that BDF1 mice, the F(1) hybrids of C57BL/6 and DBA/2 normal strains, develop HFD-induced obesity-dependent diabetes. BDF1 mice fed a HFD gained weight rapidly and developed severe diabetes characterized by hyperglycemia, glucosuria, and elevation of hemoglobin A(1C) levels in 3 to 4 months. The glucose tolerance of the diabetic mice was significantly impaired, and the elevation of plasma insulin after a glucose load was significantly reduced. Isolated pancreatic islets of HFD-fed BDF1 mice showed decreased insulin content and a reduced insulin secretory response to higher concentrations of glucose. Immunohistochemical analysis of the pancreas showed reduced staining intensity to insulin and aberrant distribution of glucagon-positive cells in diabetic BDF1 mice. These observations suggest the cause of the diabetes in HFD-fed BDF1 mice to be dysfunction of the pancreatic beta-cells, which do not produce or secrete enough insulin to compensate for insulin resistance. BDF1 mice fed a HFD showing obesity-dependent diabetes are suggested to be an appropriate animal model of type 2 diabetes mellitus. This model would be useful for exploring the mechanism of obesity-dependent type 2 diabetes mellitus and evaluating antiobesity and antidiabetic drugs.
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PMID:A novel model of type 2 diabetes mellitus based on obesity induced by high-fat diet in BDF1 mice. 1921 42


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