AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar...AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P < 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.展开更多
Objective Hypoglycemic Ziyabiti Tablets(HZT)is a traditional multicomponent treatment for diabetes in Xinjiang Uyghur Traditional Medicine.The present study aimed to investigate the effect of HZT in diabetic rats and ...Objective Hypoglycemic Ziyabiti Tablets(HZT)is a traditional multicomponent treatment for diabetes in Xinjiang Uyghur Traditional Medicine.The present study aimed to investigate the effect of HZT in diabetic rats and its activity in cultured liver cells to investigate the relative mechanisms.Methods 10 days high-fat diet fed rats were intraperitoneally injected with alloxan(ALX)at next two subsequent days to induce diabetes mellitus(DM).Then were divided into 5 groups:saline,positive DM control and DM groups treated with different doses of HZT.Fasting blood glucose(FBG),total cholesterol(TC),total triglycerides(TG),high-density lipoprotein(HDL-C),fasting insulin(FI),insulin secretion(IS)and insulin sensitivity index(ISI)were measured.The IC_(50) of HZT in L-02 cells was determined by MTT assay,in intact and in paracetamol-induced liver injury(Par),on lactate dehydrogenase(LDH)activity and on glucose consumption.Results HZT decreased FBG and TC(P <0.05),increased IS(P <0.05)and at 440 mg·kg^(-1)·d^(-1) increased FI(P < 0.01).In vitro,HZT at 0.1,0.2,and 0.4 mg/mL decreased LDH activity and promoted glucose consumption.Conclusion The hypoglycemic mechanism of HZT is possibly related to increased insulin secretion from the pancreas and increased utilization of glucose by the liver.展开更多
OBJECTIVE: To study the activity of liver glycogen synthase in analogous model of NIDDM rats. METHODS: Male Wistar rats were injected with low dose of streptozotocin (STZ) (30 mg/kg body weight) via tail vena and thos...OBJECTIVE: To study the activity of liver glycogen synthase in analogous model of NIDDM rats. METHODS: Male Wistar rats were injected with low dose of streptozotocin (STZ) (30 mg/kg body weight) via tail vena and those animals with glucose tolerance impaired and level of insulin equal to or higher than that of the controls at 18th week were taken as the analogous rat model of NIDDM. The activity of liver glycogen synthase (GS) was assayed at the end of experiment. RESULTS: Type I-enzyme: 0.18 +/- 0.06 mumol/min.g versus 0.24 +/- 0.09 mumol/min.g, P展开更多
AIM:In previous experiments we have demonstrated that by administering low doses of cholecystokinin-octapeptide (CCK-8),the process of regeneration following L-arginine (Arg)-induced pancreatitis is accelerated.In rat...AIM:In previous experiments we have demonstrated that by administering low doses of cholecystokinin-octapeptide (CCK-8),the process of regeneration following L-arginine (Arg)-induced pancreatitis is accelerated.In rats that were also diabetic(induced by streptozotocin,STZ),pancreatic regeneration was not observed.The aim of this study was to deduce whether the administration of exogenous insulin could in fact restore the hypertrophic effect of CCK-8 in diabetic-pancreatitic rats. METHODS:Male Wistar rats were used for the experiments. Diabetes mellitus was induced by administering 60mg/kg body mass of STZ intraperitoneally(i.p.),then,on d 8, pancreatitis was induced by 200mg/100 g body mass Arg i.p.twice at an interval of 1 h.The animals were injected subcutaneously twice daily(at 7 a.m.and 7 p.m.)with 1 μg/kg of CCK-8 and/or 2 IU mixed insulin(300g/L short- action and 700g/L intermediate-action insulin) for 14 d after pancreatitis induction.Following this the animals were killed and the serum amylase,glucose and insulin levels as well as the plasma glucagon levels,the pancreatic mass/body mass ratio(pm/bm),the pancreatic contents of DNA,protein,amylase,lipase and trypsinogen were measured.Pancreatic tissue samples were examined by light microscopy on paraffin-embedded sections. RESULTS:In the diabetic-pancreatitic rats treatment with insulin and CCK-8 significantly elevated pw/bm and the pancreatic contents of protein,amylase and lipase vs the rats receiving only CCK-8 treatment.CCK-8 administered in combination with insulin also elevated the number of acinar cells with mitotic activities,whereas CCK-8 alone had no effect on laboratory parameters or the mitotic activities in diabetic-pancreatitic rats. CONCLUSION:Despite the hypertrophic effect of CCK-8 being absent following acute pancreatitis in diabetic-rats, the simultaneous administration of exogenous insulin restored this effect.Our results clearly demonstrate that insulin is necessary for the hypertrophic effect of low-doses of CCK-8 following acute pancreatitis.展开更多
