Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three families with abnormal insulinemia have been reported in Japan and sequencing analysis revealed that they had the same point mutation in one allele of the insulin genes causing [Leu A3]insulin. To estimate whether or not this same mutation came from a common ancestor we determined the sequence of the hypervariable region 5'-flanking the third [Leu A3]insulin allele (insulin Tochigi). This region is composed of 42 tandem repeating oligonucleotides, is 599 base pairs long and the sequence is 5' cdi jfa faa aba baa aaa fab aaa caa aac aca cba aaf ccb 3' (abbreviated as a = ACAGGGGTGTGGGG; b = ACAGGGGTCTGGGG; c = ACAGGGGTCCTGGGG; d = ACAGGGGTCCGGGG; f = ACAGGGGTCCCGGGG; i = ACAGGGTCCTGGGG; j = ACAGGGGTGTGAGG). The length of this region is different from those of the first and second [Leu A3]insulin alleles (insulin Wakayama I,II). This difference suggests either that insulin Tochigi and insulin Wakayama I,II are not of the same origin, or that three cases of [Leu A3]insulin in Japan have the same ancestor but recombination has occurred in this region at some point in the past.
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PMID:Hypervariable region 5'-flanking [Leu A3]insulin gene of insulin Tochigi is different from those of insulin Wakayama I,II. 218 61

A 64-year-old man undergoing abdominal aortic aneurysm repair with no history of diabetes mellitus had an episode of marked hyperglycemia during surgery. The peak concentration of glucose in plasma was 43.2 mmol/L. This hyperglycemia responded immediately to administration of 30 units of regular insulin. Factors involved in the hyperglycemia included surgical stress, multiple medications, and the anesthetic used (isoflurane), but do not fully account for the magnitude of the increase in glucose. The data suggest that the patient may have had an underlying insulin deficiency, which was unmasked by the stress of surgery.
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PMID:Transient hyperglycemia during abdominal aortic surgery. 233 99

The goal of this study was to evaluate the presence of extrahepatic damage and the uniformity and reversibility of the histological findings in CCl4-induced liver cirrhosis in the rat. To verify these findings rats were sacrificed 2 and 10 weeks after a treatment consisting of ten intragastric doses of CCl4, administered weekly. All treated rats developed an irreversible micronodular cirrhosis with no damage to the brain, kidney and pancreas. Moreover, rats sacrificed 2 weeks after the last CCl4 dose showed a number of functional alterations usually observed in man. In particular, low branched chain/aromatic amino acids (BCAA/AAA) plasma ratio, high ammonia, low zinc and high insulin with normal blood glucose were obtained.
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PMID:Carbon tetrachloride-induced experimental cirrhosis in the rat: a reappraisal of the model. 262 82

To clarify the clinical significance of specific plasma amino acid abnormalities occurring in liver disorders with portal-systemic shunting, plasma amino acids and insulin levels were measured in idiopathic portal hypertension (IPH), extrahepatic portal occulusion (EHPO), and liver cirrhosis (LC). Three branched chain amino acids (BCAA: valine + leucine + isoleucine) were decreased in all three diseases in comparison with controls. Since plasma insulin measured during oral glucose tolerance tests did not specifically rise in LC, reduction of BCAA is not merely ascribed to hyperinsulinemia. Either portal-systemic shunting or some extent of liver damage may contribute to a fall in BCAA. Two aromatic amino acids (AAA: phenylalanine + tyrosine), which were within the normal range in EHPO and IPH, showed a marked increase in LC. Thus, changes of AAA probably mainly reflect the severity of the liver disease. The molar ratio of BCAA/AAA (MR) significantly correlated with ICG k, ICG R15, PT and the sum of blood ammonia in an oral ammonia tolerance test which may reflect the degree of hepatic disorder. MR diminished in the following decreasing order: controls, EHPO, IPH and LC.
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PMID:Plasma amino acid abnormalities in liver disease: comparative analysis of idiopathic portal hypertension, extrahepatic portal occlusion and liver cirrhosis. 277 20

