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)

The inability to secrete the water-soluble glycoprotein form of the ABO blood group antigens is a genetic characteristic associated with susceptibility to superficial fungal infections and also insulin-dependent diabetes mellitus (IDDM). As oral carriage of Candida albicans in healthy adults is associated with non-secretion, we examined oral carriage of yeasts among 275 patients attending diabetic outpatient clinics, 137 with IDDM and 138 with non-insulin dependent diabetes mellitus (NIDDM) with reference to ABO blood group, secretor status and yeast species. Of the 166 yeast isolates, 109 (66.7%) were C. albicans, a lower proportion compared with 94% reported for healthy individuals. There was no association between ABO blood group and carriage. There was no increase in the proportion of non-secretor carriers of C. albicans among patients with IDDM; but among those with NIDDM, 44% of non-secretors were carriers compared with 21% who were non-carriers (p less than 0.01). The results are discussed in the context of host-parasite interactions influencing colonization.
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PMID:Blood group, secretor status and oral carriage of yeasts among patients with diabetes mellitus. 269 83

Plasma fibronectin (FN) is a high-molecular weight glycoprotein produced by endothelial cells, fibroblasts, and other mesenchymal cells. Plasma FN levels were measured in non-insulin-dependent diabetics (NIDDM) (n = 42) and compared with age-matched control subjects (n = 20). Plasma FN levels were significantly higher in the NIDDM patients (44.2 +/- 2.2 mg/dl, mean +/- SE) than in the control subjects (31.2 +/- 2.2 mg/dl). In addition, the rate of platelet aggregation was studied in 23 of the 42 NIDDM patients. Interestingly, the plasma FN levels were significantly elevated, particularly in diabetic patients with enhanced platelet aggregation. It is suggested that elevated plasma FN may be closely related to the abnormality of platelet function in diabetics, which leads to diabetic vascular lesions.
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PMID:Plasma fibronectin and platelet aggregation in diabetes mellitus. 372 May 1

Insulin receptor is a membrane-bound glycoprotein playing a key role in transmembrane signaling of insulin. Therefore, it is logical to look for abnormal structure or functions of this protein in insulin resistance syndromes, such as major insulin resistance syndromes and non insulin dependent diabetes mellitus. Cloning of the insulin receptor cDNA allowed to identify the functional domains of the protein (insulin binding site, autophosphorylation sites and tyrosine-kinase domain). Mutations of the insulin receptor gene are often observed in rare syndromes of major insulin resistance, such as leprechaunism, type A insulin resistance and Rabson-Mendenhall syndrome. However, such studies are disappointing in the case of NIDDM, in which defects of other proteins involved in insulin action should be investigated.
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PMID:[Insulin receptor and diabetes]. 793 36

We examined the plasma protein binding of an acidic drug (warfarin bound to albumin) and a basic drug [lidocaine (lignocaine) bound to alpha 1-acid glycoprotein] in 15 patients with insulin-dependent diabetes mellitus (IDDM) and 15 matched controls. We also examined protein binding of warfarin and lidocaine in 30 patients with non-insulin-dependent diabetes (NIDDM) and 25 controls. Compared with control, the binding of both warfarin (98.81 +/- 0.02 vs 98.57 +/- 0.03%, mean +/- SEM) and of lidocaine (69 +/- 2 vs 58 +/- 2%) was significantly reduced in IDDM. This group had lower concentrations of both albumin and alpha 1-acid glycoprotein (AAG), achieving statistical significance vs control for albumin only. In the patients with NIDDM, who had a similar level of glycosylated haemoglobin, while there was no significant difference in the binding of lidocaine there was a significant increase in warfarin binding compared with the control population (99.01 +/- 0.03 vs 98.82 +/- 0.04%). This study suggests that binding of both acidic and basic drugs is altered in both IDDM and NIDDM.
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PMID:Plasma protein binding of lidocaine and warfarin in insulin-dependent and non-insulin-dependent diabetes mellitus. 845 25

