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Objective To establish the hyperinsulinemic-euglycemic clamp(HEC) technique in conscious rats, and to explore the effect of acute infusion of lipid on glucose infusion rate (GIR) in rats. Methods Ten SD rats were random-ly divided into two groups, 5 rats for each group. The right jugular vein and left carotid artery were catheterized and under-went a HEC with infusion of lipid (intralipid group) for 6 hours, and with continuing infusion of 5%glucose (control group). The plasma levels of free fatty acid(FFA) and GIR were measured by HEC method. Results The level of FFA concentration increased by 17.6-fold, and GIR was reduced by 27%in the intralipid group compared to those of control group (P＜0.001). Conclusion The rat model of HEC has been successfully established by intravenous intralipid infusion, which can be con-firmed by HEC technique.
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As the 21st century advances, evidence-based medicine (EBM) has come to be regarded as essential in all field of medical sciences and practical medicine. Creating medicines have been searching for based on EBM and development of new medicine has been carried out.In Japan the number of diabetic patients has increased to 129% during recent 10 years. The number of diabetic complications has also increased and hemodyalysis has been introduced in approximately 16,000 patients/year with diabetic nephropathy in Japan in 2008.Additinally many diabetic patients are suffering from numbness, cold sensation and pains in extremities derived from diabetic neuropathy. Therefore reduction of diabetic complications is one of the most important considerations in the field of diabetic patient care.Diabetes mellitus is equivalent to wasting-thirst in Jomgiiyaolue.We have reported the effectiveness of Goshajinkigan (GJG) for the treatment of nembness associated with diabetic neuropathy for the first time in Japan in 1984.In controlled comparative study, GJG showed significantly higher rates of improvement of this symptom versus mechobalamin.Insulin resistance has an important role on the occurrence of type 2 diabetes and metabolic syndrome.We have studies the effects of Kampo medicine on the insulin resistance using the euglycemic clamp and molecular biological techniques.1) Animal experimental studies: The improvement of insulin resistance in STZ rats by the administration of GJG might be via NO pathway and due, at least in part, to correct in the abnormal early steps of insulin signaling pathway in skeletal muscle.2) Clinical Studies: Effects of GJG on insulin resistance in patients with type 2 diabetes were investigated. HOMA-R was significantly decreased after GJG treatment (P=0.019). On the other hand, HOMA-R in the control group did not show significant difference. HOMA-R returned to the pre GJG treatment level1month after GJG discontinuation (P=0.018). The high-dose clamp resulted in a significantly increased insulin action (MCR levels) after GJG treatment.These animal experimental and clinical studies suggest that GJG might be effective for improving insulin resistance in the patients with type 2 diabetes.Kampo formulations might be useful not only for the prevention and the treatment of diabetic complications but also effective for the prevention and treatment of type 2 diabetes.In conclusion GJG has been used for the treatment of numbness and dysnuria since the statement in Yanshijishengfang. We have found the effectiveness of GJG on the treatment of diabetic neuropathy and on the prevention and the treatment of type 2 diabetes. We would like to continue these scientific activities.
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Objective To evaluate the application value of hyperinsulinemic euglycemic clamp in the diagnosis and treatment of newly-onset diabetic patients. Methods Totally 11 newly-onset diabetic inpatients (10 patients with type 2 diabetes mellitus and 1 patient with latent autoimmune diabetes of adulthood) who were diagnosed in the Department of Endocrinology of Peking Union Medical College Hospital from January 2009 to August 2009 were included in this study. Hyperinsulinemic euglycemic clamp was applied to measure the glucose disposal rate (M value). Afterwards insulin pump therapy was applied and the total insulin dosage per day to get to the target of the fasting and postprandial blood glucose was calculated. Final]y the relationships between insulin dosage per day and the M value, body mass index (BMI) , fasting blood glucose, fasting insulin level were separately analyzed. Results The insulin dosage was only negatively correlated with M value (r = - 0. 83, P = 0. 003), and was not significantly correlated with BMI (r = 0.54, P = 0.106), fasting blood glucose (r = - 0. 16, P =0. 657) , and fasting insulin (r = 0. 16, P = 0. 659). The formula of insulin dosage and M value according to the mathematic model as follows: insulin dosage per day = - 3. 327 M + 49. 849. Conclusion Hyperinsulinemic euglycemic clamp can effectively evaluate the insulin sensitivity in the newly-onset type 2 diabetic patients, and thus can be a useful tool in deciding the clinical insulin dosage.
