Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q9UID3 (FFR)
 233 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to examine the role of muscle fiber composition in insulin resistance and the effect of a calcium channel antagonist on insulin sensitivity in fructose-induced insulin resistant and hypertensive rats. Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or fructose-rich diet (FFR). For the last 2 weeks of a 6-week period of either diet, the rats were treated, by gavage, with gum arabic solution (control or FFR) or a dihydropyridine calcium channel antagonist, benidipine hydrochloride (3 mg/kg/day: FFR + Ca), then the euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity. Blood pressure was measured weekly for 6 weeks. At the end of the glucose clamp, the soleus muscle was dissected out for determination of muscle fiber composition by ATPase methods. Blood pressure was elevated at 2 weeks after the start of fructose-rich chow feeding and persisted thereafter throughout the study. Blood pressure at the glucose clamp in the FFR was significantly higher than that in the control group (142 +/- 2 v 155 +/- 2 mm Hg, P < .01) and the calcium antagonist significantly lowered blood pressure of FFR (136 +/- 6 mm Hg for FFR +/- Ca, P < .05). The average rate of glucose infusion during glucose clamp, as a measure of insulin sensitivity (M value), was significantly lower in the FFR than in the control (15.4 +/- 0.4 v 10.9 +/- 0.6 mg/kg/min, P < .01). The calcium channel antagonist partially improved the M value compared to that of FFR (13.4 +/- 0.7 mg/kg/min in FFR +/- Ca, P < .01 compared to FFR, P < .05 compared to control). The composite ratio of type I fiber in soleus muscle was significantly decreased in FFR compared to control (81.7 +/- 1.5% v 75.0 +/- 1.7%, P < .01), and the composite ratio of type I fiber in rats treated with the calcium channel antagonist (FFR +/- Ca) recovered to the control level (79.9 +/- 1.1%, P < .05 compared to FFR). The M value was significantly correlated with the compositions of type I and type II fibers (for type I fibers, r = 0.80, P < .01; for type II fibers, r = -0.81, P < .01). These results suggest that fiber composition of skeletal muscle links insulin resistance and that a calcium channel antagonist may modulate muscle fiber composition in hypertensive animal model, fructose-fed rats.
 ...
PMID:Alteration of muscle fiber composition linking to insulin resistance and hypertension in fructose-fed rats. 1037 69

The aim of this study was to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor (AT) antagonist on insulin resistance, especially on muscle fiber composition in fructose-induced insulin-resistant and hypertensive rats. Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or a fructose-rich diet (FFR). For the last two weeks of a six-week period of either diet, the rats were treated with gum arabic solution as a vehicle (control or FFR), angiotensin-converting enzyme inhibitor (FFR+ACE), temocapril (1 mg/kg/ day) or an angiotensin II receptor antagonist (FFR+AT), CS-866 (0.3 mg/kg/day), by gavage, and then the euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity. At the end of the glucose clamp, the soleus muscle was dissected for determination of the muscle fiber composition by ATPase methods. Blood pressure at the glucose clamp in the FFR group was significantly higher than that of the control group, and both temocapril and CS-866 significantly lowered the blood pressure of the FFR group. The average rate of glucose infusion during the glucose clamp, as a measure of insulin sensitivity (M value), was significantly lower in the FFR rats compared to the controls (15.4 +/- 0.4, 10.9 +/- 0.6 mg/kg/min, for control and FFR, respectively, P < .01). Both temocapril and CS-866 partially improved the M values compared to FFR (13.2 +/- 0.7, 12.8 +/- 0.5 mg/kg/min, for FFR+ACE, FFR+AT, respectively, P < .01 compared with FFR, P < .05 compared with control). The composite ratio of type I fibers of the soleus muscle was decreased significantly in the FFR rats compared with the controls (82% +/- 2%, 75% +/- 2%, for control and FFR, respectively, P < .01), and both temocapril and CS-866 restored a composite ratio of type I fibers to the same level as that of the controls (81% +/- 1%, 80% +/- 1% for FFR+ACE and FFR+AT, respectively). The M value was significantly correlated with the composition of type I and type II fibers. These results suggest that the fiber composition of skeletal muscle is correlated to insulin resistance, and that both ACE inhibitors and AT antagonists may modulate the muscle fiber composition in a hypertensive and insulin-resistant animal model, fructose-fed rats, to the same extent.
 ...
PMID:The effects of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist on insulin resistance in fructose-fed rats. 1077 34

The normally positive force- and Ca2+ -frequency responses (FFR and CaFR) are inverted in heart failure (HF); whether oxidative stress contributes to these abnormalities is unknown. We evaluated the impact of acute and prolonged oxidative stress on contraction and Ca2+ handling in adult rat cardiomyocytes. Acute (30 min) exposure to H2O2 (100 microM) induced a twofold increase (P<0.025) in intracellular oxyradicals together with contractile depression despite preservation of the Ca2+ transient and the FFR and CaFR to 3 Hz, indicating reduced myofilament Ca2+ responsiveness. In contrast, prolonged (24 h) exposure to the copper-zinc superoxide dismutase inhibitor diethyldithiocarbamic acid (DDC, 1 microM) similarly augmented oxyradicals but also increased cell size, and contraction and Ca2+ transient duration (P<0.025). DDC-treated myocytes displayed inverted FFRs and attenuated (though still positive) CaFRs as compared to control, indicating reduced myofilament Ca2+ responsiveness coupled with altered Ca2+ handling. Protein levels of the Na+ -Ca2+ exchanger (NCX), sarcoplasmic reticular (SR) Ca2+ ATPase (SERCA2), and serine-16 phosphorylated phospholamban (pSer16-PLB) were increased (P<0.025), whereas dihydropyridine receptor abundance was decreased. Total PLB and ryanodine receptor protein expression were unchanged. Caffeine-induced Ca2+ release showed increased NCX activity (P<0.025) without changes in total releasable SR Ca2+, suggesting compensatory changes in SERCA2 and pSer16-PLB to maintain SR Ca2+ load. The superoxide scavenger Tiron attenuated these effects. Thus, acute oxyradical exposure rapidly depresses myofibrillar Ca2+ responsiveness. Prolonged oxidative stress further induces alterations in Ca2+ handling that combined with extant reductions in myofibrillar responsiveness invert the FFR. With regard to Ca2+ handling, reduced transsarcolemmal Ca2+ flux rather than reduced SR Ca2+ uptake was the primary determinant of a negative FFR. Analogous changes may be operative in HF, a state characterized by both oxidative stress and Ca2+ dysregulation.
 ...
PMID:Prolonged oxidative stress inverts the cardiac force-frequency relation: role of altered calcium handling and myofilament calcium responsiveness. 1628 76