Increased reactive oxygen species by the activation of NADPH oxidase（NOX） contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabe...Increased reactive oxygen species by the activation of NADPH oxidase（NOX） contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabetic rats.We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level.Rat models of streptozotocin-induced diabetes were treated with apocynin（30 and 100 mg/kg per day,intragastrically） for 4 weeks.Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer.Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively.Streptozotocin injection reduced pain threshold in analgesimeter,but not in aesthesiometer.Apocynin treatment increased pain threshold dose-dependently.Western blot analysis showed an increase in catalase and NOX-p47 phox protein expression in the spinal cord.However,protein expressions of neuronal and inducible nitric oxide synthase（n NOS,i NOS）,superoxide dismutase,glutathion peroxidase,nitrotyrosine,tumor necrosis factor-α,interleukin-6,interleukin-1β,aldose reductase,cyclooxygenase-2 or MAC-1（marker for increased microgliosis） in the spinal cord remained unchanged.Western blot analysis results also demonstrated that apocynin decreased NOX-p47 phox expression at both doses and catalase expression at 100 mg/kg per day.Histochemistry of diabetic sciatic nerve revealed marked degeneration.n NOS and i NOS immunoreactivities were increased,while S-100 immunoreactivity（Schwann cell marker） was decreased in sciatic nerve.Apocynin treatment reversed these changes dose-dependently.In conclusion,decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss.Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats.展开更多
The Effects of electroacupuncture (EA) at Weiwanxiashu (EX-B3) and Zusanli (ST 36) points on blood glucose (BG) and plasma pancreatic glucagon (PG) contents were dynamically observed in diabetic rabbits induced by All...The Effects of electroacupuncture (EA) at Weiwanxiashu (EX-B3) and Zusanli (ST 36) points on blood glucose (BG) and plasma pancreatic glucagon (PG) contents were dynamically observed in diabetic rabbits induced by Alloxan. It is found that acupuncture at Weiwanxiashu point can significantly lower the BG content and inhibit release of PG; no significant changes in BG and PG are found when acupuncture is given at Zusanli (ST 36) point alone, however BG and PG contents decrease more obviously when acupuncture employed at both Zusanli and Weiwanxiashu, suggesting that Zusanli has a marked synergetic action with Weiwanxiashu.展开更多
基金Supported by Russian Science Foundation,No.17-75-30052
文摘AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P < 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.
文摘Objective Hypoglycemic Ziyabiti Tablets(HZT)is a traditional multicomponent treatment for diabetes in Xinjiang Uyghur Traditional Medicine.The present study aimed to investigate the effect of HZT in diabetic rats and its activity in cultured liver cells to investigate the relative mechanisms.Methods 10 days high-fat diet fed rats were intraperitoneally injected with alloxan(ALX)at next two subsequent days to induce diabetes mellitus(DM).Then were divided into 5 groups:saline,positive DM control and DM groups treated with different doses of HZT.Fasting blood glucose(FBG),total cholesterol(TC),total triglycerides(TG),high-density lipoprotein(HDL-C),fasting insulin(FI),insulin secretion(IS)and insulin sensitivity index(ISI)were measured.The IC_(50) of HZT in L-02 cells was determined by MTT assay,in intact and in paracetamol-induced liver injury(Par),on lactate dehydrogenase(LDH)activity and on glucose consumption.Results HZT decreased FBG and TC(P <0.05),increased IS(P <0.05)and at 440 mg·kg^(-1)·d^(-1) increased FI(P < 0.01).In vitro,HZT at 0.1,0.2,and 0.4 mg/mL decreased LDH activity and promoted glucose consumption.Conclusion The hypoglycemic mechanism of HZT is possibly related to increased insulin secretion from the pancreas and increased utilization of glucose by the liver.
