Aim To investigate the effects of milrinone (a selective phosphodiesteraseIII inhibitor PDE_3 ) on insulin secretion, blood glucose, plasma free fatty acids (FFA) anddose-response relationship, and assess possible eff...Aim To investigate the effects of milrinone (a selective phosphodiesteraseIII inhibitor PDE_3 ) on insulin secretion, blood glucose, plasma free fatty acids (FFA) anddose-response relationship, and assess possible effects of milrinone on glucose metabolism andinsulin sensitivity in conscious rats. Methods The catheterized nonstressed rats were administeredvarious doses of milrinone (1, 5, 25μmoL·kg^(-1)) and were compared with controls. Ahyperinsulinaemic-eugly-caemic clamp was established in counscious rats, andmilrinone(25μmoL·kg^(-1)) and 25% dimethyl sulfoxide (DMSO, as a control) were given at 120 minduring hyperinsulinaemic-euglycaemic clamping. Glucose turnover was determind with by gaschromatograph mass spectrometer (GC-MS). Results After dosing, plasma FFA levels in 3 milrinonegroups significantly increased, compared with the controls and before dosing. The percentages ofelevation of FFA by the different milrinone doses were very similar, 50%, and 52% , 55% for 1, 5,and 25 μmoL·kg^(-1), repectively, at 2 min after dosing. Plasma insulin levels were significantlyelevated in the 5 and 25 μmoL·kg^(-1) groups, and the effect of milrione on glucose concentrationwas detectable only in 25μmoL·kg^(-1) group. During hyperinsulinaemic clamping, there weresignificant increase, in plasma FFA (from 173 +- 15 to 634 +- 87μmoL·kg^(-1)) and hepatic glucoseproduction (HGP), and a significant decrease in glucose infusion rates (GIR) to about 21% and aslight increase in plasma insulin after milrinone treatment. Conclusion Milrinone impaires theability of insulin to suppress lipolysis and HGP, and insulin-mediated glucose utilization inperipheral tissue. Therefore, milrinone administration may induce an acute insulin resistance invivo.展开更多
Objective： The prevalence of non-alcoholic fatty liver disease （NAFLD） has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship...Objective： The prevalence of non-alcoholic fatty liver disease （NAFLD） has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone （PGZ） acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding. Methods： The rats were separated randomly into 6 groups： model group Ⅰ were fed high fat diet for 8 weeks, PGZ prevention group were given PGZ 4 mg/（kg.d） simultaneously, while control group Ⅰ were fed normal food for 8 weeks; model group Ⅱ were fed high fat diet for 16 weeks, PGZ treatment group were given PGZ 4 mg/（kg.d） orally simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group Ⅱ were fed normal food for 16 weeks. The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase （ALP）, tumor necrosis factor alpha （TNF-α）, fasting blood glucose （FBG）, fasting plasma insulin （FINS）, HOMA （homeostasis model assessment） insulin resistance index （HOMA-IR）, and the liver histology of rats of all groups were assayed. Results： After 8 weeks, the liver in model group Ⅰ showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT, AST, ALP, TNF-α were significantly increased （P〈0.05） compared with control group Ⅰ. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased （P〈0.05） compared with model group Ⅰ. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group Ⅱ rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels ofALT, AST, ALP, FINS and HOMA-IR were significantly increased （P〈0.05） in model group Ⅱ compared with control group Ⅱ. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT, ALP, TNF-α and HOMA-IR were significantly decreased compared with model group Ⅱ. Conclusion： Insulin resistance plays a role in the pathogenesis of NAFLD in rats. Pioglitazone can attenuate insulin resistance and biochemical and histological injury in high fat-induced fatty liver in rats.展开更多
AIM： To investigate the prevalence of the clinical pa- rameters of insulin resistance and diabetes in patients affected by chronic hepatitis C （CHC） or chronic hepa- titis B （CHB）. METHODS： We retrospectively ev...AIM： To investigate the prevalence of the clinical pa- rameters of insulin resistance and diabetes in patients affected by chronic hepatitis C （CHC） or chronic hepa- titis B （CHB）. METHODS： We retrospectively evaluated 852 consec- utive patients （726 CHC and 126 CriB） who had under- gone liver biopsy. We recorded age, sex, ALT, type 2 diabetes and/or metabolic syndrome （MS）, body mass index （BMI）, and apparent disease duration （ADD）. RESULTS： Age, ADD, BMI, prevalence of MS and diabetes in patients with mild/moderate liver fibrosis were significantly higher in CHC. However, the degree of steatosis and liver fibrosis evaluated in liver biop- sies did not differ between CHC and CHB patients. At multivariate analysis, age, sex, BMI, ALT and diabetes were independent risk factors for liver fibrosis in CHC, whereas only age was related to liver fibrosis in CHB. We also evaluated the association between significant steatosis （〉 30%） and age, sex, BMI, diabetes, MS and liver fibrosis. Diabetes, BMI and liver fibrosis were associated with steatosis 〉 30% in CHC, whereas only age and BMI were related to steatosis in CriB. CONCLUSION： These data may indicate that hepatitis C virus infection is a risk factor for insulin resistance.展开更多
