ABSTRACT
This study aimed to examine the effect of eicosapentaenoic acid (EPA) on skeletal muscle hypertrophy induced by muscle overload and the associated intracellular signaling pathways. Male C57BL/6J mice were randomly assigned to oral treatment with either EPA or corn oil for 6 weeks. After 4 weeks of treatment, the gastrocnemius muscle of the right hindlimb was surgically removed to overload the plantaris and soleus muscles for 1 or 2 weeks. We examined the effect of EPA on the signaling pathway associated with protein synthesis using the soleus muscles. According to our analysis of the compensatory muscle growth, EPA administration enhanced hypertrophy of the soleus muscle but not hypertrophy of the plantaris muscle. Nevertheless, EPA administration did not enhance the expression or phosphorylation of Akt, mechanistic target of rapamycin (mTOR), or S6 kinase (S6K) in the soleus muscle. In conclusion, EPA enhances skeletal muscle hypertrophy, which can be independent of changes in the AKT-mTOR-S6K pathway.
Subject(s)
Eicosapentaenoic Acid/therapeutic use , Hypertrophy/pathology , Muscle, Skeletal/drug effects , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism , Animals , Hypertrophy/chemically induced , Hypertrophy/metabolism , Male , Mice , Mice, Inbred C57BL , Models, Animal , Muscle, Skeletal/metabolism , Phosphorylation , Signal TransductionABSTRACT
OBJECTIVES: To assess the effects of 24 months training on muscle quality, size, strength, and gait abilities in older adults who need long-term care. DESIGN: Non-randomized controlled trial Setting: Kawai Rehabilitation Center and Kajinoki Medical Clinic. PARTICIPANTS: Ten older participants who needed long-term care (age, 76.7 ± 5.6 years) were participated as training group (Tr-group) and 10 older men and women who did not require long-term care (age, 72.9 ± 6.6 years) comprised the control group (Cont-group). INTERVENTION: Tr-group performed resistive and endurance exercises once or twice a week for 24 months. MEASUREMENTS: Using ultrasound images, echo intensity (EI) and muscle thickness were measured in the rectus femoris and biceps femoris as an index of muscle quality and size. Physical performance was measured before and after the training; performance parameters included knee extension peak torque, 5-m normal and maximal walk test, sit-to-stand and timed up and go test. RESULTS: After the training, there was no change in EI, while BF thickness was increased (pre; 1.82 ± 0.29 cm, 24 months; 2.14 ± 0.23 cm, p < 0.05) in Tr-group. Walk-related performances were improved after the training in Tr-group (i.e. 5-m walk test and timed up and go test). The percent change of knee extension peak torque explained the percent change of EI in the rectus femoris (regression coefficient = 1.24, R = 0.91, adjusted R2 = 0.82, p < 0.001). CONCLUSIONS: Twenty-four months' training induced muscle hypertrophy and improved physical functions. Increased muscle quality in the rectus femoris could be a key to improved knee extension peak torque, with the potential to eventually reduce the need for long-term care in older individuals.
Subject(s)
Endurance Training/methods , Muscle Strength/physiology , Muscle, Skeletal/physiology , Resistance Training/methods , Aged , Female , Humans , Long-Term Care , Male , Physical Endurance/physiology , Time FactorsABSTRACT
This study aimed to examine how regular aerobic training can affect the muscle hypertrophy induced by overloading. Male C57BL/6J mice were randomly divided into three groups: rest group, low-intensity aerobic exercise group, and high-intensity aerobic exercise group. Mice in the exercise groups were assigned to run at a speed of 10 m/min (low-intensity) or 25 m/min (high-intensity) for 30 min/day, five days/week, for four weeks. Then, the right hind leg gastrocnemius muscles were surgically removed to overload the plantaris and soleus muscles, while the left hind leg was subjected to a sham-operation. Both the plantaris and soleus muscles grew larger in the overloaded legs than those in the sham-operated legs. Muscle growth increased in the plantaris muscles in the low-intensity exercise group compared to that in the rest or high-intensity exercise groups at one and two weeks after overloading. This enhancement was not observed in the soleus muscles. Consistently, we observed changes in the expression of proteins involved in anabolic intracellular signaling, including Akt, mechanistic target of rapamycin (mTOR), and p70S6K, in the plantaris muscles. Our data showed for the first time that chronic low-intensity aerobic exercise precipitates overload-induced muscle growth.
