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Biomedical subjects

Nobuyuki Ura

Publications and source records attributed to Nobuyuki Ura.

At least 37 records · Page 2Linked to original sources
PubMed2004

Blockade of the renin-angiotensin system decreases adipocyte size with improvement in insulin sensitivity.

OBJECTIVE: Based on results of in vitro studies, it has been hypothesized that blockade of the renin-angiotensin system (RAS) promotes the recruitment and differentiation of pre-adipocytes and that increased formation of small insulin-sensitive adipocytes counteracts ectopic deposition of lipids, thereby improving insulin sensitivity. We investigated the effect of RAS blockade on insulin sensitivity, adipocyte size, and intramuscular lipid content in fructose-fed rats (FFR) as a model of insulin-resistant hypertension. DESIGN AND METHODS: Six-week-old male Sprague-Dawley rats were divided into two groups: those fed a standard chow (control) and those fed a fructose-rich chow for 6 weeks. FFR were treated with a vehicle or with 1 mg/kg per day of temocapril, an angiotensin-converting enzyme inhibitor, or 0.1 mg/kg per day of olmesartan, an angiotensin II type 1 receptor blocker, for the last 2 weeks. Insulin sensitivity (M value: mg/kg per min) was estimated by the euglycemic hyperinsulinemic glucose clamp method. Sizes of adipocytes derived from epididymal fat and triglyceride content in the soleus muscle were determined. RESULTS: FFR had lower M value, higher blood pressure, larger adipocyte size, higher ratio of epididymal fat pads over body weight (%fat pads), and higher intramuscular triglyceride than did the control rats. Both temocapril and olmesartan significantly improved the M value and decreased blood pressure and adipocyte size without change in %fat pads in FFR. Adipocyte size was negatively correlated with the M value. Treatment for 2 weeks decreased, but not significantly, intramuscular triglyceride. CONCLUSIONS: RAS blockade decreases adipocyte size without change in epididymal %fat pads accompanied by improvement in insulin sensitivity.

Adipocytes↗
PubMed2004

Correlations of adiponectin level with insulin resistance and atherosclerosis in Japanese male populations.

OBJECTIVE: Adiponectin, which is secreted specifically by adipose tissue, has been shown to have an anti-atherosclerotic effect and to improve insulin resistance. The aim of this study was to determine the correlations of plasma adiponectin concentration with insulin resistance and atherosclerosis. DESIGN AND METHODS: We investigated the relationships of adiponectin concentration with insulin sensitivity, high-sensitivity C-reactive protein (hCRP) and pulse wave velocity (PWV) in male inhabitants of rural communities in Japan. hCRP and PWV were used as an indexes of atherosclerosis. RESULTS: A negative correlation was found between homeostasis model assessment (HOMA) as an index of insulin resistance and adiponectin concentration. Results of stepwise regression analysis for adiponectin showed that age, HOMA and serum triglyceride (TG) were independently correlated with adiponectin. Multiple regression analysis for lipid profile was also performed and revealed that adiponectin and HOMA were independently correlated with TG and serum high density lipoprotein (HDL)-cholesterol but not with serum total cholesterol. A significant negative correlation was found between adiponectin and hCRP in all subjects, and a significant negative correlation between adiponectin and PWV was also found in subjects equal or less than 70 years old. When HOMA was added to this analysis, HOMA was found to be independently correlated with hCRP and PWV, but the adiponectin level did not appear to be a significant predictor of hCRP or PWV. CONCLUSIONS: The results suggest that adiponectin plays a role in lipid metabolism and correlates with atherosclerosis either directly or through insulin resistance.

Adiponectin↗
PubMed2004

Granulocyte colony stimulating factor/macrophage colony stimulating factor improves postinfarct ventricular function by suppression of border zone remodelling in rats.

