Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of combined treatment with pioglitazone.HCl and metformin on diabetes and obesity were investigated in Wistar fatty rats, which are hyperglycaemic and hypertriglyceridaemic and have higher plasma levels of total ketone bodies than lean rats. 2. Plasma glucose was significantly decreased when pioglitazone.HCl or metformin was administered alone and combined treatment accentuated this decrease. The administration of pioglitazone.HCl, but not metformin, also decreased plasma levels of triglyceride and total ketone bodies. 3. The glycogen content of skeletal muscle was not increased by pioglitazone.HCl or metformin alone, but was increased by combined treatment (P=0.003, ANOVA). 4. Pioglitazone.HCl produced increased food intake and bodyweight in hyperphagic Wistar fatty rats; however, concurrent administration of metformin significantly ameliorated these pioglitazone.HCl-induced increases. 5. These results indicate that combined treatment with pioglitazone.HCl and metformin induces a marked hypoglycaemic effect accompanied by a reduction in plasma levels of total ketone bodies and prevention of excessive bodyweight gain in Wistar fatty rats. These favourable effects suggest that the combination would be beneficial in treating patients with type 2 diabetes.
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PMID:Effects of combined pioglitazone and metformin on diabetes and obesity in Wistar fatty rats. 1198 34

Both ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) are renoprotective beyond their effects on blood pressure (BP), but their widespread use is limited by their tendency to provoke hyperkalemia. The comparative effects of ACEI and ARB on potassium handling have not been investigated. The objective of this study was to determine whether there are differences in dynamic renal potassium handling between ACEI and ARB in response to an oral potassium challenge. This was a randomized crossover study of candesartan versus lisinopril titrated to control BP followed by an inpatient study of renal potassium handling in 24 hypertensive patients with type II diabetes mellitus (DMII) and preserved renal function. Following an oral potassium challenge (0.75 mmol/kg), differences in hourly serum K (mmol/L), rate of urinary potassium excretion (UkV, micromol/min), and fractional excretion of potassium (FEK) were assessed by repeated-measures ANOVA. Hourly UkV(p = .45) and FEK (p = .19) were similar for candesartan and lisinopril, although FEK at 2 hours for candesartan tended to exceed that for lisinopril (.34 [.04] vs. .26 [.03]) and approached significance (p = .096). UkVfor candesartan at hour 2 was 177 (26) and 121 (21) for lisinopril and also approached significance (p = .10). Serial serum potassium did not differ (p = .70). No statistical differences were discovered in renal potassium handling between candesartan and lisinopril in patients with DMII and preserved renal function. Whether there are differences between the drug classes in renal impairment remains to be determined.
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PMID:Comparative effects on dynamic renal potassium excretion of ACE inhibition versus angiotensin receptor blockade in hypertensive patients with type II diabetes mellitus. 1209 42

Polymorphism in the calpain-10 gene is linked to type 2 diabetes, insulin resistance, and decreased thermogenesis. In view of the role of beta-adrenoceptors in thermogenesis we investigated the relationship between beta(1)-, beta(2)-, and beta(3)-adrenoceptor-stimulated lipolysis in abdominal sc fat cells and 3 different previously described single nucleotide polymorphisms (SNPs) in the calpain-10 gene (SNP-19, SNP-43, and SNP-63). The study sample comprised 240 healthy subjects. A strong association between lipolytic beta(3)-receptor function in adipocytes and the SNP-19, which is a deletion/insertion (1/2) was observed in overweight subjects (body mass index, >25 kg/m(2)), but not in lean ones. No association was found between any of the polymorphisms and lipolytic function of either beta(1)- or beta(2)-receptors. Carriers of 1/1 in SNP-19 had 30-fold decreased lipolytic sensitivity of beta(3)-adrenoceptors in comparison to 1/2 or 2/2 carriers (P = 0.0019, by ANOVA). This was found in both genders and was not influenced by SNP-43 or SNP-63 in the calpain-10 gene or by the Trp(64)Arg polymorphism in the beta(3)-adrenoceptor gene. In conclusion, a deletion/insertion polymorphism in the calpain-10 gene (SNP-19) is associated with reduced beta(3)-adrenoceptor function in obesity. This could be of importance for regulating thermogenesis in overweight subjects.
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PMID:Calpain-10 gene polymorphism is associated with reduced beta(3)-adrenoceptor function in human fat cells. 1210 50

This study evaluated the fracture resistance of maxillary premolars with MOD cavity preparation and simulated periodontal ligament. The teeth were restored with silver amalgam (G1), Scotchbond Multi-Purpose Plus and silver amalgam (G2) and Panavia F and silver amalgam (G3). After restorations were made, the specimens were stored at 37 degrees C for 24 hours at 100% humidity and submitted to the compression test in the Universal Testing Machine (Instron). The statistical analysis of the results (ANOVA and Tukey Test) revealed that the fracture resistance of group 2 (G2=105.720 kgF) was superior to those of groups 1 (G1=72.433 kgF) and 3 (G3=80.505 kgF) that did not differ between them.
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PMID:Fracture resistance of premolars with bonded class II amalgams. 1212 Jul 71

