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  • 11
    ISSN: 1432-0428
    Keywords: Keywords Glucose-regulated gene ; cDNA subtraction ; gene expression ; polymerase chain reaction ; expressed sequence tag.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Various genes are differentially expressed in cells during cell differentiation, development, aging, and in pathological conditions. To identify and isolate the genes that are specifically and differentially expressed in cells, we established a ligation-mediated polymerase chain reaction (PCR)-based method for cDNA subtraction. As this method is PCR-based, when target genes are expressed at high levels relative to the driver (a control pool for subtraction), even a small amount of target genes can be amplified. By this newly developed PCR-based subtraction method, a set of genes regulated by glucose were identified in a mouse insulinoma cell line. This PCR-based and non-radioactive subtraction method will be a powerful tool for identification of novel genes, specifically and differentally expressed in cells. [Diabetologia (1996) 39: 1293–1298]
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1432-0428
    Keywords: Keywords Genetic susceptibility ; linkage disequilibrium ; association ; positional cloning ; microsatellite marker.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An insulin-dependent diabetes mellitus (IDDM)-susceptibility gene (IDDM13) has recently been mapped to a region of distal chromosome 2q, which is syntenic to the region of mouse chromosome 1 containing a murine susceptibility gene for IDDM, Idd5. To determine the contribution of this region to IDDM disease susceptibility further and to narrow the region for positional cloning of susceptibility genes, we have studied the association of distal chromosome 2q with IDDM in the genetically distinct Japanese population. A 137 mobility unit (mu) allele at D2S137 locus was significantly associated with IDDM (odds ratio 1.92, p = 0.0016). Other markers, D2S301 and D2S143, located in the same region were not associated with IDDM, indicating that IDDM13 is in linkage disequilibrium with D2S137, but not with D2S301 or D2S143. The association of D2S137 with IDDM was observed in patients lacking one of two high risk HLA alleles, DQB1 * 0303 and DQB1 * 0401, but not in patients with either of these alleles. The frequency of high risk HLA alleles was significantly lower in patients with the susceptible allele at D2S137, suggesting that IDDM13 contributes to IDDM susceptibility in subjects without high risk genotypes at IDDM1. Demonstration of allelic association of D2S137 with IDDM localizes IDDM13 in the close vicinity (〈 2 centiMorgans) of D2S137, greatly facilitating fine structure mapping and positional cloning of IDDM13. [Diabetologia (1998) 41: 228–232]
    Type of Medium: Electronic Resource
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  • 13
    ISSN: 1432-0428
    Keywords: Keywords Insulin sensitiser ; isoxazolidinedione ; JTT-501 ; GLUT4 ; phosphatidylinositol 3-kinase ; high fat diet ; adipocyte.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary JTT-501 is an insulin-sensitising compound with an isoxazolidinedione rather than a thiazolidionedione structure. Sprague-Dawley rats fed a high fat diet for 2 weeks were used as an animal model of insulin resistance, and JTT-501 was administered for the final week of the diet. An euglycaemic glucose clamp study showed that the glucose infusion rate (GIR) required to maintain euglycaemia was 57 % lower in rats fed a high fat diet than in control rats, and that JTT-501 treatment restored the reduction in GIR produced by the high fat diet. To explain the mechanisms underlying the effects of a high fat diet and JTT-501 treatment, epididymal fat pads were excised and used in the analysis of insulin action. The high fat diet caused: (1) a 58 % decrease in insulin receptor substrate-1 (IRS-1) content with a 58 % decrease in IRS-1 tyrosine phosphorylation; (2) reductions of 56 % and 73 % respectively in insulin-induced maximal PI 3-kinase activation in anti-phosphotyrosine and anti-IRS-1 antibody immunoprecipitates; (3) a 46 % reduction in the glucose transporter protein, GLUT4 content and, consequently, (4) severely impaired insulin-induced GLUT4 translocation to the plasma membrane and glucose uptake in adipocytes. JTT-501 treatment restored appreciably the protein content and tyrosine phosphorylation level of IRS-1. Insulin-stimulated PI 3-kinase activation was also restored in anti-phosphotyrosine and anti-IRS-1 antibody immunoprecipitates. As reflected by these improvements in insulin signalling, JTT-501 treatment improved considerably insulin-induced GLUT4 translocation to the plasma membrane as well as insulin-induced glucose uptake. However, JTT-501 had no effect on the decrease in GLUT4 content produced by the high fat diet. These observations suggest that JTT-501 enhances insulin signalling and may be effective in reducing insulin resistance. [Diabetologia (1998) 41: 400–409]
    Type of Medium: Electronic Resource
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  • 14
    ISSN: 1432-0428