1. The aim of the present study was to examine the effects of mobilization of bone marrow cells by granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF) on ventricular function after myocardial infarction (MI). 2. After ligation of the left coronary artery, rats were divided into a vehicle control group (MI group) and a CSF-treated group (MI-CSF group). Rats in the MI-CSF group received a combination of G-CSF (50 microg/kg per day) and M-CSF (10(6) IU/kg per day) for 5 days after MI. Two weeks after MI, hearts were isolated and perfused with a Krebs' buffer and their functional responses to step-wise elevation of left ventricular end-diastolic pressure (LVEDP) were assessed. In histological analysis, proliferating cells and bone marrow-derived cells were identified by antibodies against Ki-67 and c-kit and organization of collagen was examined by picrosirius red staining. The mRNA levels of transforming growth factor (TGF)-beta(1), collagen type I and collagen type III were measured by quantitative reverse transcription-polymerase chain reaction. 3. Numbers of Ki-67- and c-kit-positive cells in the infarct border zone after MI were increased by CSF treatment, but few of those cells were stained by anti-alpha-sarcomeric actin. The levels in mRNA of TGF-beta1 and collagen type I in the infarct border zone were higher in the CSF-treated group compared with the MI group. Although CSF treatment did not reduce ventricular hypertrophy or infarct size at 2 weeks after MI, it did significantly improved the response of left ventricular developed pressure to step-wise elevation of LVEDP. This effect was mimicked by treatment with M-CSF alone. The functional improvement by CSF treatment was correlated with suppression of enlargement of the infarct-non-infarct border associated with infarct expansion. Collagen fibres in the border zone were thicker and orientated more orderly in the CSF-treated group than in the untreated group. 4. The results suggest that G-CSF/M-CSF treatment improves contractile function of the ventricle after infarction, presumably by acceleration of infarct repair and suppression of remodelling in the border zone.

Animals↗
PubMed2004

Angiotensin II receptor blocker prevents increased arterial stiffness in patients with essential hypertension.

BACKGROUND: High pulse wave velocity (PWV) is related to cardiovascular risk in essential hypertension (EHT). It is reported that short-term treatment with an angiotensin II receptor blocker (ARB) decreases PWV, as well as blood pressure (BP), and increases the serum adiponectin, known as an adipocytokine, which has an anti-atherosclerotic effect. However, it is not known whether long-term treatment with ARB prevents the increase in PWV independently of the reduction of BP, and whether adiponectin is related to the chronic effect of ARB on PWV. METHODS AND RESULTS: In order to examine the short-term effect of ARB on PWV, 9 subjects with EHT had PWV measured before and after treatment with an ARB for 1 month. The treatment significantly reduced PWV and BP. For evaluation of the long-term effect of ARB therapy, 56 consecutive subjects with EHT who were already taking anti-hypertensive drugs other than an angiotensin-converting enzyme inhibitor had their PWV measured. We divided the EHT subjects into 2 groups: (1) the ARB group (EHT treated with an ARB for at least 6 months) and (2) the control group (EHT treated with anti-hypertensive drugs other than an ARB). Although there was no significant difference between the 2 groups in BP, age or body mass index, the PWV value in the ARB group was significantly lower than that in the control group. Moreover, the serum adiponectin concentration in the ARB group was significantly higher than that in the control group. CONCLUSIONS: Long-term treatment with ARB inhibits the progression of arterial stiffness independent of BP reduction. One of the mechanisms may be related to the increased serum adiponectin concentration after treatment with an ARB.

Adiponectin↗
PubMed2004

Utility of serum ratio of heart-type fatty acid-binding protein to myoglobin for cardiac damage regardless of renal dysfunction.

BACKGROUND: The serum ratio of heart-type fatty acid-binding protein to myoglobin (F/M) has been shown to be a new marker for cardiac damage and volume overload in hemodialysis patients. We evaluated the utility of F/M in hemodialysis patients compared to control subjects. METHODS AND RESULTS: Twenty-one hemodialysis patients and 17 control subjects with normal renal function were investigated. Using a cutoff point of mean + 2SD of the F/M in the controls (value: 0.147), the hemodialysis patients were divided into 2 groups. The concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide after hemodialysis in the high F/M group were higher than those in the low F/M group. The mean level of ANP in the low F/M group was almost the upper limit of normal range. The values of left ventricular end-diastolic dimension and left ventricular mass index in the high F/M group were higher than those in the low F/M group, and the mean levels of those in the low F/M group were almost the same as those in the controls. CONCLUSIONS: The F/M can be evaluated by the absolute value regardless of renal dysfunction, and the value of 0.147 might be useful for determining the cutoff level of cardiac involvement.

Aged↗
PubMed2004

Renal protective role of bradykinin B1 receptor in stroke-prone spontaneously hypertensive rats.