Genetic factors play an important role in the pathogenesis of type 2 diabetes. The relevance to type 2 diabetes of the common polymorphism Glu23Lys in the potassium inward rectifier 6.2 (KIR6.2) gene is still controversial. The aim of this study was to assess whether this polymorphism influences beta-cell function, alpha-cell function, or insulin action. We therefore studied 298 nondiabetic subjects using an oral glucose tolerance test (OGTT) and 75 nondiabetic subjects using a hyperglycemic clamp (10 mmol/l) with additional glucagon-like peptide (GLP)-1 and arginine stimulation. The prevalence of the Lys allele was approximately 37%, and the Lys allele was associated with higher incremental plasma glucose during the OGTT (P = 0.03, ANOVA). Neither first- nor second-phase glucose-stimulated C-peptide secretion was affected by the presence of the polymorphism; nor were maximal glucose-, GLP-1-, or arginine-induced C-peptide secretion rates; nor was insulin sensitivity (all P > 0.7). However, the relative decrease in plasma glucagon concentrations during the 10 min after the glucose challenge was reduced in carriers of the Lys allele (10 +/- 3% decrease from baseline in Lys/Lys, 18 +/- 2% in Glu/Lys, and 20 +/- 2% in Glu/Glu; P = 0.01, ANOVA). In conclusion, our findings suggest that the common Glu23Lys polymorphism in KIR6.2 is not necessarily associated with beta-cell dysfunction or insulin resistance but with diminished suppression of glucagon secretion in response to hyperglycemia. Our findings thus confirm its functional relevance for glucose metabolism in humans.
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PMID:The prevalent Glu23Lys polymorphism in the potassium inward rectifier 6.2 (KIR6.2) gene is associated with impaired glucagon suppression in response to hyperglycemia. 1219 81

Packable resin composites may offer improved properties and clinical performance over conventional resin composites or dental amalgam. This in vitro study examined the cuspal stiffness of molars restored with a packable resin composite, a conventional posterior microfilled resin composite and amalgam. Forty-eight intact caries-free human third molars were distributed into four treatment groups (n=12) so that the mean cross-sectional areas of all groups were equal. Standardized MOD cavity preparations were made and specimens restored using one of four restorative materials: (1) a spherical particle amalgam (Tytin); (2) Tytin amalgam with a dentin adhesive liner (OptiBond Solo); (3) a conventional microfilled posterior resin composite (Heliomolar); (4) a packable posterior resin composite (Prodigy Posterior). Cuspal stiffness was measured using a Bionix 200 biomaterials testing machine (MTS). Specimens were loaded vertically to 300 N at a crosshead speed of 1.0 mm/minute. Stiffness was measured at 10 intervals: (1) prior to cavity preparation (intact); (2) following cavity preparation, but before restoration; (3) seven days after restoration; then (4) 1, 2, 3, 4, 5, 6 and 12 months after restoration. All specimens were stored at 37 degrees C in deionized water throughout the study and thermocycled (5 degrees/55 degrees C; 2000 cycles) monthly for 12 months. Repeated Measures ANOVA revealed significant differences among treatment groups over time (p<0.0001). Cavity preparation reduced cuspal stiffness by more than 60%. At 12 months, the cuspal stiffness of restored teeth was, on average, 58% that of intact specimens. Neither the packable nor the conventional resin composite increased cuspal stiffness over that of amalgam.
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PMID:The influence of a packable resin composite, conventional resin composite and amalgam on molar cuspal stiffness. 1221 72

The relatively low bond strengths of resin cements to dentin may result in poor interfacial adaptation of composite inlays. This study determined whether the interfacial adaptation of composite inlays could be improved by applying an adhesive system and a low viscosity microfilled resin to the prepared cavity walls before making an impression. Ten MOD cavities were prepared on extracted human premolars with gingival margins located above and below the cemento-enamel junction. A "resin coat" consisting of a self-etching primer system (Clearfil SE Bond) and a low viscosity microfilled resin (Protect Liner F) was applied to the cavities of half of the prepared teeth, while the remaining teeth served as non-coated control specimens. All the teeth were restored with composite inlays (Estenia) fabricated by the indirect method and cemented with a dual-cured resin cement (Panavia F). After finishing the margins with superfine burs, the bonded inlays were thermocycled between 4 degrees C and 55 degrees C for 400 cycles. Specimens were sectioned with a diamond saw and the tooth-restoration interfaces were observed with a confocal laser scanning microscope. The data were analyzed with two-way ANOVA and Fisher's PLSD test (p < 0.05). The percentage length of gap formation at the dentin-restoration interface of the "resin coated" teeth (7.1 +/- 3.5) was significantly less than that of the non-coated teeth (85.7 +/- 6.7) (p < 0.05). The concept of coating the prepared cavity with an adhesive system and a low viscosity microfilled resin resulted in observing fewer gaps at the internal dentin-restoration interface compared with the non-coated specimens.
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PMID:The effect of a "resin coating" on the interfacial adaptation of composite inlays. 1254 Jan 15