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Objective To establish a euglycemic clamp technique in beagle dogs. Methods The euglycemic clamp technique was applied in healthy beagle dogs and the blood glucose, insulin, C-peptide, insulin and glucagon were monitored during the clamp. Results The blood glucose was controlled within the basal level.The coefficient of variation was less than 5% during the clamp. The serum insulin concentration finally reached(40.0±3.8)mIU/L stably and a significant inhibition was shown in endogenous insulin by the determination of C-peptide. But there was no significant increase in serum glucagon compared with basal values.Conclusion Methodology confirmed that the euglycemic clamp technique is successful in beagle dogs and can be applied in the study of pharmacodynamics of insulin preparations.
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emic euglycemic clamp quantitively.
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<b>Background</b><br>Although there are several reports that electroacupuncture (EA) in the abdomen reduces fasting blood glucose and improves insulin sensitivity, the effects under a glucose load or hyperinsulinemic conditions have not yet been studied. In this study, we investigated the effect of EA at Zhongwan (CV12) under the conditions of an intravenous glucose tolerance test (IVGTT) and a hyperinsulinemic euglycemic clamp in normal Sprague-Dawlay (SD) rats.<br><b>Methods</b><br>Male SD rats were anesthetized with pentobarbital (40mg/kg i. p.) and then maintained by continuous infusion through a tail vein. Blood samples were drawn from the ventral tail artery during the fasting stage (baseline and 30min after), and at 2, 5, 10, 20, 30, 45, 60min after a glucose load (0.5g/kg). EA was performed for 30min (EA30, n=8) during the fasting stage and for 90min (EA90, n=8) during both the fasting and IVGTT periods. In the hyperinsulinemic euglycemic clamp experiments, insulin (2mU/kg/min) was infused through the tail vein, followed by infusion of 20% glucose at variable rates to maintain fasting blood glucose levels. EA was performed for 40min after a steady-state was achieved.<br><b>Results</b><br>Significant decreases in fasting blood glucose and increase in plasma insulin concentration were observed during the fasting period in rats in both the EA30 and EA90 groups, whereas rats in the control group (n=8) which did not receive any EA stimulation showed no such changes. Total glucose levels during the IVGTT were lower in the EA30 and EA90 groups compared to controls, with a significantly higher level of relative insulin secretion. During the hyperinsulinemic euglycemic clamp, glucose consumption was increased significantly by EA stimulation with a marked increase in both insulin concentration and sensitivity.<br><b>Conclusion</b><br>EA at CV12 accelerates glucose consumption during IVGTT and hyperinsulinemic conditions probably as a consequence of increased insulin sensitivity and/or increased plasma insulin concentration.
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Recently in Japan, the numbers of diabetic patients have been increased to 7.4 million and to 16.2 millions if the subjects of impaired glucose tolerance are added. Most Japanese diabetic patients are type 2 (non-insulin dependent). Decreased secretion of insulin and insulin resistance play important roles on the occurrence and progression of type 2 diabetes.<br>Long-established systems of traditional medicine have evolved from systematic recordings of human evidence for more than 3 thousands years. In addition the traditional Chinese medicinal philosophy is one of the oldest medical sciences in the world and has a long-standing history in the usage of herbal medicinals. Nowadays the use of complementary/alternative medicine and especially the consumption of botanicals has been increasing rapidly worldwide.<br>1. Clinical Studies<br>The management of diabetic neuropathy is one of the most difficult clinical problems. Among 65 patients with diabetic neuropathy who suffered from numbness of lower extremities 43 (66.2%) experienced some degree of improvement after oral administration of Goshajinkigan (GJG). Following our first report, more than 10 papers were published in Japan and almost same results were obtained. In a well-controlled comparative study, the efficacy of GJG and mecobalamin in diabetic neuropathy was estimated. After oral administration of GJG, the general improvement rate was 80.0%, while it was 48.1% in mecobalamin. The difference between the two groups was statistically significant (P<0.01). These results suggested that GJG is a useful medicine for amelioration of numbness due to diabetic neuropathy.<br>2. Animal experimental studies<br>Regular physical training has been known to be beneficial in the prevention and the treatment of life-style related diseases such as type 2 diabetes. However, it is very difficult for diabetic patients to continue physical exercise training for a long time. Troglitazone has insulin-sensitizing actions but it withdrew because of severe fatal hepato-toxic actions. Therefore development of insulin-sensitizing medicine without significant side-effects have been expected.<br>Chinese herbal medicine has less frequent side effects when compared to modern western medicine.<br>In the present study, the effect of GJG on insulin resistance in streptozotocin (STZ, 50mg kg<sup>-1</sup> BW, ivy.)-induced diabetic rats was examined by means of the euglycemic clamp procedure.<br>The improvement of impaired insulin action in STZ-diabetic rats by single and repeated administration of GJG may be due, at least in part, to enhance insulin signaling, and subsequent ameliorated production of NO. In conclusion, <br>(1) Diagnosis and primary treatment to reduce blood glucose including diet, exercise, oral hypoglycemic agents and insulin should be practiced by western style medical sciences. (2) Kampo medication is useful for the prevention and treatment of diabetic complications. (3) Kampo medicine has the possibility of prevention of type 2 diabetes.