The kallikrein-kinin system plays important roles in blood pressure regulation, metabolism of electrolytes and organ protection. Although the bradykinin B2 receptor (B2R) has been reported to be involved in most of these effects, a role of the bradykinin B1 receptor (B1R) has also been noted recently. The aim of this study was to determine the role of renal B1R in stroke-prone spontaneously hypertensive rats (SHR-SP). Sixteen-week-old SHR-SP and Wistar Kyoto rats (WKY) as a control were used in the experiments. A high level of B1R mRNA was detected in SHR-SP, while the expression in WKY was almost undetectable. Immunohistochemistry revealed a B1R protein in the renal tubules and glomeruli in SHR-SP. The acute injection of a B1 R agonist into SHR-SP increased urinary NOx excretion to a level up to 5-fold higher than that in the SHR-SP treated with vehicle. The infusion of B1 R antagonist for 4 weeks resulted in a significant elevation of blood pressure and urinary albumin excretion and a decrease in urinary NOx excretion in SHR-SP. The administration of B1 R antagonist resulted in renal interstitial and glomerular fibrosis in SHR-SP. Moreover, the expressions of transforming growth factor (TGF) beta1 protein and collagen III mRNA in SHR-SP treated with B1R antagonist were significantly higher than those of SHR-SP treated with a vehicle. The expression and phosphorylation of extracellular signal-regulated protein kinase (ERK) and p38, but not c-Jun N-terminal kinase (JNK), were significantly increased in the SHR-SP treated with B1R antagonist. These results indicated that renal B1R might be over-expressed in a high blood pressure condition, and that this upregulated B1 R may play an important role in renal protection by inhibiting renal fibrosis via an increase of NO production and a suppression of TGFbeta1 expression and mitogen-activated protein kinase (ERK and p38) phosphorylation.

Animals↗
PubMed2004

The role of renal natriuretic and depressor systems in insulin-resistant hypertensive rats.

Insulin resistance and impairment of the renal depressor system have been thought to be involved in the development of essential hypertension. However, the relationship between insulin resistance and this system is still unclear. To clarify this relationship, we investigated the role of the renal depressor system in a rat model of insulin-resistant hypertension. Sprague-Dawley rats were fed a standard diet (control) or a fructose-rich diet (FFR), and their blood pressures were measured every week. Urinary dopamine (uDA), urinary kallikrein (uKAL) activity and urinary nitric oxide (uNOx) levels were also measured each week, and the renal mRNA expression levels of endothelial nitric oxide synthase (eNOS), aromatic-L-amino-acid decarboxylase (AADC), and kallikrein (KAL) activity were compared at the end of the study. The blood pressure of FFR was elevated significantly from 2 weeks after the start of fructose loading. The uDA level was lower in FFR than in control rats throughout the study period (p<0.01), and the expression level of AADC mRNA was enhanced in FFR (p<0.05). There was a tendency of negative correlation between uDA level and systolic blood pressure (SBP) (r=-0.49, p=0.056). uNOx level was lower in FFR throughout the study period (p<0.05), and the eNOS mRNA expression level in the kidney was lower in FFR than in control rats (p<0.05). There was a negative correlation between uNOx level and SBP (r=-0.68, p <0.01). On the other hand, there was no significant difference in the kallikrein-kinin system between FFR and control rats. In conclusion, impairment in functions of the renal dopamine and NO systems occur in FFR, and this impairment may be caused by insulin resistance and may contribute to the development of hypertension.

Animals↗
PubMed2004

Possible impairment of transcardiac utilization of adiponectin in patients with type 2 diabetes.

OBJECTIVE: Adiponectin, an adipocyte-derived protein, has been suggested to enhance insulin sensitivity and prevent atherosclerosis. Circulating adiponecin levels are reduced in states of insulin resistance such as type 2 diabetes. We examined transcardiac utilization of adiponectin in patients with and without type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 17 male type 2 diabetic patients and 17 male nondiabetic patients were investigated. Venous blood samples were taken to measure glucose and lipid variables. Blood samples for the measurement of adiponectin were collected simultaneously from the aortic root and coronary sinus. Angiographic semiquantitative stenosis score of coronary artery was also evaluated. RESULTS: The adiponectin levels in both the aortic root and coronary sinus in the diabetic patients were significantly lower than those in the nondiabetic patients. The adiponectin level was significantly lower in the coronary sinus than in the aortic root in the nondiabetic patients, but there was no significant difference between adiponectin levels in the aortic root and coronary sinus in the diabetic patients. The total stenosis score, as an index of severity of coronary artery stenosis, was significantly higher in the diabetic patients than in the nondiabetic patients. The stenosis score was correlated with the degree of transcardiac utilization of adiponectin from the aortic root to coronary sinus in the nondiabetic patients but not in the diabetic patients. CONCLUSIONS: Diabetic patients not only have a decreased adiponectin level in the basal state compared with nondiabetic patients but also have impaired utilization of adiponectin in the coronary artery and/or the heart, which may promote the development of atherosclerosis.