    Keywords: Keywords NSY mouse, ageing, animal model, insulin resistance, glucose transporter 4.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The Nagoya-Shibata-Yasuda (NSY) mouse closely mimics human Type II (non-insulin-dependent) diabetes mellitus in that the onset is age-dependent, the animals are not severely obese, and both insulin resistance and impaired insulin response to glucose contribute to disease development. The aim of this study was to clarify the influence of age on the pathogenesis of diabetes and to analyse a candidate gene for Type II diabetes in this strain.¶Methods. Several phenotypic characteristics related to diabetes mellitus were monitored longitudinally in male NSY and control C3H/He mice. The nucleotide sequence of Glut4, a candidate gene for Nidd1nsy (a susceptibility gene for Type II diabetes) on Chromosome 11, encoding insulin-sensitive glucose transporter, was determined in NSY and C3H mice.¶Results. Glucose intolerance worsened with age, and fasting blood glucose and fasting plasma insulin concentration increased with age in NSY mice. Pancreatic insulin content increased until 24 weeks of age but then decreased at 48 weeks of age in NSY mice. The hypoglycaemic response to insulin was statistically significantly smaller in NSY than in C3H/He mice. The nucleotide sequence of GLUT4 cDNA was identical in NSY and C3H/He mice, but both were different from the sequence reported previously.¶Conclusion/interpretation. Insulin secretion and insulin resistance, as well as ageing possibly play an important part in the disease development in NSY mice. A decline of pancreatic insulin content in older age might cause the relative insulin deficiency in this strain. Nucleotide sequencing suggests that Glut4 is unlikely to be a candidate gene for Nidd1nsy. [Diabetologia (2000) 43: 932–938]
    Type of Medium: Electronic Resource
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  • 15
    ISSN: 1432-1041
    Keywords: angiotensin II analogues ; angiotensin II receptors ; 1-sarcosine ; 8-threonine angiotensin II ; 1-sarcosine ; 8-isoleucine angiotensin II ; 1-sarcosine ; 8-alanine angiotensin II ; blood pressure ; plasma aldosterone concentration ; plasma renin activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The biological effects of 1-Sarcosine, 8-Threonine angiotensin II ([Sar1, Thr8]ANG II) on blood pressure, plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were investigated in six normal subjects on an unrestricted diet, and compared with those of 1-Sarcosine, 8-Isoleucine ANG II ([Sar1, Ile8]ANG II) and 1-Sarcosine, 8-Alanine ANG II ([Sar1, Ala8]ANG II). All three ANG II analogues (A II A) showed agonistic pressor activity, that of [Sar1, Ile8]ANG II being greater than that of [Sar1, Thr8]ANG II or [Sar1, Ala8]ANG II. The antagonistic effect of [Sar1, Thr8]ANG II on blood pressure was less than [Sar1, Ile8]ANG II or [Sar1, Ala8]ANG II. Both [Sar1, Ile8]ANG II and [Sar1, Ala8]ANG II increased PAC and blocked the steroidogenic action of ANG II, while [Sar1, Thr8]ANG II showed little effect on PAC. All three A II A caused similar suppression of PRA and showed no inhibitory effect on the decrease in PRA produced by ANG II. These results indicate that [Sar1, Thr8] ANG II is an A II A with weak agonistic pressor action and that it has vascular selective properties. It is also suggested that ANG II receptors in a variety of target organs are heterogeneous.
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 329-332 
    ISSN: 1432-1041
    Keywords: reserpine ; hydrochlorothiazide ; pituitary hormones ; gonadal hormones ; hypertension ; serum concentration ; antihypertensive therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sex histories and serum samples were obtained from 27 hypertensive men before and after 3 months of therapy with either 100 mg of hydrochlorothiazide or 0.25 mg of reserpine daily. Sera were analyzed for testosterone, dihydrotestosterone, estradiol, luteinizing hormone and prolactin. Both drugs effectively lowered blood pressure. The incidence of impaired sexual performance was low and insignificantly different in the two treatment groups. There were no significant changes in serum hormone concentrations as a result of drug therapy.
    Type of Medium: Electronic Resource
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  • 17
    ISSN: 1432-1041
    Keywords: angiotensin II analogues ; aldosterone ; 1-sarcosine ; 8-isoleucine angiotensin II ; 1-sarcosine ; 8-alanine angiotensin II ; blood pressure ; dietics sodium ; plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Two angiotensin II analogues (AIIA), 1-sarcosine, 8-isoleucine angiotensin II ([Sar1, Ile8]-AII) and 1-sarcosine, 8-alanine angiotensin II ([Sar1, Ala8-AII), were infused in six normal volunteers on high, regular and low sodium diets. The agonist and antagonist activities of these AIIA on blood pressure (BP), plasma aldosterone concentration (PAC), creatinine clearance and plasma renin activity were examined. Both AIIA had agonistic pressor activities in subjects on high and regular sodium diets, [Sar1, Ile8]-AII being more potent than [Sar1, Ala8]-AII. Both AIIA caused similar elevation of PAC in subjects on high and regular sodium diets, and an equally fall in PAC in subjects on a low sodium diet. Both AIIA strongly antagonized the rise in BP, the increase in PAC and the reduction of Ccr induced by AII administration in subjects on all three sodium diets. The results indicate that both AIIA can be used to examine the activity of the renin-angiotensin system in patients with hypertension, and they also suggest that AII interaction with its receptors differs in different target tissues.
    Type of Medium: Electronic Resource
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  • 18
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 898 (1987), S. 231-238 
    ISSN: 0005-2736
    Keywords: Liposome ; Optical birefringence ; Phosphatidylcholine ; Pretransition
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 19
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 104 (1982), S. 280-284 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 20
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 123 (1984), S. 452-457 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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