Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We followed patients with pregnancy and diabetes in an outpatient clinic. 240 had gestational diabetes, 16 had type II and 5 type I diabetes. 85% of 110 patients with gestational diabetes had normal glucose tolerance test post partum (AGT). Type I patients were younger (25 years old) than AGT (32) or type II (33) patients. Complications frequently observed among diabetics included hypertension, premature membrane rupture and polyhydroamnios (the latter only among AGT and type II patients). Insulin was required for diabetes control in 14% of cases. Cesarean section was more frequent in diabetics than in a control population (21%): AGT 45%, type II 45% and type I 60%. Larger newborns occurred in 21% of AGT and 22% of type II as compared to 6% in controls. Neonatal mortality was 2.1% in AGT patients (0.8% in controls). Hyperbilirrubinemia, polyglobulia and hypocalcemia were more frequent among newborns of diabetic patients.
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PMID:[Clinical experience in diabetes and pregnancy]. 251 61

Two sisters presented with severe insulin resistance and markedly decreased insulin binding to erythrocytes, cultured fibroblasts and transformed lymphocytes. The dose-response curve of insulin-stimulated amino acid uptake in the fibroblasts was shifted to the right. The molecular weight of the insulin receptor on the transformed lymphocytes from the patients was 210,000 and could not be dissociated to alpha- and beta-subunits by dithiothreitol treatment. However, the proreceptor was cleaved by trypsin and this led to the production of alpha-subunit with normal insulin binding. We performed cDNA sequence analysis of the cleavage site of the insulin proreceptor from the patients. The polymerase chain reaction was used to obtain a large amount of cDNA coding for the region including the interconnecting site. A thermostable DNA polymerase, Taq polymerase, successfully produced enough cDNA for the region to be sequenced. The results showed an AGG (Arg) to AGT (Ser) point mutation, resulting in the change of the interconnecting sequence of the two subunits from -Arg-Lys-Arg-Arg- to -Arg-Lys-Arg-Ser-. These results suggest that the tertiary structure change of the cleavage site leads to production of unprocessed insulin proreceptors.
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PMID:Unprocessed insulin proreceptors due to point mutation at the cleavage site. 268 Mar 65

Failure to cleave the interconnecting site between alpha- and beta-subunit produced insulin proreceptors in the plasma membranes which had markedly low affinity to insulin, leading to extreme insulin resistance in a patient. We performed cDNA sequence analysis of the cleavage site of the insulin proreceptor from the patient. Polymerase chain reaction was used to obtain large amount of cDNA coding for the region including the interconnecting site. A thermostable DNA polymerase, Taq polymerase, successfully produced enough amount of cDNA of the region to be sequenced. The results showed AGG (Arg) to AGT (Ser) point mutation, resulting in the change of interconnecting sequence of the two subunits from -Arg-Lys-Arg-Arg- to -Arg-Lys-Arg-Ser-. These results suggest that the tertial structure change of the cleavage site leads to production of unprocessed insulin proreceptors.
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PMID:Insulin resistance by unprocessed insulin proreceptors point mutation at the cleavage site. 328 35

Glycated plasma proteins (GPP) and glycated hemoglobin (G Hb) has been evaluated in 134 non-diabetics (ND), 299 women with potential abnormality of glucose tolerance (pot.AGT), 75 with impaired glucose tolerance (IGT) and 34 insulin dependent diabetics (IDDM) during pregnancy or postpartum including 94 cord blood determinations. Mean HbA1c levels were significantly elevated in IDDM (6.6 +/- 1.3% M +/- SD) compared to ND (5.1 +/- 0.7%; P less than 0.01), but were similar for the other groups studied. Mean GPP were increased for the IDDM (0.58 +/- 0.29 nmol 5- HMF/mg protein; M +/- SD) and the IGT-group (0.53 +/- 0.22) over ND (0.3 +/- 0.13; P less than 0.01) and the Pot.AGT group (0.37 +/- 0.14; P less than 0.01). 6% of the ND, 15% of the Pot AGT-, 52% of the IGT- and 62% of the IDDM group were found to have GPP values exceeding the 97% confidential limit of the ND. However, the large overlap of individual values from patients with different degrees of glucose intolerance with the normal range of pregnancy precludes the use of GPP as a screening parameter for IGT during pregnancy. A 30-35% reduction of fetal hemoglobin- and plasma protein glycosylation relative to maternal values was observed.
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PMID:Glycated plasma proteins in normal and diabetic mothers and their offsprings. 346 46