Adiponectin↗
PubMed2004

[Adiponectin levels and coronary risk factors in the elderly].

AIM: To determine the relationship between adiponectin level and coronary risk factors in men. METHODS: The subjects were 395 elderly men in two rural communities (Tanno, Sobetsu) in Japan. Blood pressure in the sitting position (SBP/DBP), after overnight fasting, plasma glucose level (FPG), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL) and serum adiponectin were measured. The subjects were divided into two adiponectin level groups, a high adiponectin level (> or = 7.94 microg/ml) group (H-Adipo group) and a normal adiponectin level (< 7.94 microg/ml) group (N-Adipo group), and into two age groups, 70 years of age or older (70 or older group) and less than 70 years of age (under 70 group). RESULTS: Adiponectin showed negative correlations with BMI, FPG, TC and TG and positive correlations with age, SBP and HDL. In multiple regression analysis using adiponectin as a dependent variable. BMI, SBP, FPG, TG and HDL were selected as independent variables. Age and HDL in the H-Adipo group were significantly higher than those in the N-Adipo group, and BMI, FPG, TC and TG in the H-Adipo group were significantly lower than those in the N-Adipo group. In the 70 or older group. SBP and adiponectin were significantly higher and BMI, DBP, FPG, TC and TG were significantly lower than those in the under 70 group. The mean number of total coronary risk factors in the 70 or older group (1.71) was significantly lower than that in the under 70 group (2.06). CONCLUSIONS: Coronary risk factors other than systolic blood pressure were significantly reduced in the older subjects.

Adiponectin↗
PubMed2004

[Significance of insulin resistance to atherosclerotic complications in essential hypertension].

Insulin resistance and compensatory hyperinsulinemia are recognized not only in type 2 diabetes mellitus(DM) but also in essential hypertension(EHT), hyperlipidemia and obesity; these are known as the components of metabolic syndrome and accumulation of these components increase risk of cardiovascular diseases(CVD). When coronary angiographic findings were evaluated in patients with coronary artery disease(CAD), the severity was higher in CAD with DM than that without DM. Even in CAD without DM, the severity of coronary angiographic findings was higher in CAD with insulin resistance than that without insulin resistance. When residents of rural communities in Japan were followed 8 years, the incidence of CVD was 3.5 times higher in subjects with insulin resistance than those without insulin resistance. One of the intracellular signal transduction of insulin receptor; MAP kinase may be concerned atherosclerotic mechanisms of insulin resistance. These findings suggest that insulin resistance is a significant background of atherosclerosis, and insulin resistance is one of the major facilitation factors of genesis and progression of CVD.

Animals↗
PubMed2003

Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension.

Adiponectin, an adipocyte-derived protein, has been suggested to play an important role in insulin sensitivity. We examined the association between insulin sensitivity (M value) evaluated by the euglycemic-hyperinsulinemic glucose clamp and adiponectin concentrations in 30 essential hypertensives (EHT) and 20 normotensives (NT) and investigated the effect of blockade of the renin-angiotensin system (RAS) on adiponectin concentrations. EHT were divided into 12 insulin-resistant EHT (EHT-R) and 18 non-insulin-resistant EHT (EHT-N) using mean-1 SD of the M value in NT. There were no intergroup differences in age, gender, and body mass index (BMI). EHT-R had significantly higher levels of insulin and triglyceride and lower levels of adiponectin than did NT and EHT-N. EHT-R had higher levels of free fatty acid and lower levels of high-density lipoprotein (HDL) cholesterol than did EHT-N. Adiponectin concentrations were positively correlated with M value and HDL cholesterol and negatively correlated with BMI, insulin, free fatty acid, and triglyceride but not with blood pressure. M value, BMI, and HDL cholesterol were independent determinants of adiponectin concentrations in multiple and stepwise regression analyses. Sixteen EHT were treated with an angiotensin-converting enzyme inhibitor (temocapril, 4 mg/d; n=9) or an angiotensin II receptor blocker (candesartan, 8 mg/d; n=7) for 2 weeks. Treatment with temocapril or candesartan significantly decreased blood pressure and increased M value and adiponectin concentrations but did not affect BMI and HDL cholesterol. These results suggest that hypoadiponectinemia is related to insulin resistance in essential hypertension and that RAS blockade increases adiponectin concentrations with improvement in insulin sensitivity.