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Objective:To establish a hyperinsulinemic euglycemic clamp technique for the study of insulin sensitivity in Chinese.Methods:A hyperinsulinemic euglycemic clamp technique was used to the study of methodology in 8 normal weight subjects with normal glucose tolerance.Results:(1)When a higher level of insulin was created during maintaining fasting euglycemia,the secretion of endogenous insulin and hepatic glucose production were completely inhibited.The secretion of counter-regulatory hormones(cortisol,growth hormone and glucagon) was not significantly stimulated..(2)During the steady-state of hyperinsulinemic euglycemic clamp,the glucose disposal rate was 9.25?0.25mg/(kg.min)Conclusion:The hyperinsulinemic euglycemic clamp technique was established successfully in Chinese.During the steady-state of exogenous insulin and glucose metabolism,glucose utilization increased.
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Objective To compare the differences between C-peptide and insulin in evaluation of insulin resistance.Methods From 2003 to 2004,according to oral 75 g glucose tolerance test(OGTT),44 subjects were divided into normal glucose tolerance(NGT)group,isolated impaired fasting glucose(I-IFG)group,isolated impaired glucose tolerance(I-IGT)group and combined impaired glucose tolerance(C-IGT)group.We discussed the relationship between glucose infusion rate(GIR)by hyperinsulin euglycemic clamp and IAI,HOMA-IR,QUICKI(these indexes from fasting insulin level),fasting C-peptide level,respectively.Results (1)GIR of I-IFG,I-IGT,C-IGT groups declined significantly compared with that of NGT group(P0.05).IAI,HOMA-IR and QUICKI of each group were of good relation to GIR respectively(P0.05),whose relative rates were among 0.394~0.042.Conclusion The level of fasting C-peptide has no relationship wiht the degree of insulin resistance.
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Objective To establish an extended hyperinsulinemic euglycemic clamp for the study of insulin sensitivity in Chinese. Methods Combining glucose clamp, 3 3H labelled glucose tracer technique and indirect calorimetry, an extended hyperinsulinemic euglycemic clamp technique was applied into the study of methodology in 9 normal weight subjects with normal glucose tolerance. Results (1) When a higher level of insulin was created during maintaining euglycemia, hepatic glucose production was completely inhibited, and the counter regulatory hormones (including cortisol, growth hormone and glucagon) and endogenous insulin secretion were not significantly stimulated. (2) During the steady state of the extended hyperinsulinemic euglycemic clamp, the insulin mediated glucose disappearance rate was significantly increased compared with basal state 〔(5.86?0.65)mg?kg -1 ?min -1 vs (2.45?0.15)mg?kg -1 ?min -1 , P
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The effect of adrenomedullin (AM) on insulin sensitivity in normal Wistar rats was investigated by hyperinsulinemic-euglycemic clamp in combination with isotope dilution technique. The infusion rates of AM during the clamp were 0, 0.05, 0.2, 1 ?g?kg~(-1)?min~(-1), rspectively. The glucose disposal rate (GDR) and hepatic glucose output (HGO) were calculated by the plasma 3-~(3)H-glucose specific activity. After AM infusion, the insulin-mediated glucose disposal was reduced in a dose-dependant manner. It indicated that high dose of AM could induce a marked state of insulin resistance, which was mainly characterized by inhibition of the effect of insulin to stimulate peripheral glucose metabolism.