文摘OBJECTIVE: To study the activity of liver glycogen synthase in analogous model of NIDDM rats. METHODS: Male Wistar rats were injected with low dose of streptozotocin (STZ) (30 mg/kg body weight) via tail vena and those animals with glucose tolerance impaired and level of insulin equal to or higher than that of the controls at 18th week were taken as the analogous rat model of NIDDM. The activity of liver glycogen synthase (GS) was assayed at the end of experiment. RESULTS: Type I-enzyme: 0.18 +/- 0.06 mumol/min.g versus 0.24 +/- 0.09 mumol/min.g, P
基金Supported by The Wellcome Trust Grant No.022618,and by the Hungarian Scientific Research Fund D42188,T43066 and T042589
文摘AIM:In previous experiments we have demonstrated that by administering low doses of cholecystokinin-octapeptide (CCK-8),the process of regeneration following L-arginine (Arg)-induced pancreatitis is accelerated.In rats that were also diabetic(induced by streptozotocin,STZ),pancreatic regeneration was not observed.The aim of this study was to deduce whether the administration of exogenous insulin could in fact restore the hypertrophic effect of CCK-8 in diabetic-pancreatitic rats. METHODS:Male Wistar rats were used for the experiments. Diabetes mellitus was induced by administering 60mg/kg body mass of STZ intraperitoneally(i.p.),then,on d 8, pancreatitis was induced by 200mg/100 g body mass Arg i.p.twice at an interval of 1 h.The animals were injected subcutaneously twice daily(at 7 a.m.and 7 p.m.)with 1 μg/kg of CCK-8 and/or 2 IU mixed insulin(300g/L short- action and 700g/L intermediate-action insulin) for 14 d after pancreatitis induction.Following this the animals were killed and the serum amylase,glucose and insulin levels as well as the plasma glucagon levels,the pancreatic mass/body mass ratio(pm/bm),the pancreatic contents of DNA,protein,amylase,lipase and trypsinogen were measured.Pancreatic tissue samples were examined by light microscopy on paraffin-embedded sections. RESULTS:In the diabetic-pancreatitic rats treatment with insulin and CCK-8 significantly elevated pw/bm and the pancreatic contents of protein,amylase and lipase vs the rats receiving only CCK-8 treatment.CCK-8 administered in combination with insulin also elevated the number of acinar cells with mitotic activities,whereas CCK-8 alone had no effect on laboratory parameters or the mitotic activities in diabetic-pancreatitic rats. CONCLUSION:Despite the hypertrophic effect of CCK-8 being absent following acute pancreatitis in diabetic-rats, the simultaneous administration of exogenous insulin restored this effect.Our results clearly demonstrate that insulin is necessary for the hypertrophic effect of low-doses of CCK-8 following acute pancreatitis.
基金supported by the Research Fund of Ege University(Project No.2010-TIP-076)
文摘Increased reactive oxygen species by the activation of NADPH oxidase（NOX） contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabetic rats.We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level.Rat models of streptozotocin-induced diabetes were treated with apocynin（30 and 100 mg/kg per day,intragastrically） for 4 weeks.Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer.Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively.Streptozotocin injection reduced pain threshold in analgesimeter,but not in aesthesiometer.Apocynin treatment increased pain threshold dose-dependently.Western blot analysis showed an increase in catalase and NOX-p47 phox protein expression in the spinal cord.However,protein expressions of neuronal and inducible nitric oxide synthase（n NOS,i NOS）,superoxide dismutase,glutathion peroxidase,nitrotyrosine,tumor necrosis factor-α,interleukin-6,interleukin-1β,aldose reductase,cyclooxygenase-2 or MAC-1（marker for increased microgliosis） in the spinal cord remained unchanged.Western blot analysis results also demonstrated that apocynin decreased NOX-p47 phox expression at both doses and catalase expression at 100 mg/kg per day.Histochemistry of diabetic sciatic nerve revealed marked degeneration.n NOS and i NOS immunoreactivities were increased,while S-100 immunoreactivity（Schwann cell marker） was decreased in sciatic nerve.Apocynin treatment reversed these changes dose-dependently.In conclusion,decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss.Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats.
文摘The Effects of electroacupuncture (EA) at Weiwanxiashu (EX-B3) and Zusanli (ST 36) points on blood glucose (BG) and plasma pancreatic glucagon (PG) contents were dynamically observed in diabetic rabbits induced by Alloxan. It is found that acupuncture at Weiwanxiashu point can significantly lower the BG content and inhibit release of PG; no significant changes in BG and PG are found when acupuncture is given at Zusanli (ST 36) point alone, however BG and PG contents decrease more obviously when acupuncture employed at both Zusanli and Weiwanxiashu, suggesting that Zusanli has a marked synergetic action with Weiwanxiashu.