Adiponectin↗
PubMed2003

Circulating resistin levels in essential hypertension.

OBJECTIVE: Resistin, a novel cysteine-rich protein secreted by adipocytes, has been proposed to serve as a link between obesity and insulin resistance in rodents, but this has remained controversial. Most of the data obtained in previous studies are restricted to mRNA levels in tissues. DESIGN AND PATIENTS: We examined the association between insulin resistance and circulating protein levels of resistin in 33 essential hypertensive patients (EHT) and 18 normotensive subjects (NT). Insulin sensitivity (M-value) was evaluated by the euglycaemic hyperinsulinaemic glucose clamp technique. RESULTS: Using a cutoff point of mean - 1 SD of the M-value in the NT, the EHT were divided into two groups: one group of 12 insulin-resistant patients (EHT-R) and one group of 21 noninsulin-resistant patients (EHT-N). There were no intergroup differences in age, gender, body mass index (BMI; range: 20.1-30.4 kg/m2), fasting glucose and total cholesterol. The EHT-R had significantly higher levels of fasting insulin and triglyceride than did the NT and the EHT-N. The EHT-R had higher levels of free fatty acid and lower levels of high-density lipoprotein cholesterol than did the EHT-N. The M-value was negatively correlated with fasting insulin, free fatty acid, and triglyceride. Circulating resistin levels were not significantly different among the three groups and were not correlated with the M-value, BMI, blood pressure, or lipid variables. CONCLUSIONS: Our results suggest that circulating resistin levels are not related to insulin resistance, at least in patients with essential hypertension, although disturbance of lipid metabolism may be associated with insulin resistance.

Blood Glucose↗
PubMed2003

Serum ratio of heart-type fatty acid-binding protein to myoglobin. A novel marker of cardiac damage and volume overload in hemodialysis patients.

BACKGROUND: The concentration of heart-type fatty acid-binding protein (hFABP), a promising novel marker for detection of acute or persistent myocardial damage, is significantly influenced by renal clearance and thus has limitations to its usefulness in patients with renal dysfunction. We evaluated whether the serum ratio of hFABP to myoglobin (F/M) might be a useful marker for assessing cardiac damage in hemodialysis patients. METHODS: Serum hFABP and myoglobin were measured, and the value of F/M was calculated in 21 hemodialysis patients. Cardiac markers (cardiac troponin T [cTnT], atrial natriuretic peptide [ANP], and brain natriuretic peptide [BNP]) and echocardiographic indices (left ventricular end-diastolic dimension [LVDd], left ventricular mass index [LVMI], and inferior vena cava [IVC] dimension) were examined and compared with hFABP, myoglobin, and F/M ratios. RESULTS: Serum hFABP and myoglobin levels were significantly elevated in hemodialysis patients and reduced by 30-40% during hemodialysis. The value of F/M after hemodialysis, but not the concentration of hFABP or myoglobin, had significant linear correlations with ANP, BNP, cTnT, LVDd, LVMI, and IVC. CONCLUSION: The value of F/M after hemodialysis, but not the concentration of hFABP itself, might be a newly useful marker for estimation of cardiac damage and volume overload in hemodialysis patients.

Adult↗
PubMed2003

Tissue-specific impairment of insulin signaling in vasculature and skeletal muscle of fructose-fed rats.

The relation between insulin resistance/hyperinsulinemia and cardiovascular diseases has attracted much attention. Insulin affects not only glucose metabolism, but also protein synthesis and cell growth. Insulin stimulates both the phosphatidylinositol 3-kinase (PI3-K) and mitogen-activated protein kinase (MAPK) pathways, but the relationship between cardiovascular disease and selective insulin signal pathways is unclear. We investigated the tissue specificity and intracellular signal transduction selectivity of insulin resistance in the vasculature and skeletal muscle of fructose-fed rats (FFR). Sprague-Dawley rats were fed either normal rat chow (control rats) or fructose-rich chow. Normal saline with or without 1,000 (microg/kg) insulin was injected, and then the thoracic aorta or soleus muscle was removed under anesthetization. Insulin-induced tyrosine phosphorylation of insulin receptor beta subunit (IRbeta) and insulin receptor substrate-1 (IRS-1) and tyrosine/threonine phosphorylation of p44/42 MAPK (ERK-1/2) were evaluated. There were no significant differences in the degree of phosphorylation of IRbeta or ERK-1/2 in the thoracic aorta or in the soleus muscle between FFR and controls. However, tyrosine phosphorylation of IRS-1 in the soleus muscle of FFR was significantly reduced to 80% (p<0.001) of that in controls. The results suggest that PI3-K pathway in skeletal muscle is selectively impaired in FFR, and this impairment may induce hyperinsulinemia, which in turn may stimulate the MAPK pathway and lead to atherosclerosis. Thus PI3-K pathway may be one of the factors underlying the onset of cardiovascular disease in patients with insulin resistance.