Changes in amino acid concentrations in plasma during a 100 g oral glucose tolerance test were investigated in patients with liver cirrhosis and in healthy controls. In the controls, almost all amino acid concentrations reached a nadir about 3 hours after glucose loading, then returned to initial levels after 6 hours. Immunoreactive insulin levels reached a peak about 30 minutes after loading, then decreased gradually, reaching initial levels after 6 hours. In the controls, the decrease ratios, defined as maximum decrease during the 3 hours after loading/initial concentration in plasma, were 0.607 and 0.554 for isoleucine (Ile) and leucine (Leu) respectively and 0.382 for valine (Val) which is significantly lower than for Ile or Leu. A similar tendency was recognized in patients with liver cirrhosis. The initial concentration of tyrosine (Tyr) and phenylalanine (Phe) in liver cirrhosis was significantly higher and their decrease ratios were significantly lower than in controls. Though no difference was observed between initial concentrations of tryptophan (Trp) in controls and liver cirrhosis patients, the decrease ratio of Trp in liver cirrhosis was lower (0.061) than that of controls (0.279) (p less than 0.001). The value, t-Trp/BCAA + AAA, i.e. total Trp concentration (mmol/l)/concentration (mmol/l) of branched chain amino acids (BCAA, Ile + Leu + Val) plus aromatic amino acids (AAA, Tyr + Phe), which is known to correlate with the brain Trp concentration of rats (Fernstrom, J. D. & Wurtman, R. J. (1972) Science 178, 414-416), changed significantly from 9.6 +/- 2.4 (mean +/- 1 SD) at the initiation to 12.9 +/- 3.3 at 3 hours after loading in controls (p less than 0.001), and in liver cirrhosis it changed from 10.3 +/- 1.9 to 15.8 +/- 3.1 (p less than 0.001).
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PMID:Changes in plasma amino acids during the oral glucose tolerance test and the effect of these changes on hepatic encephalopathy. 389 65

Plasma amino acid, plasma pancreatic glucagon and serum insulin levels were simultaneously measured in cirrhotic patients with (drinkers) and without a history of alcohol drinking (non-drinkers), as compared to those in alcoholics without liver disease. Clinical characteristics in drinkers and non-drinkers, such as the extent of liver dysfunction, which may affect plasma amino acid levels, were strictly matched. Plasma pancreatic glucagon levels in the drinker group were much higher than those in the non-drinker group. In the former group, the elevated plasma pancreatic glucagon levels were correlated (p less than 0.05) to total amino acid levels (the sum of 20 kinds of L-amino acid concentrations) and, elevated AAA concentrations leading to a diminished BCAA/AAA ratio. Drinkers with histories of hepatic encephalopathy presented grossly elevated glucagon levels and severely abnormal aminograms similar to those observed in hepatic insufficiency.
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PMID:Characteristic features of plasma amino acid, plasma pancreatic glucagon, serum insulin concentrations in cirrhotic patients with histories of chronic alcohol consumption. 637 63

Kir6.2 is an inwardly rectifying potassium channel that is expressed in pancreatic beta-cells and cardiac and skeletal muscle. Expressed together with the high-affinity sulphonylurea receptor, it reconstitutes a sulphonylurea- and also ATP-sensitive potassium channel resembling the native beta-cell channel. The objective of this study was to search for mutations in the Kir6.2 gene that might be associated with NIDDM or related to altered insulin secretion, insulin action, or glucose metabolism in healthy subjects. Using polymerase chain reaction-single-strand conformation polymorphism analysis (PCR-SSCP) on genomic DNA from 69 Danish NIDDM patients and 66 matched control subjects, we report the finding of three missense polymorphisms in otherwise conserved codons and three silent polymorphisms in the gene encoding Kir6.2: codon 23 (GAG/AAG), Glu-->Lys; codon 190 (GCT/GCC), Ala-->Ala; codon 267 (CTC/CTG), Leu-->Leu; codon 270 (CTG/GTG), Leu-->Val; codon 337 (ATC/GTC), Ile-->Val; codon 381 (AAG/AAA), Lys-->Lys. The codon 23 and codon 337 amino acid polymorphisms were always coupled. The allelic frequencies of the polymorphisms were similar in NIDDM patients and control subjects. The amino acid polymorphisms were not associated with altered insulin secretion after intravenous glucose or tolbutamide injections or with altered glucose effectiveness in a phenotype study of 346 young healthy subjects. However, carriers of the maximal load of amino acid variants, the compound homozygous codon 23/337 and heterozygous codon 270, had on average a 62% higher insulin sensitivity index (P = 0.006), compared with noncarriers. We conclude that a combination of common Kir6.2 amino acid variants may contribute to the genetic background behind the large variation of the insulin sensitivity index in the general population.
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PMID:Amino acid polymorphisms in the ATP-regulatable inward rectifier Kir6.2 and their relationships to glucose- and tolbutamide-induced insulin secretion, the insulin sensitivity index, and NIDDM. 903 10

The disturbances in the balance of pro- and antifibrinolytic activity, as observed in AAA and obesity, respectively, have considerable potential for influencing both intra- and extravascular fibrinolytic events and may be causally related to the development of vascular disease. For example, the wall of the aortic atherosclerotic aneurysm seems to host an uneven distribution and imbalanced expression of the various components of the fibrinolytic system. The sites of increased proteolytic activity may contribute to localized neovascularization and promote the rapid breakdown of ECM components, which result in mural weakening and eventual rupture of untreated aortic aneurysms. On the other hand, the disturbance of the normal hemostatic balance observed in obesity appears to result from the elevated expression of PAI-1 by the adipose tissue. Our data strongly suggest that the adipocyte is one of the primary cells in the adipose tissue capable of expressing PAI-1 both in obesity, and in response to cytokines and hormones like TNF-alpha and insulin. Since both TNF-alpha and insulin are known to increase in obesity, the elevated levels of PAI-1 observed in the plasma of obese individuals may result from TNF-alpha and/or insulin induction of PAI-1 in the adipose tissue itself.
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PMID:Expression of fibrinolytic genes in tissues from human atherosclerotic aneurysms and from obese mice. 918 10

