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  • 1
    Electronic Resource
    Electronic Resource
    Beneficial Effect Of T-1095, A Selective Inhibitor Of Renal Na+–Glucose Cotransporters, On Metabolic Index And Insulin Secretion In Spontaneously Diabetic Gk Rats (2002)
    Melbourne, Australia : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 29 (2002), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. To investigate the pharmacological effects of T-1095, this novel derivative of phlorizin was administered to GK rats for 8 weeks. T-1095 treatment significantly lowered plasma glucose and glycosylated haemoglobin (HbA1c) levels, but did not significantly affect bodyweight.2. T-1095 treatment did not affect 3.3 mmol/L glucose-induced insulin secretion in the isolated perfused pancreas of GK rats.3. The peak insulin release in T-1095-treated GK rats was significantly higher during the first phase than in untreated GK rats (3–4 min after beginning 16.7 mmol/L glucose perfusion). The total amount of insulin secreted during the first phase in T-1095-treated GK rats was significantly higher than in untreated GK rats (35.3 ± 1.4 vs 27.3 ± 2.5 ng in T-1095-treated compared with untreated rats, respectively).4. During the second phase, insulin release in T-1095-treated GK rats was somewhat higher than in untreated GK rats (7–30 min after beginning 16.7 mmol/L glucose perfusion). The total amount of insulin secreted during the second phase in T-1095-treated GK rats was significantly higher than in untreated GK rats (88.2 ± 6.1 vs 68.1 ± 5.7 ng, respectively).5. The total amount of insulin secreted during perfusion in T-1095-treated GK rats was significantly higher than in untreated GK rats (123.5 ± 7.3 vs 95.4 ± 7.7 ng, respectively).6. These data show that the metabolic indices, plasma glucose and HbA1c levels and insulin secretion are significantly improved by T-1095 treatment in GK rats, which are spontaneously diabetic rats, suggesting its usefulness as a novel oral therapeutic antidiabetic agent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1440-1681.2002.03671.x
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  • 2
    Electronic Resource
    Electronic Resource
    T393C polymorphism of GNAS1 associated with the autonomic nervous system in young, healthy Japanese subjects (2004)
    Oxford, UK : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 31 (2004), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. T393C polymorphism of the gene encoding the Gs-protein α-subunit (GNAS1) has been reported recently to be associated with hypertension in which dysfunctions of the autonomic nervous system (ANS) are closely involved. In the present study, the association of this polymorphism with ANS activity was investigated in young, healthy Japanese males.2. Four hundred and one subjects were genotyped for the T393C polymorphism of GNAS1 by polymerase chain reaction–restriction fragment length polymorphism. Autonomic nervous system activity during supine rest and when standing was assessed in 137 subjects by electrocardiogram R-R interval power spectral analysis.3. One hundred and fifty-four subjects (38.4%) were homozygous for the T allele (TT), 188 (46.9%) were heterozygous (TC) and 59 (14.7%) were homozygous for the C allele (CC). There were no significant differences as to genotype among the clinical characteristics investigated. In power spectral analysis of heart rate variability, the high-frequency component and parasympathetic nervous system (PNS) index during supine rest were significantly lower in TT and TC carriers than in CC carriers. Furthermore, the increase in heart rate and the responsiveness of sympathetic nervous system index and PNS index to postural change from supine rest to standing were significantly lower in TT and TC carriers than in CC carriers.4. These observations suggest that the GNAS1 T393C polymorphism is associated with ANS activity in youth, so that it may be useful as a genetic marker for future pathogenesis of hypertension. Follow-up studies are necessary to clarify the prevalence rates of hypertension among 393T allele carriers in the present study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.2004.04059.x
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  • 3
    Electronic Resource
    Electronic Resource
    Abnormality in fibre type distribution of soleus and plantaris muscles in non-obese diabetic Goto-Kakizaki rats (2002)
    Oxford, UK : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 29 (2002), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Fibre type distributions of the slow soleus and fast plantaris muscles were investigated in 5-, 9- and 20-week-old male Goto-Kakizaki (GK) rats, as an animal model of non-obese diabetes, and were compared with those of age-matched non-diabetic Wistar rats.2. Bodyweight and both soleus and plantaris muscle weights were lower in GK rats than in Wistar rats, regardless of age. In addition, both relative soleus and plantaris muscle weights per bodyweight were lower in GK rats than in Wistar rats, regardless of age.3. In the soleus muscle, a higher percentage of type I fibres and a lower percentage of type IIA fibres were observed in 5- and 9-week-old GK rats. In addition, there were no type IIA fibres in 20-week-old GK rats.4. In the plantaris muscle, there were no differences in fibre type distribution of 5-week-old GK rats. However, a higher percentage of type IIB fibres and a lower percentage of type I and type IIA fibres were observed in 9- and 20-week-old GK rats. In addition, there were no type I fibres in 20-week-old GK rats.5. These results indicate that the decreased percentage of high-oxidative fibres (e.g. type IIA fibres in the soleus muscle and type I and type IIA fibres in the plantaris muscle) of the diabetic animals is concerned with an impairment in insulin sensitivity and glucose metabolism and is not related to bodyweight.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1440-1681.2002.03757.x
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  • 4
    Electronic Resource
    Electronic Resource
    Inhibition of gastric inhibitory polypeptide signaling prevents obesity (2002)
    [s.l.] : Nature Publishing Group
    Nature medicine 8 (2002), S. 738-742 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat. Here we describe a novel pathway of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nm727
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