Animals↗
PubMed2003

The effect of tumor necrosis factor-alpha on tissue specificity and selectivity to insulin signaling.

Recent studies have indicated that tumor necrosis factor (TNF)-alpha plays a significant role in insulin resistance. It has been proposed that selective impairment of insulin signaling in glucose metabolism is related to the development of atherosclerosis, although the mechanisms are not clear. The aim of this study was to elucidate the effect of TNF-alpha on tissue specificity and selectivity to insulin signaling. L6 myotubes and rat aortic vascular smooth muscle cells (VSMC) were cultured. Cells were stimulated with insulin pretreated with or without TNF-alpha. The protein extracts were used for electrophoresis and immunoblotting studies to examine phosphorylation of insulin receptor (IR)-beta, insulin receptor substrate (IRS)-1 and extracellular signal-regulated kinase (ERK). IR-beta phosphorylation was not affected by TNF-alpha in L6 or in VSMC. TNF-alpha significantly (p<0.05) inhibited IRS-1 phosphorylation by insulin but had no effect on ERK in L6. TNF-alpha had no effect on either IRS-1 phosphorylation or ERK in VSMC. Insulin induced ERK phosphorylation in a dose-dependent manner in VSMC. These results suggests that TNF-alpha plays a significant role in the tissue specificity and signal selectivity of insulin resistance. The pathway related to glucose metabolism is selectively impaired by TNF-alpha in skeletal muscle, and this impairment may induce compensatory hyperinsulinemia, which in turn would stimulate the pathway related to the cell proliferation in vascular tissues and possibly enhance the progression of atherosclerosis.

Animals↗
PubMed2003

Chinese medicine, Jiang-Tang-Ke-Li, improves insulin resistance by modulating muscle fiber composition and muscle tumor necrosis factor-alpha in fructose-fed rats.

Insulin resistance and hyperinsulinemia are common findings in patients with essential hypertension. These impairments in glucose metabolism are commonly associated with diabetes mellitus, hypertension, and dyslipidemia, which are high risk factors of cardiovascular diseases, and recent evidence indicates that they may play a role in the development of coronary artery disease. The aim of this study was to determine the effect of Jiang-Tang-Ke-Li (JTKL), a traditional Chinese medicine used to treat diabetes mellitus in China, on insulin resistance and hypertension in fructose-fed rats (FFR). Systolic blood pressures in the FFR groups were significantly higher than that in the control group, although JTKL had no effect on systolic blood pressure for the last 2 weeks of treatment with the medicine. The average rate of glucose infusion during a glucose clamp, as an index of insulin sensitivity (M value), was significantly lower in the FFR than in the control rats, and treatment with JTKL for 2 weeks significantly increased the M value to that of the control. Treatment with Panax ginseng (PG), a component of JTKL, for 2 weeks also significantly increased the M value of FFR to the control level. The composite ratio of type I fibers in soleus muscle decreased significantly in the FFR compared to that in the control, and treatment with JTKL led to recovery of the composite ratio of type I fibers to the same level as that of the control group. The M value showed a significant positive correlation with the composite ratio of type I fibers and a significant negative correlation with the composite ratio of type II fibers. Tumor necrosis factor (TNF)-alpha levels were significantly higher in the soleus and extensor digitorum longus (EDL) muscles of the FFR than in those of the control rats. Treatment with JTKL for 2 weeks significantly lowered TNF-alpha levels to the control levels. M values showed a significant negative correlation with TNF-alpha in both the soleus and EDL muscles. The results suggest that the Chinese medicine JTKL, which contains PG as one of its valid components, improves insulin resistance by modulating muscle fiber composition and TNF-alpha in skeletal muscles in hypertensive and insulin-resistant FFR.

Animals↗