Subject(s)
Adaptation, Physiological/physiology , Exercise Test/methods , Muscle Strength/physiology , Muscle, Skeletal/physiology , Physical Conditioning, Animal/physiology , Animals , Hypertrophy/physiopathology , Male , Mice , Mice, Inbred C57BL , Muscle Proteins/metabolism , Physical Conditioning, Animal/methodsABSTRACT
Luseogliflozin, a selective inhibitor of sodium glucose co-transporter 2 (SGLT2), was previously shown to improve the blood glucose and hemoglobin A1c (HbA1c) levels of patients with type 2 diabetes in a clinical setting. Although patients with type 2 diabetes often have hepatic impairment, few reports have been published concerning the influence of luseogliflozin on HbA1c and hepatic function in patients with type 2 diabetes accompanied by hepatic impairment. The present study was undertaken to evaluate the influence of luseogliflozin on HbA1c and hepatic function in patients with type 2 diabetes divided into 2 groups according to hepatic function parameters (a normal group and an elevated group). In this study, luseogliflozin significantly improved both HbA1c and body weight to similar extents in both the normal group and the elevated group, accompanied by marked reductions in the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (γ-GTP) levels. These results suggested that luseogliflozin can be safely used in patients with type 2 diabetes who also exhibit hepatic impairment. The results additionally suggest the possibility that luseogliflozin might be capable of alleviating hepatic impairment in patients with type 2 diabetes.
Subject(s)
Diabetes Mellitus, Type 2/complications , Liver Diseases/drug therapy , Liver Diseases/etiology , Sodium-Glucose Transporter 2 Inhibitors , Sorbitol/analogs & derivatives , Asian People , Blood Glucose/drug effects , Body Weight/drug effects , Diabetes Mellitus, Type 2/metabolism , Female , Glycated Hemoglobin/metabolism , Humans , Liver/drug effects , Liver/metabolism , Liver Diseases/metabolism , Liver Function Tests/methods , Male , Retrospective Studies , Sodium-Glucose Transporter 2 , Sorbitol/therapeutic useABSTRACT
It has been reported that dipeptidyl peptidase-4 (DPP-4) inhibitors improve hemoglobin A1c (HbA1c) levels in diabetic patients and may also improve the serum lipids. However, few studies have examined relationship between the effects of the DPP-4 inhibitor and the pretreatment HbA1c levels in diabetic patients. Furthermore, it has been reported that prolonged treatment with DPP-4 inhibitors may make glycemic control difficult in some patients. In the present study, we investigated (1) the effect of the DPP-4 inhibitor alogliptin on HbA1c, blood glucose (BG), and serum lipid in Japanese patients with type 2 diabetes, (2) the relationship between the HbA1c levels at baseline and the effects of alogliptin, and (3) the effects of switching of the DPP-4 inhibitor to alogliptin after 12 months' administration of sitagliptin on glycemic control and serum lipids. After 6-months' treatment with alogliptin, we found reductions of HbA1c, BG, and serum total cholesterol, and LDL cholesterol levels. Pretreatment level of HbA1c was well correlated with the degree of reduction of both HbA1c and BG levels after the treatment. Also, alogliptin kept levels of HbA1c and BG reduced by sitagliptin for 12 months, and relapsing of these levels and serum lipids were not observed. This study revealed that alogliptin improved HbA1c, BG, and serum lipid profiles in type 2 diabetic patients, and the effect of alogliptin on HbA1c and BG levels was correlated with HbA1c level at pretreatment. Furthermore, long-term treatment with alogliptin did not cause relapsing of glycemic control and serum lipids.