L6 myoblasts stably transfected with a GLUT4 cDNA harboring an exofacial myc epitope tag (L6-GLUT4myc myoblasts) were used to study the role of protein kinase B alpha (PKBalpha)/Akt1 in the insulin-induced translocation of GLUT4 to the cell surface. Surface GLUT4myc was detected by immunofluorescent labeling of the myc epitope in nonpermeabilized cells. Insulin induced a marked translocation of GLUT4myc to the plasma membrane within 20 min. This was prevented by transient transfection of a dominant inhibitory construct of phosphatidylinositol (PI) 3-kinase (Deltap85alpha). Transiently transfected cells were identified by cotransfection of green fluorescent protein. A constitutively active PKBalpha, created by fusion of a viral Gag protein at its N terminus (GagPKB), increased the cell surface density of GLUT4myc compared to that of neighboring nontransfected cells. A kinase-inactive, phosphorylation-deficient PKBalpha/Akt1 construct with the mutations K179A (substitution of alanine for the lysine at position 179), T308A, and S473A (AAA-PKB) behaved as a dominant-negative inhibitor of insulin-dependent activation of cotransfected wild-type hemagglutinin (HA)-tagged PKB. Furthermore, AAA-PKB markedly inhibited the insulin-induced phosphorylation of cotransfected BAD, demonstrating inhibition of the endogenous PKB/Akt. Under the same conditions, AAA-PKB almost entirely blocked the insulin-dependent increase in surface GLUT4myc. PKBalpha with alanine substitutions T308A and S473A (AA-PKB) or K179A (A-PKB) alone was a less potent inhibitor of insulin-dependent activation of wild-type HA-PKB or GLUT4myc translocation than was AAA-PKB. Cotransfection of AAA-PKB with a fourfold DNA excess of HA-PKB rescued insulin-stimulated GLUT4myc translocation. AAA-PKB did not prevent actin bundling (membrane ruffling), though this response was PI 3-kinase dependent. Therefore, it is unlikely that AAA-PKB acted by inhibiting PI 3-kinase signaling. These results outline an important role for PKBalpha/Akt1 in the stimulation of glucose transport by insulin in muscle cells in culture.
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PMID:Protein kinase B/Akt participates in GLUT4 translocation by insulin in L6 myoblasts. 1033 Jan 41

The ATP-sensitive potassium channel (K(ATP)) regulates insulin secretion in pancreatic beta cells. Loss of functional K(ATP) channels because of mutations in either the SUR1 or Kir6.2 channel subunit causes persistent hyperinsulinemic hypoglycemia of infancy (PHHI). We investigated the molecular mechanism by which a single phenylalanine deletion in SUR1 (DeltaF1388) causes PHHI. Previous studies have shown that coexpression of DeltaF1388 SUR1 with Kir6.2 results in no channel activity. We demonstrate here that the lack of functional expression is due to failure of the mutant channel to traffic to the cell surface. Trafficking of K(ATP) channels requires that the endoplasmic reticulum-retention signal, RKR, present in both SUR1 and Kir6.2, be shielded during channel assembly. To ask whether DeltaF1388 SUR1 forms functional channels with Kir6.2, we inactivated the RKR signal in DeltaF1388 SUR1 by mutation to AAA (DeltaF1388 SUR1(AAA)). Inactivation of similar endoplasmic reticulum-retention signals in the cystic fibrosis transmembrane conductance regulator has been shown to partially overcome the trafficking defect of a cystic fibrosis transmembrane conductance regulator mutation, DeltaF508. We found that coexpression of DeltaF1388 SUR1(AAA) with Kir6.2 led to partial surface expression of the mutant channel. Moreover, mutant channels were active. Compared with wild-type channels, the mutant channels have reduced ATP sensitivity and do not respond to stimulation by MgADP or diazoxide. The RKR --> AAA mutation alone has no effect on channel properties. Our results establish defective trafficking of K(ATP) channels as a molecular basis of PHHI and show that F1388 in SUR1 is critical for normal trafficking and function of K(ATP) channels.
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PMID:Defective trafficking and function of KATP channels caused by a sulfonylurea receptor 1 mutation associated with persistent hyperinsulinemic hypoglycemia of infancy. 1122 35


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