Lipodystrophic diabetes mellitus of the Seip-Berardinelli type is a syndrome associated with insulin resistance and recessive inheritance. We have examined whether mutations in the insulin receptor are pathogenetic factors in this syndrome. Fibroblasts from three different patients with Seip-Berardinelli's lipodystrophy were tested for insulin binding, and insulin-stimulated receptor autophosphorylation. In addition, the coding region of both alleles of the iinsulin receptor gene was sequenced. No abnormalities in the number of high affinity insulin binding sites, and insulin-stimulated receptor autophosphorylation were detected. The insulin receptor related insulin-like growth factor I receptor also showed no functional changes. DNA sequence analysis of the amplified exons of the insulin receptor gene showed a silent mutation in patient 1 at codon Ser339, changing AGT to AGC. In patient 2 a heterozygous Met for Val substitution at position 985 was detected, which is a rare polymorphism. In patient 3 no mutations, other than described polymorphisms, were observed. These findings demonstrate that the primary genetic lesion in Seip-Berardinelli's lipodystrophy is outside the insulin receptor gene and that an involvement of the insulin-like growth factor I receptor is also unlikely.
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PMID:Patients with lipodystrophic diabetes mellitus of the Seip-Berardinelli type, express normal insulin receptors. 845 33

According to the "thrifty-genotype" hypothesis proposed by Neel, diseases of civilization such as non-insulin-dependent diabetes mellitus and hypertension result from a discordance between certain features of our present-day environment and our genetic make-up which evolved to fit the life of Paleolithic humans. This concept implies that while "affected" individuals harbor the "original" ancestral version of the relevant genes, healthy or "unaffected" individuals have picked up recent mutations leading to a "loss of thriftiness" of these genes. Support for this concept now comes from recent studies of the angiotensinogen gene, where an ancestral variant of the gene (AGT 235T), also present in primates, has now been associated with hypertension whereas a neomorphic variant (AGT 235M) apparently reduces the risk of high blood pressure. The implications of these findings for our understanding and approach to the study of complex genetic diseases is discussed.
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PMID:The thrifty-genotype hypothesis and its implications for the study of complex genetic disorders in man. 969 33

In a hospital cohort study, we examined whether or not ACE (Angiotensin-I converting enzyme) and AGT (Angiotensinogen) gene polymorphisms were associated with the development of nephropathy in long-term Japanese insulin-dependent diabetes mellitus (IDDM) patients with or without proliferative retinopathy, and whether or not the polymorphisms were associated with an arteriosclerotic family history in first degree relatives of the patients. A total of 201 patients with IDDM for more than 10 years and 159 patients with IDDM for more than 15 years were randomly selected in our hospital. All patients received uniform diabetes management and were divided into three groups, no nephropathy, incipient nephropathy and clinical nephropathy groups. There were no differences in clinical characteristics excluding urinary albumin to creatinine ratio and systolic blood pressure between the three groups. ACE I/D polymorphism was related to plasma ACE activity, but there were no associations between ACE I/D polymorphism and the development of diabetic nephropathy, nor was renal deterioration observed in patients with proliferative retinopathy even in those with a history of diabetes for more than 15 years. The AGT polymorphism did not have an additive effect on the association between ACE polymorphism and the development of diabetic nephropathy in patients with or without retinopathy. Development of diabetic nephropathy in the patients with or without proliferative retinopathy did not result in ACE or AGT polymorphisms. On the other hand, the ACE DD genotype was associated with a family history of ischemic heart disease in first degree relatives (X2 score = 9.04, P < 0.05). ACE and AGT gene polymorphisms may not play a role in the protective or accelerative effect against the development of diabetic nephropathy in the patients with or without proliferative retinopathy, but ACE gene polymorphism might be related to an arteriosclerotic family history in Japanese IDDM patients.
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PMID:Genetic polymorphism of renin-angiotensin system is not associated with diabetic vascular complications in Japanese subjects with long-term insulin dependent diabetes mellitus. 1049 84