Subject(s)
Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Glycated Hemoglobin/metabolism , Lipids/blood , Piperidines/therapeutic use , Uracil/analogs & derivatives , Asian People , Blood Glucose/drug effects , Female , Humans , Hypoglycemic Agents/therapeutic use , Male , Middle Aged , Sitagliptin Phosphate/therapeutic use , Uracil/therapeutic useABSTRACT
Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to improve the glycemic control and blood hemoglobin A1c (HbA1c) concentrations. However, there are few reports as yet suggesting that DPP-4 inhibitors may also improve insulin resistance and the serum lipid profile in the clinical setting. This study was aimed at investigating the effect of 14-week treatment with teneligliptin (20 mg/day) on the homeostasis model assessment ratio (HOMA-R), an indicator of insulin resistance, and serum lipid profile in 9 patients with type 2 diabetes. The treatment produced a significant decrease of the blood glucose and HbA1c concentration (blood glucose: p=0.008; HbA1c: p=0.038), and also improved HOMA-R (p=0.039). Furthermore, the patients showed elevation of the serum HDL-cholesterol level (p=0.032), and a tendency towards reduction of the serum triglyceride level. The results indicate that teneligliptin acts not only to improve the blood glucose control, but also to improve the insulin resistance and serum lipid profile in Japanese type 2 diabetes patients.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Insulin Resistance , Lipids/blood , Pyrazoles/pharmacology , Thiazolidines/pharmacology , Aged , Asian People , Blood Glucose/drug effects , Diabetes Mellitus, Type 2/blood , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Female , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/pharmacology , Male , Middle Aged , Prospective Studies , Pyrazoles/therapeutic use , Thiazolidines/therapeutic use , Treatment OutcomeABSTRACT
In recent years, the number of patients with type 2 diabetes mellitus caused by insulin resistance has continued to increase in Japan. Insulin resistance is considered to be closely related to the risk of cardiovascular diseases and atherosclerotic diseases, represented by arteriosclerosis obliterans (ASO). Therefore, improvement of insulin resistance is one of the important strategies in the treatment of type 2 diabetes mellitus. At present, α-glucosidase inhibitors, incretin-related drugs, and thiazolidinediones are among the most important oral hypoglycemic drugs used to improve insulin resistance. In this study, the effect of beraprost sodium, a prostaglandin I2 derivative, in the treatment of type 2 diabetes mellitus was investigated. In type 2 diabetic patients with ASO who were under treatment with pioglitazone, additional treatment with beraprost sodium exerted a significant synergistic effect in reducing the serum HbA1c levels as compared to treatment with pioglitazone alone. This result indicates that concomitant administration of pioglitazone and beraprost sodium may be useful in the treatment of diabetes -mellitus.
Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Epoprostenol/analogs & derivatives , Hypoglycemic Agents/administration & dosage , Thiazolidinediones/administration & dosage , Aged , Drug Therapy, Combination , Epoprostenol/administration & dosage , Female , Humans , Male , Middle Aged , Pioglitazone , Platelet Aggregation InhibitorsABSTRACT
We aimed to determine whether acute treatment with candesartan cilexetil (CV-11974), an angiotensin II type 1 receptor blocker (ARB) can improve insulin sensitivity in high-fructose-diet (HFD)-fed rats. In vivo glucose utilization was measured by applying the euglycemic clamp technique and the expression levels of insulin-signaling molecules in skeletal muscles were examined by western blotting. A bolus injection of CV-11974 improved the glucose infusion rate (GIR) of HFD-fed rats to the level of the control rats. Furthermore, restoration of impaired tyrosine phosphorylation of insulin receptor (IR) ß, Akt phosphorylation at Ser47³ and Thr³°8, and phosphorylation of the 160-kDa Akt substrate (AS160) in the skeletal muscles of HFD-fed rats were achieved by this treatment. These results suggest that acute administration of candesartan cilexetil can increase insulin sensitivity of HFD-fed rats, which is associated with improved insulin signaling in skeletal muscles.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , Benzimidazoles/therapeutic use , Biphenyl Compounds/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Insulin Resistance , Tetrazoles/therapeutic use , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/metabolism , Disease Models, Animal , Fructose/metabolism , Humans , Male , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Rats , Rats, WistarABSTRACT
AIM: This study was designed to determine the type and amount of the monomers leached from the different particle sizes of the composite materials. MATERIALS AND METHODS: Three different disk sizes (2, 4, 6 mm) prepared for each material group (Filtek Flow, Filtek A110, Filtek P60 and Filtek Supreme) were polymerised by LED and halogen light; the specimens were then placed in artificial saliva. The monomer release in 30 min and 24 hrs from the specimens was analyzed in HPLC calibrated for the monomer extracts before. RESULTS: TEGDMA release was detected in all material groups after 30 min and after 24 hrs. BisGMA and BisEMA were not determined in any groups and UDMA was detected only in Filtek Supreme. Significant differences in release of TEGDMA and UDMA were obtained between the different sizes of discs. Significantly high amount of TEGDMA and UDMA monomer release was obtained in LED than Halogen groups. Lower amount of monomer release was obtained in species of 30 min than 24 hrs. CONCLUSION: Data has revealed that the monomer release could be detected significantly high from the composite materials polymerized by a lower output curing light device; and higher elution of monomers was determined as the composite thickness has increased. Therefore, the clinical applications of composite materials and the type of curing units have very important effects on the success of restorations and in the decrease of potential side effects.