Recently, the diagnostic criteria for type 2 diabetes mellitus have been changed, but there are disagreements about which measurements should be used. In contrast to the American Diabetes Association (ADA), The World Health Organization (WHO) still recognizes fasting and 2-h glucose concentrations measured on either plasma or whole blood as diagnostic tools. Insulin sensitivity and insulin secretion are both assumed to be involved in the pathogenesis of type 2 diabetes. The oral glucose tolerance test (OGTT) for estimating insulin sensitivity and secretion is increasingly used, e.g. in intervention trials. The objectives of this study were to estimate the coefficients of intra-individual variation (CVw) of blood glucose and serum insulin concentrations from an OGTT as well as indices of insulin sensitivity (HOMA) and insulin secretion (delta insulin30/delta glucose30) derived from this test. Following duplicate OGTTs with a median interval of 13 days (range 1-87 days), the analytical, inter-individual, and intra-individual coefficients of variation were calculated by nested ANOVA. The CVw for fasting blood glucose (7%) was considerably lower than that for 2-h post-load glucose (15%), which was again lower than for the insulin concentrations and indices of insulin sensitivity and secretion. In conclusion, the intra-individual variation is larger for 2-h post-load glucose than for fasting glucose and may question the continued use of the 2-h post-load glucose value in the diagnosis of type 2 diabetes.
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PMID:Reproducibility of S-insulin and B-glucose responses in two identical oral glucose tolerance tests. 1256 20

Podocyte structural changes have been suggested to be involved in the pathogenesis of albuminuria in diabetes. We evaluated podocytes density, number, and structure in 67 white patients with type 2 diabetes: 21 normoalbuminuric (NA), 23 microalbuminuric (MA), and 23 proteinuric (P). Kidney function and biopsy studies were performed; 20 kidney donors served as control subjects. Electron microscopic morphometric analysis was used to estimate numerical density of podocytes per glomerulus [Nv(epi/glom)], filtration slit length density per glomerulus (FSLv/glom), and foot process width (FPW). The number of podocytes per glomerulus (Epi N/glom) was obtained by multiplying Nv(epi/glom) by mean glomerular volume. Nv(epi/glom) was significantly decreased in all type 2 diabetic groups compared with control subjects and was lower in MA and P than in NA (P < 0.0001, ANOVA). Epi N/glom was lower in MA and P patients compared with control subjects (P < 0.002, ANOVA); however, there were no significant differences among the type 2 diabetic groups. In addition, MA and P had decreased FSLv/glom and increased FPW compared with NA (P < 0.005 for both, ANOVA). The albumin excretion rate was inversely related to Nv(epi/glom) and FSLv/glom and directly to FPW (P < 0.0005 for all), whereas there was no correlation with Epi N/glom. In conclusion, changes in podocyte structure and density occur since the early stages of diabetic nephropathy and might contribute to increasing albuminuria in type 2 diabetic patients. These findings also suggest that in white type 2 diabetic patients, the density of podocytes may be functionally more relevant than the absolute number.
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PMID:Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes. 1266 76

Raised capillary pressure has been implicated in the formation of diabetic microangiopathy in type I diabetes, in which it is elevated in those with the earliest signs of diabetic kidney disease but remains normal in those without complications. In subjects with type 2 diabetes without complications, capillary pressure is normal, although alterations in the pressure waveforms suggested enhanced wave reflections. The nature of skin capillary pressure in subjects with type 2 diabetes and hypertension remains to be elucidated, as does the effect of blood pressure-lowering therapy on capillary pressure in these subjects. Three studies were performed in well-matched groups. First, capillary pressure was elevated in hypertensive subjects with type 2 diabetes compared with normotensive subjects with type 2 diabetes (20.2 [17.4 to 22.7] mm Hg versus 17.7 [16.1 to 18.9] mm Hg, respectively, P<0.03, Mann-Whitney U test). Second, no significant difference was detected between hypertensive subjects with type 2 diabetes and hypertensive subjects without type 2 diabetes (19.4 [15.8 to 21.3] mm Hg versus 17.2 [15.1 to 19.8] mm Hg, respectively, P=0.5, Mann-Whitney U test). Finally, patients with type 2 diabetes were recruited to a case-control study. Seven subjects received blood pressure-lowering therapy and 8 did not. Therapy reduced capillary pressure from 18.2 [15.8 to 20.1] mm Hg to 15.9 [15.4 to 17.0] mm Hg (P=0.024 ANOVA), in contrast to the lack of effect of time alone. Mean arterial pressure was reduced from 110 [102 to 115] mm Hg to 105 [101 to 111] mm Hg (P=0.006, ANOVA). These findings provide a plausible mechanism by which reducing arterial hypertension may reduce the risk of microangiopathy in type 2 diabetes.
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PMID:Capillary pressure in subjects with type 2 diabetes and hypertension and the effect of antihypertensive therapy. 1269 16


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