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)

Converging evidence has identified a potential association among Alzheimer's disease, glucose metabolism, insulin activity, and memory. Notably, type 2 diabetes, which is characterized by insulin resistance, may modulate the risk of Alzheimer's disease, and patients with Alzheimer's disease may have a greater risk for glucoregulatory impairments than do healthy older adults. In animal studies, it has been shown that raising blood glucose levels acutely can facilitate memory, in part, by increasing cholinergic activity, which is greatly diminished in patients with Alzheimer's disease. Other studies have confirmed that glucose administration can facilitate memory in healthy humans and in patients with Alzheimer's disease. Interestingly, glucose effects on memory appear to be modulated by insulin sensitivity (efficiency of insulin-mediated glucose disposal). Of course, the acute effects of glucose administration should be distinguished from the effects of chronic hyperglycemia (diabetes), which has been associated with cognitive impairments, at least in older adults. The relationship of insulin and memory has been more difficult to characterize. In animals, systemic insulin administration has been associated with memory deficits, likely due, in part, to hypoglycemia that occurs when exogenous insulin is not supplemented with glucose to maintain euglycemia. In healthy adults and patients with Alzheimer's disease, raising plasma insulin levels while maintaining euglycemia can improve memory; however, raising plasma glucose while suppressing endogenous insulin secretion may not improve memory, suggesting that adequate levels of insulin and glucose are necessary for memory facilitation. Clinical studies have corroborated findings that patients with Alzheimer's disease are more likely than healthy older adults to have reduced insulin sensitivity, and further suggest that apolipoprotein E genotype may modulate the effects of insulin on glucose disposal, memory facilitation, and amyloid precursor protein processing. Collectively, these findings support an association among Alzheimer's disease, impaired glucose metabolism, and reduced insulin sensitivity.
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PMID:Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimer's disease. 1509 77

We studied the effect of variation at the lipoprotein lipase (LPL) gene locus on the susceptibility of individuals with non-insulin dependent diabetes mellitus (NIDDM) in a population of 110 NIDDM patients and 91 controls. Our objective was to study the relationship between the LPL-Pvu II polymorphism and NIDDM and lipid metabolism. PCR-RFLP was used to determine the DNA polymorphism of the sixth intron of the LPL gene. The frequencies of the genotypes in case and control groups were 29.1 and 30.8% for P+/P+; 45.5 and 36.3% for P+/P-; 25.5 and 33% for P-/P- respectively. There was no significant difference in frequencies of genotypes between the two groups. Logistic regression analysis revealed that triacylglycerol (TAG) and apolipoprotein E levels were associated with NIDDM, whereas Pvu II genotypes were not found as independent risk factors for the disease. Overall this study demonstrates the role of the Pvu II polymorphism in the LPL gene in modulating plasma lipid/lipoprotein levels in patients with NIDDM.
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PMID:DNA polymorphism of Pvu II site in the lipoprotein lipase gene in patients with non-insulin dependent diabetes mellitus. 1554 43

In order to explore the association of apolipoprotein E (ApoE) gene polymorphism with cerebral infarction in type 2 diabetic patients of Han nationality in Northeast China , the genotypes of ApoE gene were analyzed by polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) in the 208 cases, including 69 cases in control (CON) group and 67 in type 2 diabetes mellitus (T2DM) group as well as 72 in type 2 diabetes mellitus with cerebral infarction (T2DMCI) group. Plasma lipid content in T2DMCI was also detected for 70 cases. The distribution of genotypes in ApoE gene,epsilon(2)epsilon(3),epsilon(3)epsilon(3) as well as epsilon(3)epsilon(4) was no significant difference in three groups (epsilon(2)epsilon(3) : 13.2%,epsilon(3)epsilon(3) : 67.6%,epsilon(3)epsilon(4) : 16.2%in CON group;epsilon(2)epsilon(3) : 19.4%,epsilon(3)epsilon(3): : 70.1%epsilon(3)epsilon(4) : 9%in T2DM group;epsilon(2)epsilon(3) : 15.2%,epsilon(3)epsilon(3) : 75%,epsilon(3)epsilon(4) : 4.2%in T2DMCI group). The allele frequencies of epsilon(2),epsilon(3) and epsilon(4) were not significantly different in the three groups, either(epsilon(2) : 9.6%,epsilon(3) : 82.4%,epsilon(4) : 8.1%in CON group; epsilon(2) :10.5%,epsilon(3) :84.3%,epsilon(4) : 5.2%in T2DM group; epsilon(2) :11.8%,epsilon(3) :84.7%,epsilon(4) : 3.5%in T2DMCI group). The levels of total cholesterol (TC), tryglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were not significantly different among the different genotypes in T2DMCI group. The study confirmed that the polymorphisms of ApoE gene are neither associated with the T2DMCI, nor with the levels of plasma lipid in T2DMCI.
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PMID:[Association study of apolipoprotein e gene polymorphism and cerebral infarction in type 2 diabetic patients]. 1573 Sep 56