Subject(s)
Composite Resins/chemistry , Light-Curing of Dental Adhesives , Methacrylates/analysis , Bisphenol A-Glycidyl Methacrylate/analysis , Chromatography, High Pressure Liquid , Curing Lights, Dental , Particle Size , Polyethylene Glycols/analysis , Polymerization , Polymethacrylic Acids/analysis , Polyurethanes/analysis , Saliva, Artificial , SemiconductorsABSTRACT
The present study examined the effect of combination of short-term calorie restriction (CR) and moderate exercise on insulin action in normal rats. Rats were divided randomly into 4 groups: ad libitum, sedentary (A-Sed); calorie restriction, sedentary (CR-Sed); ad libitum, exercise (A-Ex); and calorie restriction, exercise (CR-Ex). Rats in the exercise groups were run on a rodent treadmill. Rats in the CR groups were fed every alternate day. Oral glucose tolerance test (OGTT) showed improvements in both CR-Sed and A-Ex groups compared with the A-Sed group; no further improvement in glucose tolerance was observed in the CR-Ex group. In contrast, glucose infusion rates (GIRs) determined by the hyperinsulinemic-euglycemic clamp method indicated that the GIR of the CR and exercise combination was significantly better than that of the sole intervention of CR or exercise. There was no difference in the levels of fasting glucose, insulin, or high-molecular weight forms of adiponectin among the 4 groups. Protein expression of GLUT-4 in the skeletal muscle increased by exercise, but not by CR. Our findings indicate that the combination of exercise and CR may be effective in enhancing insulin sensitivity at the skeletal muscle in normal subjects.
Subject(s)
Caloric Restriction/methods , Insulin/pharmacology , Physical Conditioning, Animal/methods , Adiponectin/blood , Animals , Blood Glucose/metabolism , Body Weight/drug effects , Diet , Fasting/blood , Feeding Behavior/drug effects , Glucose Clamp Technique , Glucose Tolerance Test , Glucose Transporter Type 4/metabolism , Hyperinsulinism/blood , Infusion Pumps , Insulin/administration & dosage , Insulin/blood , Male , Molecular Weight , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Rats , Time FactorsABSTRACT
The molecular mechanism of insulin resistance induced by high-fructose feeding is not fully understood. The present study investigated the role of downstream signaling molecules of phosphatidylinositol 3-kinase (PI3K) in the insulin-stimulated skeletal muscle of high-fructose-fed rats. Rats were divided into chow-fed and fructose-fed groups. The results of the euglycemic clamp study (insulin infusion rates: 6 mU/kg BW/min) showed a significant decrease in the glucose infusion rate (GIR) and the metabolic clearance rate of glucose (MCR) in fructose-fed rats compared with chow-fed rats. In skeletal muscle removed immediately after the clamp procedure, high-fructose feeding did not alter protein levels of protein kinase B (PKB/Akt), protein kinase C zeta (PKCzeta), or glucose transporter 4 (GLUT4). However, insulin-stimulated phosphorylation of Akt and PKCzeta and GLUT4 translocation to the plasma membrane were reduced. Our findings suggest that insulin resistance in fructose-fed rats is associated with impaired Akt and PKCzeta activation and GLUT4 translocation in skeletal muscle.
