Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance characterizes type 1 diabetes in patients with albuminuria. A PC-1 glycoprotein amino acid variant, K121Q, is associated with insulin resistance. We examined the impact of the PC-1 K121Q variant on the rate of decline of the glomerular filtration rate (GFR) by creatinine clearance derived from the Cockroft-Gault formula in 77 type 1 diabetic patients with albuminuria who were followed for an average of 6.5 years (range 2.5-15). Patients carrying the Q allele (n = 22; 20 with KQ and 2 with QQ genotypes) had a faster GFR decline than those patients with the KK genotype (n = 55) (median 7.2 vs. 3.7 ml x min(-1) x year(-1); range 0.16 to 16.6 vs. -3.8 to 16.0 ml x min(-1) x year(-1); P < 0.001). Significantly more patients carrying the Q allele belonged to the highest tertile of GFR decline (odds ratio = 5.7, 95% CI 4.1-7.2, P = 0.02). Levels of blood pressure, HbA1c, and albuminuria were comparable in the two genotype groups. Albuminuria (P = 0.001), mean blood pressure (P = 0.046), and PC-1 genotype (P = 0.036) independently correlated with GFR decline. Because all patients were receiving antihypertensive treatment, the faster GFR decline in the patients carrying the Q allele could be the result of reduced sensitivity to the renoprotective effect of antihypertensive therapy. PC-1 genotyping identifies type 1 diabetic patients with a faster progression of diabetic nephropathy.
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PMID:A PC-1 amino acid variant (K121Q) is associated with faster progression of renal disease in patients with type 1 diabetes and albuminuria. 1086 79

A polymorphism in the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene (ENPP1) (previously known as PC-1), resulting in an amino acid change from lysine to glutamine at codon 121 (K121Q), is associated with insulin resistance. A small follow-up study of patients with type 1 diabetes and proteinuria found that renal function declines more rapidly in carriers of the Q variant than in noncarriers. To examine this finding further, we conducted a large case-control study and a family-based study. Genomic DNA was obtained from 659 patients: 307 with normal urinary albumin excretion despite diabetes duration of >15 years (control subjects) and 352 with advanced diabetic nephropathy, of whom 200 had persistent proteinuria and 152 had end-stage renal disease (ESRD). Individuals were genotyped for Q and K variants using a previously described protocol. The frequency of Q variant carriers was 21.5% in control subjects, 31.5% in subjects with proteinuria, and 32.2% in subjects with ESRD (P = 0.012). In a stratified analysis according to duration of diabetes, the risk of early-onset ESRD for carriers of the Q variant was 2.3 times that for noncarriers (95% CI, 1.2-4.6). The Q variant was not associated with late-onset ESRD. Similar findings were obtained in a family-based study. We conclude that carriers of the Q variant of ENPP1 are at increased risk for developing ESRD early in the course of type 1 diabetes.
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PMID:Polymorphism in ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene (ENPP1/PC-1) and early development of advanced diabetic nephropathy in type 1 diabetes. 1191 43

Proinflammatory cytokines play a major role in rejection of pancreatic islet allografts and in type 1 diabetes (T1D). In rodent islets, exposure to IL-1beta alone or combined with IFN-gamma induces expression of inducible nitric oxide synthase (iNOS). Inhibition of iNOS or a deletion of the iNOS gene has been shown to be protective in animal models of T1D. In the present study we tested the hypothesis that transplantation of pancreatic islets deficient in iNOS (iNOS-/-) would permit increased graft survival. Pancreatic islets isolated from wild-type (wt) mice and iNOS-/- mice were allogeneically transplanted beneath the kidney capsule of spontaneously diabetic NOD mice. When blood glucose increased above 12.0 mM after preceding normalization of hyperglycemia, animals were sacrificed. Histological examinations of grafts were performed and graft gene expression was analyzed by real-time PCR. Transplantations of the two types of islets could reverse hyperglycemia and the grafts functioned for on average 1 week posttransplantation. Morphological examination of both types of islet grafts showed immune cell infiltration around and within the grafts. Remaining endocrine cells could be observed in wt and iNOS-/- islet grafts. In the removed grafts iNOS-/- islet tissue contained higher mRNA levels of insulin, proinsulin convertases (PC-1 and PC-2), and IL-1beta compared to transplanted wt islets. The assessments of insulin, PC-1 and PC-2 mRNAs of the grafts suggest that the iNOS-/- islets may be more resistant to destruction in the transplantation model used; however, this was not sufficient to prolong the period of normoglycemia posttransplantation.
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PMID:Survival of an islet allograft deficient in iNOS after implantation into diabetic NOD mice. 1726 47