It has been shown that apolipoprotein A-I (ApoA-I) stimulates the secretion of apolipoprotein E (ApoE) from human macrophages. ApoA-I is a major protein constituent of HDL which because of its role in reverse cholesterol transport, has been implicated in the prevention of atherosclerosis. We herein investigated the ability of monocyte-derived macrophages (MDMs) in 42 patients with type 2 diabetes to secrete ApoE; these patients commonly have low plasma HDL and ApoA-I levels. Our data showed that ApoE secretion from these cells was reduced in patients with low plasma HDL and ApoA-I levels; there were positive correlation between ApoE secretion from MDMs and plasma HDL (r2=0.33, p=0.03) and ApoA-I (r2=0.31, p=0.03). Furthermore, we found that ApoE secretion increased concomitantly with an increase in HDL or ApoA-I in treated diabetics (n=24) from 1.99+/-1.86 to 3.40+/-1.77 ng/mg cell protein. These findings suggest another possible link between HDL and ApoA-I metabolism and atherosclerosis in patients with type 2 diabetes.
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PMID:Evaluation of apolipoprotein E secretion by macrophages in type 2 diabetic patients: role of HDL and apolipoprotein A-I. 1600 61

Upstream transcription factor 1 (USF1), the first gene associated with familial combined hyperlipidemia (FCHL), regulates numerous genes of glucose and lipid metabolism. Phenotypic overlap between FCHL, type 2 diabetes and the metabolic syndrome makes this gene an intriguing candidate in the disease process of these traits as well. As no disease-associated mutations in the coding region of USF1 have been identified, we addressed the functional role of intronic single nucleotide polymorphisms (SNPs) which define the FCHL-risk alleles of USF1, and identified that a 20 bp DNA sequence, containing the critical intronic SNP, binds nuclear protein(s), representing a likely transcriptional regulatory element. This functional role is further supported by the differential expression of USF1-regulated genes in fat biopsy between individuals carrying different allelic variants of USF1. Importantly, apolipoprotein E (APOE) is the most downregulated gene in the risk individuals, linking the potential risk alleles of USF1 with the impaired APOE-dependent catabolism of atherogenic lipoprotein particles.
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PMID:USF1 and dyslipidemias: converging evidence for a functional intronic variant. 1607 49

The enzyme 11beta-hydroxysteroid dehydrogenase (HSD) type 1 converts inactive cortisone into active cortisol in cells, thereby raising the effective glucocorticoid (GC) tone above serum levels. We report that pharmacologic inhibition of 11beta-HSD1 has a therapeutic effect in mouse models of metabolic syndrome. Administration of a selective, potent 11beta-HSD1 inhibitor lowered body weight, insulin, fasting glucose, triglycerides, and cholesterol in diet-induced obese mice and lowered fasting glucose, insulin, glucagon, triglycerides, and free fatty acids, as well as improved glucose tolerance, in a mouse model of type 2 diabetes. Most importantly, inhibition of 11beta-HSD1 slowed plaque progression in a murine model of atherosclerosis, the key clinical sequela of metabolic syndrome. Mice with a targeted deletion of apolipoprotein E exhibited 84% less accumulation of aortic total cholesterol, as well as lower serum cholesterol and triglycerides, when treated with an 11beta-HSD1 inhibitor. These data provide the first evidence that pharmacologic inhibition of intracellular GC activation can effectively treat atherosclerosis, the key clinical consequence of metabolic syndrome, in addition to its salutary effect on multiple aspects of the metabolic syndrome itself.
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PMID:11beta-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice. 1610 9

The role of apolipoprotein E (apoE) genotypes in modulating plasma lipid and apolipoprotein levels was studied in 112 patients with Type 2 diabetes mellitus (T2DM) and 94 healthy individuals. ApoE genotypes were identified by PCR amplification and subsequent restriction endonuclease digestion. The apoE allele and genotype frequencies were similar in both the diabetic and control subjects. The apoE allele frequencies were found to be 74.3 for e3, 10.1 for e2, 15.6 for e4 in the diabetic group, and 68.1 for e3, 13.2 for e2 and 18.7 for e4 in the control group. Sex-specific genotypic distribution of apoE polymorphism did not differ between the study groups. To elucidate the association of apoE with lipid abnormalities with respect to gender, serum lipid and apolipoprotein levels were compared among apo e2 (e2/2 and e3/2), e3 (e3/3) and e4 (e4/3 and e4/4) groups of T2DM and control subjects. Apo e2 allele was found to be associated to triglycerides for both sexes, and associated to glucose, and BMI only in females. Subjects with e2 allele had higher levels of BMI, glucose and triglyceride in comparison to e3 and e4. Our data suggest that genetic variation at the apoE locus in Turkish subjects is a genetic factor that influences lipid levels. Further studies attempting to correlate apoE polymorphism with lipid profile in a large number of individuals would be helpful in establishing the true significance of this polymorphism in the Turkish population.
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PMID:Apolipoprotein E polymorphism in Turkish subjects with Type 2 diabetes mellitus: allele frequency and relation to serum lipid concentrations. 1629 48