Subject(s)
Diet/adverse effects , Fructose/adverse effects , Glucose Transporter Type 4/metabolism , Oncogene Protein v-akt/metabolism , Protein Kinase C/metabolism , Animals , Blood Glucose/metabolism , Blotting, Western , Glucose Clamp Technique , Insulin/physiology , Male , Muscle, Skeletal/enzymology , Muscle, Skeletal/metabolism , Phosphorylation , Protein Transport/physiology , Rats , Rats, Wistar , Signal Transduction/drug effects , Signal Transduction/physiologyABSTRACT
Stimulation of AMPK and decreased glycogen levels in skeletal muscle have a deep involvement in enhanced insulin action and GLUT-4 protein content after exercise training. The present study examined the chronic effects of a continuous low-carbohydrate diet after long-term exercise on GLUT-4 protein content, glycogen content, AMPK, and insulin signaling in skeletal muscle. Rats were divided randomly into four groups: normal chow diet sedentary (N-Sed), low carbohydrate diet sedentary (L-Sed), normal chow diet exercise (N-Ex), and low carbohydrate diet exercise (L-Ex) groups. Rats in the exercise groups (N-Ex and L-Ex) were exercised by swimming for 6 hours/day in two 3-hour bouts separated by 45 minutes of rest. The 10-day exercise training resulted in a significant increase in the GLUT-4 protein content (p<0.01). Additionally, the GLUT-4 protein content in L-Ex rats was increased by 29% above that in N-Ex rats (p<0.01). Finally, the glycogen content in skeletal muscle of L-Ex rats was decreased compared with that of N-Ex rats. Taken together, we suggest that the maintenance of glycogen depletion after exercise by continuous low carbohydrate diet results in the increment of the GLUT-4 protein content in skeletal muscle.
Subject(s)
Diet, Carbohydrate-Restricted , Glucose Transporter Type 4/metabolism , Muscle, Skeletal/metabolism , Physical Conditioning, Animal , AMP-Activated Protein Kinases , Adaptor Proteins, Signal Transducing/metabolism , Animals , Blood Glucose , Glycogen/metabolism , Insulin Receptor Substrate Proteins , Male , Multienzyme Complexes/metabolism , Muscle, Skeletal/enzymology , Phosphorylation , Protein Serine-Threonine Kinases/metabolism , Rats , Rats, Wistar , Time FactorsABSTRACT
BACKGROUND: A new approach called "minimum intervention" has been introduced for restoration of carious lesions to preserve tooth structure. This approach suggests that perhaps caries need not always be removed completely from deeper portions of the cavity. It is, therefore, important to characterize caries-affected dentin structures, because of the potential changes in bonding quality when using different dentinal substrates. MATERIALS AND METHOD: Ninety teeth (30 teeth each group) were studied. The first group (CF) consisted of 30 caries-free teeth. The second group (CC) consisted of 30 teeth, for which caries-free dentin teeth was chemically demineralized. The third group (ND) consisted of 30 extracted human molars with coronal carious lesions. After all tooth samples were water-polished with grit #600 SiC paper, they were tested by surface contact angle measurements and the electron-probe microanalyzer to measure Ca/P mol ratio. RESULTS: Contact angles were CF = 60.07 degrees ; CC = 30.8 degrees; ND = 26.11 degrees , p<0.05. Ca/P mol ratios were as follows; CF = 1.549 (+/-0.0435); CC = 1.324 (+/-0.2305); ND = 1.568 (+/-0.0523), p<0.05. Weibull analyses for Ca/P mol ratio indicated shape parameter (m) of CF was 13.3; it was 12.8 for ND and 11.8 for CC. Above the delta point (=1.65 in Ca/P ratio), for both groups m = 3.4. CONCLUSION: Caries-affected dentin surfaces (naturally-developed and chemically created) were statistically more chemically active than caries-free dentin surface. Ca/P mol ratio of chemically created caries was less than other two groups.