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To investigate the effect of electro-acupuncture stimulation (EAS) on insulin sensitivity in rats, we performed several stimulations on Otsuka Long Evans Tokushima Fatty (OLETF) rats, during euglycemic clamp. We divided OLETF rats into five groups according to the kind of the stimulation: EAS at vagal innervated region of the auricle (AVA), EAS at non-vagal innervated region of the auricle (ANVA), EAS on the back of the body (AB), pinching on the back of the body (PB), and no stimulation on the body (NS). These procedures were also applied on Long Evans Tokushima Otsuka (LETO) rats as a control study.<br>Furthermore, we performed long-term stimulation (from six to 24 weeks of age) on OLETF rats to assess the preventive effect of those stimulations on the formation of the insulin resistance. EAS of pulse duration 300ms, 1.5V, 1Hz was applied for 10 or 15minutes. As a result, the glucose infusion rate (GIR) showed significantly higher levels during stimulation of PB group in LETO rats. On the other hand, the GIR of AVA group in LETO rats and PB group in OLETF rats were decreased by stimulation. The GIR in AVA group and AB group after long-term stimulation were significantly higher than those of NS group in OLETF rats. These results suggested that EAS at the auricle and the back is useful for the prevention of the formation of insulin resistance when it's applied before onset of the symptoms in OLETF rats.
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Physical training has been shown to improve glucose tolerance and insulin action in peripheral tissues. In the present study, regular (R) and high (H) -dose euglycemic clamp procedures were performed to determine the effects of different types of physical training on insulin action (sensitivity/responsiveness) in 10 long-distance runners (LR), 10 weight-lifters (WL) and 12 healthy controls (HC), The amount of infused glucose (glucose metabolism, GM) during euglycemic clamping is a measure of the peripheral tissue sensitivity and/or responsiveness to insulin. For R clamping, when GM was calculated per unit body weight (BW), GM in LR (11.92±1.22 mg/kg BW·min) and WL (9.28±0.63 mg/kg BW·min) was significantly (P<0.05) higher than that in HC (7.44±0.39 mg/kg BW·min) . When calculated per unit lean body mass (LBM), LR (15.07±1.56 mg/kg LBM·min) differed from HC (9, 15±0.59 mg/kg LBM·min, P<0.05), whereas the value in WL (11.50±0.93mg/kg LBM·min) was identical to that in HC. For H clamping, there was no significant change in these three groups when GM was calculated per unit BW or LBM. These results suggest that enhancement of insulin action by physical training is due to an increase in insulin sensitivity, rather than to an increase in insulin responsiveness, and that aerobic exercise, for example long-distance running, is more effective for the improvement of decreased sensitivity to insulin, which is observed in patients with simple obesity and diabetes, than anaerobic exercise such as weight-lifting.
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Objective:To establish a hyperinsulinemic euglycemic clamp technique in conscious rat,and to explore the effect of anesthesia and acute infusion of lipid on insulin sensitivity of rats.Methods:Rats divided into two groups were catheterized in the right jugular vein and left carotid artery and underwent a hyperinsulinemic-euglycemic clamp with or without infusion of lipid (Intralipid) and in unconscious and conscious state.Results:Infusion of lipid resulted in a decrease of insulin sensitivity by 30%( P
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0.05.Conclusion:The prior glucose bolus does not affect the following euglycemic clamp.The Botnia clamp is a useful method for simultaneous independent assessment of insulin secretion and insulin sensitivity.
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Objective: To study the effect of the ryegrass powder on the insulin resistance in obese rats. Method: Thirty four Wistar rats were divided into three groups by random:control group fed with normal diet, both obese group and ryegrass powder group fed with high lipid diet for 6 w and then the ryegrass powder group fed ryegrass powder of 0 and 2 g/(kg bw?d) respectively for 4 w. Then blood lipids, glucose,free fatty acid and insulin were measured. Euglycemic clamp technique was used. Results: The blood glucose, insulin, TG, TCH, LDL and FFA of the obese group were obviously (P