Membrane glycoprotein PC-1, an inhibitor of insulin signaling, produces insulin resistance when overexpressed in cells transfected with PC-1 cDNA. In the present study, we determined whether PC-1 plays a role in the insulin resistance of skeletal muscle in obesity. Rectus abdominus muscle biopsies were taken from patients undergoing elective surgery. Subjects included both NIDDM patients (n = 14) and nondiabetic patients (n = 34) across a wide range of BMI values (19.5-90.1). Insulin-stimulated glucose transport was measured in incubated muscle strips, and PC-1 content, enzymatic activity, and insulin receptor content were measured in solubilized muscle extracts. Increasing BMI correlated with both an increase in the content of PC-1 in muscle (r = 0.55, P < 0.001) and a decrease in insulin stimulation of muscle glucose transport (r = -0.58, P = 0.008). NIDDM had no effect on either PC-1 content or glucose transport for any given level of obesity. Insulin stimulation of muscle glucose transport was negatively related to muscle PC-1 content (r = -0.68, P = 0.001) and positively related to insulin receptor content (r = 0.60, P = 0.005). Multivariate analysis indicated that both skeletal muscle PC-1 content and insulin receptor content, but not BMI, were independent predictors of insulin-stimulated glucose transport. Muscle PC-1 content accounted for 42% and insulin receptor content for 17% of the variance in glucose transport values. These studies raise the possibility that increased expression of PC-1 and a decreased insulin receptor content in skeletal muscle may be involved in the insulin resistance of obesity.
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PMID:Skeletal muscle content of membrane glycoprotein PC-1 in obesity. Relationship to muscle glucose transport. 882 66

Non-insulin-dependent diabetes mellitus (NIDDM) is commonly associated with hypertriglyceridaemia, low serum HDL-cholesterol concentrations, hypertension, obesity and accelerated atherosclerosis (metabolic syndrome X). Since a similar dyslipidaemia occurs with the acute-phase response, we investigated whether elevated acute-phase/stress reactants (the innate immune system's response to environmental stress) and their major cytokine mediator (interleukin-6, IL-6) are associated with NIDDM and syndrome X, and may thus provide a unifying pathophysiological mechanism for these conditions. Two groups of Caucasian subjects with NIDDM were studied. Those with any 4 or 5 features of syndrome X (n = 19) were compared with a group with 0 or 1 feature of syndrome X (n = 25) but similar age, sex distribution, diabetes duration, glycaemic control and diabetes treatment. Healthy non-diabetic subjects of comparable age and sex acted as controls. Overnight urinary albumin excretion rate, a risk factor for cardiovascular disease, was also assayed in subjects to assess its relationship to the acute-phase response. Serum sialic acid was confirmed as a marker of the acute-phase response since serum concentrations were significantly related to established acute-phase proteins such as alpha-1 acid glycoprotein (r = 0.82, p < 0.0001). There was a significant graded increase of serum sialic acid, alpha-1 acid glycoprotein, IL-6 and urinary albumin excretion rate amongst the three groups, with the lowest levels in non-diabetic subjects, intermediate levels in NIDDM patients without syndrome X and highest levels in NIDDM patients with syndrome X. C-reactive protein and cortisol levels were also higher in syndrome X-positive compared to X-negative patients and serum amyloid A was higher in both diabetic groups than in the control group. We conclude that NIDDM is associated with an elevated acute-phase response, particularly in those with features of syndrome X. Abnormalities of the innate immune system may be a contributor to the hypertriglyceridaemia, low HDL cholesterol, hypertension, glucose intolerance, insulin resistance and accelerated atherosclerosis of NIDDM. Microalbuminuria may be a component of the acute-phase response.
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PMID:NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. 2212 8

We set out to determine the genotype distributions of the PI(A) polymorphism of platelet glycoprotein IIIa, the HPA-3 polymorphism of platelet glycoprotein IIb, and the variable number tandem repeat (VNTR) polymorphism of platelet glycoprotein Ib in subjects with Type 2 diabetes mellitus (Type 2 DM) with (n = 125) and without (n = 90) a clinical history of macrovascular disease. In 215 white European subjects with Type 2 DM, presence of coronary artery disease was determined as a clinical history of angina, myocardial infarction (MI), coronary angioplasty or coronary artery by-pass grafting. Presence of peripheral vascular disease was defined as a clinical history of intermittent claudication with confirmatory vascular ultrasound or angiography, intermittent claudication with undetectable foot pulses and no history of arthralgia or surgery for leg ischaemia, confirmed by reference to medical case notes. Polymorphisms were detected by polymerase chain reaction amplification of DNA. There was no difference in the genotype distributions of subjects with and without macrovascular disease. In subjects with a first MI before the age of 60 years (n = 26), there was a 38% incidence of PI(A2) compared to 29% in subjects free from clinically evident macrovascular disease, but this difference did not reach statistical significance. This study does not support the hypothesis that polymorphisms of platelet glycoproteins, in particular the PI(A) polymorphism of platelet glycoprotein IIIa, play an important role in the pathogenesis of macrovascular disease in subjects with Type 2 DM.
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PMID:Polymorphisms of platelet glycoproteins in relation to macrovascular disease in type 2 diabetes mellitus. 958 97