Subject(s)
Calcium/chemistry , Dental Caries/metabolism , Dentin/chemistry , Durapatite/chemistry , Phosphorus/chemistry , Tooth/chemistry , Calcium/analysis , Durapatite/analysis , Humans , In Vitro Techniques , Molecular Weight , Phosphorus/analysis , Surface PropertiesABSTRACT
BACKGROUND: When a dissimilar couple is exposed to corrosive environment, it will normally exhibit a galvanic corrosion. The galvanic corrosion might be influenced by various factors, including type and concentration of electrolyte, surface area ratio between anode and cathode, type of coupling material, and coupling manner. PURPOSE: The purpose of this study was to investigate and compare the galvanic corrosion behavior of commercially pure titanium when coupled with type IV Au alloy, Au-Ag-Pt alloy, and Ag-Au-Pd alloy by different coupling methods. MATERIALS AND METHODS: Couples were prepared by a laser welding or a mechanical adhering method. Electrochemical corrosion studies were conducted in a Ringer's solution at a scanning rate of 0.1 mV/sec in a range from -250 mV to +250 mV with respect to E(OCP). Corrosion parameters (E(OCP), I(CORR), E(CORR)) were obtained. RESULTS: It was found that (i) there was a significant difference between LWC and AJC for three couples (p<0.05), (ii) the crevice line caused all three couples more corrosive than weld joint line, (iii) for both joint, it was found that type (IV) Au alloy exhibited discoloration to some extent. CONCLUSIONS: It is concluded that among the three couples with two different coupling methods, Ti/Ag-Au-Pd couple exhibited best corrosion resistance in a room temperature Ringer's solution.
Subject(s)
Dental Alloys/chemistry , Electrochemistry/methods , Electrogalvanism, Intraoral , Titanium/chemistry , Corrosion , Dental Alloys/analysis , Electromagnetic Fields , Materials Testing , Surface Properties , Titanium/analysisABSTRACT
High-fat feeding diminishes insulin-stimulated glucose transport in skeletal muscle. However, conflicting results are reported regarding whether phosphatidylinositol (PI)-3 kinase-independent glucose transport is also impaired in insulin-resistant high-fat-fed rodents. The aim of the present study was to study whether non-insulin-dependent mechanisms for stimulation of glucose transport are defective in skeletal muscle from high-fat-fed rats. Rats were fed normal chow diet or high-fat diet for 4 weeks and isolated epitrochlearis muscles were used for measuring glucose transport. Insulin-stimulated glucose transport was significantly lower in rats fed the high-fat diet compared with chow-fed rats (P < .05). Hypoxia-stimulated glucose transport was also reduced in high-fat-fed rats (P < .05). Nevertheless, hypoxia-stimulated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation (Thr172) level was not affected by high-fat feeding. Glucose transport by sodium nitroprusside stimulation was reduced in high-fat-fed rats (P < .05). Protein content of glucose transporter (GLUT)-4 and AMPK-alpha, and glycogen content were comparable between both groups. Our findings provide evidence that high-fat feeding can affect not only insulin but also non-insulin-stimulated glucose transport. A putative defect in common steps in glucose transport may play a role to account for impaired insulin-stimulated glucose transport in rats fed a high-fat diet.