Oxidative stress is implicated in atherogenesis, yet most clinical trials with antioxidants, particularly vitamin E, have failed to protect against atherosclerotic diseases. A striking exception is probucol, which retards atherosclerosis in carotid arteries and restenosis of coronary arteries after angioplasty. Because probucol has in vitro cellular-protective effects independent of inhibiting lipid oxidation, we investigated the mode of action of probucol in vivo. We used three models of vascular disease: apolipoprotein E-deficient mice, a model of atherosclerosis; rabbit aortic balloon injury, a model of restenosis; and carotid injury in obese Zucker rats, a model of type 2 diabetes. Unexpectedly, we observed that the phenol moieties of probucol were insufficient, whereas its sulphur atoms were required for protection. Probucol and its sulphur-containing metabolite, but not a sulphur-free phenolic analogue, protected via cell-specific effects on inhibiting macrophage accumulation, stimulating reendothelialization, and inhibiting vascular smooth muscle cell proliferation. These processes were mediated via induction of heme oxygenase-1 (HO-1), an activity not shared by vitamin E. Our findings identify HO-1 as the molecular target of probucol. They indicate 2-electron rather than radical (1-electron) oxidants as important contributors to atherogenesis, and point to novel lead compounds for therapeutic intervention against atherosclerotic diseases.
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PMID:Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging. 1660 77

We have examined the frequency of the EcoRI, XbaI and MspI RFLPs of the apolipoprotein B (apo B) gene in 110 type 2 diabetic patients and 91 healthy control subjects in order to ascertain whether variation in this gene may influence the development of non-insulin dependent diabetes mellitus (type 2 diabetes). Serum lipids including total-cholesterol (T-Chol), triacylglycerol (TAG), apolipoprotein E (apo E), apolipoprotein AI (apo AI), apolipoprotein B and lipoprotein (a) (Lp(a)) were analysed. Genomic DNA was extracted and the apo B polymorphic regions amplified by the polymerase chain reaction. Regions carrying EcoRI, XbaI, and MspI restriction sites present in the apo B gene were amplified and digested separately by the respective enzymes. No significant difference for genotypic frequencies was observed for the EcoRI, XbaI and MspI restriction sites in type 2 diabetic patients as compared to controls. Type 2 diabetic patients and controls with EcoRI +/+ and XbaI +/+ genotypes had higher apo E levels. The MspI +/+ genotype is more frequent in the patient and control groups with elevated T-Chol. Furthermore, the EcoRI -/-, XbaI -/-, and MspI +/+ genotypes were found to be significantly more frequent in type 2 diabetic patients with higher blood glucose levels. This study identifies the apo B gene polymorphisms in modulating plasma lipid/lipoprotein and glucose levels in patients with type 2 diabetes.
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PMID:Apolipoprotein B gene variants are involved in the determination of blood glucose and lipid levels in patients with non-insulin dependent diabetes mellitus. 1663 94

Plasma phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism. PLTP activity is elevated in patients with diabetes, a condition with strongly elevated risk for coronary heart disease. The aim of this study was to test the hypothesis that statins reduce PLTP activity and to examine the potential role of apolipoprotein E (apoE). PLTP activity and apoE were measured in patients with type 2 diabetes from the DALI (Diabetes Atorvastatin Lipid Intervention) Study, a 30-week randomized double-blind placebo-controlled trial with atorvastatin (10 and 80 mg daily). At baseline, PLTP activity was positively correlated with waist circumference, HbA(1c), glucose, and apoE (all P < 0.05). Atorvastatin treatment resulted in decreased PLTP activity (10 mg atorvastatin: -8.3%, P < 0.05; 80 mg atorvastatin: -12.1%, P < 0.002). Plasma apoE decreased by 28 and 36%, respectively (P < 0.001). The decrease in apoE was strongly related to the decrease in PLTP activity (r = 0.565, P < 0.001). The change in apoE remained the sole determinant of the change in PLTP activity in a multivariate model. The activity of PLTP in type 2 diabetes is decreased by atorvastatin. The association between the decrease in PLTP activity and apoE during statin treatment supports the hypothesis that apoE may prevent PLTP inactivation.
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PMID:Plasma phospholipid transfer protein activity is decreased in type 2 diabetes during treatment with atorvastatin: a role for apolipoprotein E? 1664 10


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