Membrane glycoprotein plasma cell 1 (PC-1) has been shown to be increased in type 2 diabetes and involved in insulin resistance through inhibiting the insulin receptor tyrosine kinase, which was demonstrated using cultured breast cancer cells. However, other reports have shown contradictory results in Chinese hamster ovary cells and in vitro kinase assay. Thus, we considered it necessary to investigate the effect of PC-1 using highly insulin-sensitive cells. Here, we used two of the following approaches: 1) investigating PC-1 expression levels in insulin-responsive tissues in rat models of diabetes and 2) overexpressing PC-1 in 3T3-L1 adipocytes. We found that PC-1 was highly expressed in insulin-responsive tissues, such as liver and adipose tissue, in normal rats. However, high-fat feeding or streptozotocin-induced diabetes did not change its expression levels in liver, adipose tissue, and skeletal muscle. Thus, PC-1 expression levels were not associated with high-fat-diet-induced insulin resistance or hyperglycemia. Although PC-1 was increased in adipose tissue in Zucker fatty rats (protein level, by 50%; mRNA level, by 90%), its expression levels in liver and skeletal muscle, tissues that are more responsible for whole body glucose metabolism than adipose tissue, did not significantly differ from those in normal rats. Next, we overexpressed PC-1 in 3T3-L1 adipocytes using an adenovirus transfection system. PC-1 expression was markedly increased to a level 16-fold greater than that in normal human adipose tissue, which is higher than the previously reported levels in diabetic patients. However, insulin-induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1, activation of phosphatidylinositol 3-kinase, and glucose uptake were not affected by PC-1 overexpression. These results strongly suggest that increased PC-1 expression is not causally related to insulin resistance.
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PMID:No correlation of plasma cell 1 overexpression with insulin resistance in diabetic rats and 3T3-L1 adipocytes. 1038 40

The genes responsible for insulin resistance are poorly defined. Plasma cell differentiation antigen (PC-1) glycoprotein inhibits insulin receptor signaling and is associated with insulin resistance. We describe here a novel polymorphism in exon 4 of the PC-1 gene (K121Q) and demonstrate that it is strongly associated with insulin resistance in 121 healthy nonobese (BMI <30 kg/m2) nondiabetic (by oral glucose tolerance test [OGTT]) Caucasians from Sicily. Compared with 80 KK subjects, Q allele carriers (n = 41, 39 KQ and 2 QQ) showed higher glucose and insulin levels during OGTT (P < 0.001 by two-way analysis of variance) and insulin resistance by euglycemic clamp (M value = 5.25 +/- 1.38 [n = 24] vs. 6.30 +/- 1.39 mg x kg(-1) x min(-1) [n = 49], P = 0.005). Q carriers had higher risk of being hyperinsulinemic and insulin resistant (odds ratio [CI]: 2.99 [1.28-7.0], P < 0.001). Insulin receptor autophosphorylation was reduced (P < 0.01) in cultured skin fibroblasts from KQ versus KK subjects. Skeletal muscle PC-1 content was not different in 11 KQ versus 32 KK subjects (33 +/- 16.1 vs. 17.5 +/- 15 ng/mg protein, P = 0.3). These results suggest a cause-effect relationship between the Q carrying genotype and the insulin resistance phenotype, and raise the possibility that PC-1 genotyping could identify individuals who are at risk of developing insulin resistance, a condition that predisposes to type 2 diabetes and coronary artery disease.
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PMID:A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance. 1048 Jun 24

Platelets might be involved in the pathogenesis of diabetic microangiopathy. Wide interindividual variations in the density of a platelet collagen receptor (alpha2beta1 integrin or glycoprotein Ia/IIa) are reportedly associated with polymorphism(s) in the gene encoding the alpha subunit of the receptor, including a Bgl II polymorphism in intron 7. The aim of the present study was to determine the relationship between the Bgl II polymorphism and the susceptibility to diabetic microangiopathy. A case-control study comparing 227 patients with type II diabetes mellitus (119 with versus 108 without diabetic retinopathy) as well as 169 nondiabetic subjects demonstrated that genotypes with Bgl II (+) allele had a significant increase in the risk for retinopathy. The odds ratio for Bgl II (+/+) to Bgl II (-/-) was 3.41 (95% CI, 1.49-7.78, P =.0036) when analysis was confined to those with a disease duration of diabetes of 10 years or more. The present study suggests that the presence of a Bg II (+) allele is a genetic risk factor for diabetic retinopathy. (Blood. 2000;95:1560-1564)
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PMID:Association between diabetic retinopathy and genetic variations in alpha2beta1 integrin, a platelet receptor for collagen. 1068 8


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