Subject(s)
Aminoimidazole Carboxamide/analogs & derivatives , Dietary Fats/pharmacology , Glucose/metabolism , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Muscle Proteins , Muscle, Skeletal/metabolism , Adenylate Kinase/metabolism , Aminoimidazole Carboxamide/pharmacology , Animals , Biological Transport, Active/drug effects , Blotting, Western , Glucose Transporter Type 4 , In Vitro Techniques , Male , Monosaccharide Transport Proteins/metabolism , Muscle, Skeletal/drug effects , Muscle, Skeletal/enzymology , Nitric Oxide Donors/pharmacology , Nitroprusside/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Rats , Rats, Wistar , Ribonucleotides/pharmacologyABSTRACT
The aim of this study was to determine whether cinnamon extract (CE) would improve the glucose utilization in normal male Wistar rats fed a high-fructose diet (HFD) for three weeks with or without CE added to the drinking water (300 mg/kg/day). In vivo glucose utilization was measured by the euglycemic clamp technique. Further analyses on the possible changes in insulin signaling occurring in skeletal muscle were performed afterwards by Western blotting. At 3 mU/kg/min insulin infusions, the decreased glucose infusion rate (GIR) in HFD-fed rats (60 % of controls, p < 0.01) was improved by CE administration to the same level of controls (normal chow diet) and the improving effect of CE on the GIR of HFD-fed rats was blocked by approximately 50 % by N-monometyl-L-arginine. The same tendency was found during the 30 mU/kg/min insulin infusions. There were no differences in skeletal muscle insulin receptor (IR)-beta, IR substrate (IRS)-1, or phosphatidylinositol (PI) 3-kinase protein content in any groups. However, the muscular insulin-stimulated IR-beta and IRS-1 tyrosine phosphorylation levels and IRS-1 associated with PI 3-kinase in HFD-fed rats were only 70 +/- 9 %, 76 +/- 5 %, and 72 +/- 6 % of controls (p < 0.05), respectively, and these decreases were significantly improved by CE treatment. These results suggest that early CE administration to HFD-fed rats would prevent the development of insulin resistance at least in part by enhancing insulin signaling and possibly via the NO pathway in skeletal muscle.
Subject(s)
Cinnamomum zeylanicum/chemistry , Fructose/administration & dosage , Insulin Resistance , Plant Extracts/pharmacology , Animals , Blood Glucose/analysis , Body Weight , Diet , Dose-Response Relationship, Drug , Eating , Fatty Acids, Nonesterified/blood , Glucose/administration & dosage , Glucose/metabolism , Glucose Clamp Technique , Insulin/blood , Insulin Receptor Substrate Proteins , Male , Phosphoproteins , Phosphorylation/drug effects , Rats , Rats, Wistar , Receptor, Insulin/metabolism , Tyrosine/metabolismABSTRACT
Studies of C-peptide cellular effects show that not only the full-length native peptide but also specific C-terminal fragments are biologically active in in vitro systems. In the present study, the effect of five C-peptide fragments and the native peptide on whole-body glucose turnover was studied in streptozotocin diabetic rats using the insulin clamp technique. Insulin was infused intravenously at 18 pmol kg(-1) min(-1) for 90 min and blood glucose concentration was clamped at 8 and 4 mM in diabetic and non-diabetic animals. A steady state was reached during the last 30 min of the study period. Rat C-peptide II and fragments comprising residues 27-31 and 28-31 were effective in augmenting glucose turnover in diabetic rats (+100% to 150%), while no significant effects were seen for segments 1-26, 11-19 and 11-15. The metabolic clearance rate for glucose during infusion of C-peptide or fragments 27-31 and 28-31 in diabetic rats was similar to that seen in non-diabetic animals. We conclude that C-terminal tetra- and pentapeptides, but not fragments from the middle segment of C-peptide, are as effective as the full-length peptide in stimulating whole-body glucose turnover in diabetic rats.