Postprandial hyperglycemia has been shown to increase the risk of cardiovascular disease as much as overt diabetes mellitus does. The aim of this study was to determine whether isolated post-challenge hyperglycemia during an oral glucose tolerance test (OGTT) is related to exaggerated neointimal proliferation after coronary stent implantation. Forty seven coronary lesions treated with stents in 40 patients who had normal fasting glucose levels (<110 mg/dl) were categorized into the following 2 groups according to the results of a 75-g OGTT: 29 lesions in 24 patients with normal glucose tolerance (NGT group) and 18 lesions in 16 patients with abnormal glucose tolerance (AGT group). Although there were no differences in angiographic characteristics before and immediately after stenting between the 2 groups, the minimal lumen diameter was significantly smaller (p=0.04) and the degree of stenosis and late loss were also significantly greater (p=0.01 and p=0.047) in the AGT group than in the NGT group at 6-month follow-up. Multiple regression analysis including the insulin concentrations during an OGTT revealed that the 120-min plasma glucose concentration after glucose load significantly correlated with late loss (p=0.0018) and the degree of stenosis (p=0.0100) at follow-up. It is concluded that isolated post-challenge hyperglycemia exaggerates neointimal hyperplasia after coronary stent implantation.
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PMID:Isolated post-challenge hyperglycemia in patients with normal fasting glucose concentration exaggerates neointimal hyperplasia after coronary stent implantation. 1252 Jan 54

Insulin resistance is a determinant of blood pressure variation and risk factor for hypertension. Because insulin resistance and blood pressure cosegregate in Mexican American families, we thus investigated the association between variations in 9 previously reported hypertension genes (ACE, AGT, AGTRI, ADDI, NPPA, ADDRB2, SCNN1A, GNB3, and NOS3) and insulin resistance. Families were ascertained via a coronary artery disease proband in the Mexican American Coronary Artery Disease Project. Individuals from 100 Mexican American families (n=656) were genotyped for 14 polymorphisms in the 9 genes and all adult offspring and offspring spouses were phenotyped for insulin sensitivity by hyperinsulinemic euglycemic clamp (n=449). AGT M235T and NOS3 A(-922)G and E298D polymorphisms were significantly associated with insulin sensitivity (P=0.018, 0.036, 0.039) but were not significant after adjusting for body mass index. ADD1 G460W was associated with insulin sensitivity only after adjusting for body mass index. The NPPA T2238C and SCNN1A A663T were associated with decreased fasting insulin levels after adjusting for body mass index (P=0.015 and 0.028). In conclusion, AGT, NOS3, NPPA, ADRB2, ADD1, and SCNN1A may well be genetic markers for insulin resistance, and adiposity was a potential modifier for only some gene/trait combinations. Our data support the hypothesis that genes in the blood pressure pathway may play a role in insulin resistance in Mexican Americans.
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PMID:Hypertension genes are genetic markers for insulin sensitivity and resistance. 1569 55

This paper summarizes the new classification of diabetes mellitus (and other categories of glucose intolerance) and presents some clinically important aspects of the new insulins. The new classification promises to bring to the field considerable uniformity, previously lacking. The five clinical classes are: Type I (insulin-dependent diabetes mellitus, IDDM), Type II (non-insulin-dependent, NIDDM), "other types", gestational diabetes (GDM) and impaired glucose tolerance (IGT). The two statistical risk classes are: previous abnormality of glucose tolerance (Prev AGT) and potential abnormality of glucose tolerance (Pot AGT). These are mutually exclusive classes. Criteria recommended for use by clinicians and researchers are presented in detail, as well as information on the oral glucose test and normal glucose tolerance. Particular attention is drawn to the differences in glucose metabolism (tolerance) characteristics in non-pregnant adults, children and pregnant females. The new insulins are so called because of increased purity achieved by new purification methods. They are not new formulations or types of insulin. Contamination of insulin preparations by other hormones or compounds (e.g. glucagon, pro-insulin, pancreatic polypeptide) is now at a very low level.
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PMID:Diabetes update. 2128 88


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