Subject(s)
Blood Glucose/metabolism , C-Peptide/administration & dosage , Diabetes Mellitus, Experimental/metabolism , Animals , Body Weight , Glucose Clamp Technique , Infusions, Intravenous , Insulin/administration & dosage , Male , Metabolic Clearance Rate , Peptide Fragments/administration & dosage , Rats , Rats, WistarABSTRACT
We have studied the effect of imidapril, an angiotensin-converting enzyme inhibitor, on streptozotocin-induced diabetic rats. A sequential euglycemic hyperinsulinemic clamp procedure was used (insulin infusion rates: 3 and 30 mU/kg BW/min) in 30 diabetic rats. The rats were divided in 6 groups: a control group, a control group with N-monomethyl-L-arginine (L-NMMA, 1 mg/kg/min, a nitric oxide synthase inhibitor) infusion, a streptozotocin-induced diabetic group, a diabetic group with L-NMMA infusion, a diabetic group involving imidapril infusion (5 microg/kg/min), and a diabetic group involving simultaneous imidapril and L-NMMA infusion. Glucose concentrations were maintained around 140 mg/dl during the clamp studies. Plasma insulin levels during the 3 and 30 mU/kg BW/min insulin infusions were 30 and 400 microU/ml, respectively. Glucose infusion rates (GIR) in STZ-induced diabetic rats showed a significant decrease compared to controls. At both insulin infusion rates, imidapril-infused diabetic rats showed an increased GIR, compared with the saline infused ones. There was no significant difference in GIR between L-NMMA and saline infusion in diabetic rats. Simultaneous infusion of imidapril and L-NMMA did not significantly decrease GIR with low-dose insulin infusion, but the increase in GIR induced by imidapril with high-dose insulin infusion was impaired by 100 % by L-NMMA infusion in diabetic rats. These results suggest that imidapril may improve insulin action, in part, via nitric oxide.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Imidazoles/pharmacology , Imidazolidines , Insulin/pharmacology , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Animals , Blood Glucose/analysis , Body Weight , Diabetes Mellitus, Experimental/drug therapy , Glucose/administration & dosage , Glucose Clamp Technique , Imidazoles/administration & dosage , Insulin/administration & dosage , Insulin/blood , Insulin Resistance , Male , Nitric Oxide Synthase/antagonists & inhibitors , Rats , Rats, Wistar , omega-N-Methylarginine/administration & dosageABSTRACT
Currently PMMA is the polymer most commonly used as a bone cement for the fixation of total hip prostheses. Ideally, a bone cement material should be easy to handle, biologically compatible, nonsupporting of oral microbial growth, available in the particulate and molded forms, easy to obtain, nonallergenic, adaptable to a broad range of dental and medical applications, in possession of high compressive strength, and effective in guided tissue regenerative procedures. One of the problems associated with the conventional types of bone cement used is their unsatisfactory mechanical and exothermic reaction properties. The purpose of this in vitro study was to investigate and compare the mechanical properties (three-point bending strength, energy-to-break, and modulus of elasticity) and physical properties (setting time, water sorption, and exothermic heat) of HA/PMMA (HA group) and bovine-bone originated HA/PMMA (BB group) composites. Composites samples were fabricated by admixing method. It was found that the addition of HA and BB particles increased the water sorption. Generally 10 v/o 20 v/o HA and 0 v/o to 10 v/o BB ratio combinations had significant beneficial effects on the mechanical properties. The heat generated during polymerization was influenced by the different admixtures. More than 40 v/o HA and 40 v/o BB should be mixed into PMMA to reduce the peak temperature. Overall evaluation indicated that the BB group had better properties than the HA group.
Subject(s)
Bone Cements/chemistry , Durapatite/chemistry , Materials Testing , Polymethyl Methacrylate/chemistry , Elasticity , Hardness , Macromolecular Substances , Temperature , Tensile Strength , Water/chemistryABSTRACT
The use of a provisional restoration is an important phase in the treatment of the dental prosthetic patient. A good provisional restoration should satisfy the following requirements: pulpal protection, positional stability, ease in cleaning, accurate margins, wear resistance, dimensional stability, and serve as a diagnostic aid in treatment assessment and esthetics. There is a tendency for discoloration, occlusal wear, and fracture that eventually leads to unnecessary repair. Heat-processed and reinforced methacrylate-based resins have been used to improve the mechanical and physical properties of provisional restorations. Among various improvements, the interpenetrating network crosslinked PMMA (IPN) has been shown to have superior mechanical properties if manufactured through a dough compression molding process at 130 degrees C. However, there have been no published data that relate with the use of this material for fixed provisional restorations. The objective of this study was to compare four methyl methacrylate-based resins for provisional crowns and bridges with varying processing cycles, including JET [self-cure], ACRALON [heat-cured], titanium dioxide filled PMMA [heat-cured], and IPN [heat-cured denture tooth resin]. Properties studied included transverse strength, toughness, rigidity, and hardness. From the results of this study the following conclusions can be made: the IPN group may have had a lower degree of conversion as demonstrated by decreased strength, toughness, and hardness data as compared with Acralon. Increasing the polymerization cycle of unmodified Acralon resin causes a significant increase in strength.