Many studies on oxidative stress,insulin resistance,and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free ...Many studies on oxidative stress,insulin resistance,and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free fatty acids metabolism in diabetic and insulin-resistant states.Many pathogenic mechanisms such as insulin receptor substrate phosphorylation are involved in insulin resistance induced by oxidative stress.And antioxidant treatments can show benefits in animal models of diabetes mellitus and insulin resistance.However,negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating diabetic complications.Furthermore,it appears that oxidative stress is only one of the factors contributing to diabetic complications.Thus,antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.展开更多
Objective: To explore the relationship between the β 3-adrenergic receptor(β 3-AR)gene and obesity, T2DM, insulin resistance in Chinese Han population. Methods: Fifty-three healthy subjects, 105 subjects with simp...Objective: To explore the relationship between the β 3-adrenergic receptor(β 3-AR)gene and obesity, T2DM, insulin resistance in Chinese Han population. Methods: Fifty-three healthy subjects, 105 subjects with simple obesity, 63 type 2 diabetic patients without obesity, and 114 type 2 diabetic patients with obesity were studied with the technique of PCR-RFLP in codon 64 of the exon region of β 3-AR gene representing the variation Trp/Arg. Results: Compared with the subjects of Trp homozygous group, the individuals with Arg allele were more elevated in WHR,MBP,SBP,DBP,FBS,PBS,FINS,PINS,FCP,PCP and lower in ISI. Frequency of Arg allele was higher in HINS subgroup without T2DM. Conclusion: The results indicate that the Trp/Arg variation might lead to insulin resistance, obesity and T2DM.β 3-AR gene is supposed to be the candidate gene of insulin resistance, obesity and T2DM in Chinese Han population.展开更多
The IGB （intragastric balloon） is a silicone device, inflated by endoscopy in the gastric cavity, with physiological saline and a blue dye, up to the volume of 700 mL, and used for a maximum of 6 months, It is indic...The IGB （intragastric balloon） is a silicone device, inflated by endoscopy in the gastric cavity, with physiological saline and a blue dye, up to the volume of 700 mL, and used for a maximum of 6 months, It is indicated for patients with BMI〉27 kg/m^2 that have not undergone previous gastric surgery. In obese women there is a decrease in peripheral resistance fertility, and the weight loss achieved in bariatric surgery improves fertility due to reduced subcutaneous fat, with lower insulin resistance. Similar results could be achieved through the use of IGB, a less invasive method. The objective of the article is to report the case of a patient who became pregnant using IGB, considering the hypothesis that the increase in fertility was due to weight loss and/or due to the improvement in the self-esteem （and sexual life） of patient. We selected 13 articles from PubMed, UpToDate, JAMA and a case report. Results： Balloon with drawal occurred on 05/02/16 after positive pregnancy test with final weight 65.5 kg and BMI 25.91 kg/m2. Conclusions： Weight loss actually favors fertility, but self-esteem may have been instrumental in improving the sex life, enabling conception.展开更多
文摘Aim To investigate the effects of milrinone (a selective phosphodiesteraseIII inhibitor PDE_3 ) on insulin secretion, blood glucose, plasma free fatty acids (FFA) anddose-response relationship, and assess possible effects of milrinone on glucose metabolism andinsulin sensitivity in conscious rats. Methods The catheterized nonstressed rats were administeredvarious doses of milrinone (1, 5, 25μmoL·kg^(-1)) and were compared with controls. Ahyperinsulinaemic-eugly-caemic clamp was established in counscious rats, andmilrinone(25μmoL·kg^(-1)) and 25% dimethyl sulfoxide (DMSO, as a control) were given at 120 minduring hyperinsulinaemic-euglycaemic clamping. Glucose turnover was determind with by gaschromatograph mass spectrometer (GC-MS). Results After dosing, plasma FFA levels in 3 milrinonegroups significantly increased, compared with the controls and before dosing. The percentages ofelevation of FFA by the different milrinone doses were very similar, 50%, and 52% , 55% for 1, 5,and 25 μmoL·kg^(-1), repectively, at 2 min after dosing. Plasma insulin levels were significantlyelevated in the 5 and 25 μmoL·kg^(-1) groups, and the effect of milrione on glucose concentrationwas detectable only in 25μmoL·kg^(-1) group. During hyperinsulinaemic clamping, there weresignificant increase, in plasma FFA (from 173 +- 15 to 634 +- 87μmoL·kg^(-1)) and hepatic glucoseproduction (HGP), and a significant decrease in glucose infusion rates (GIR) to about 21% and aslight increase in plasma insulin after milrinone treatment. Conclusion Milrinone impaires theability of insulin to suppress lipolysis and HGP, and insulin-mediated glucose utilization inperipheral tissue. Therefore, milrinone administration may induce an acute insulin resistance invivo.
文摘Objective： The prevalence of non-alcoholic fatty liver disease （NAFLD） has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone （PGZ） acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding. Methods： The rats were separated randomly into 6 groups： model group Ⅰ were fed high fat diet for 8 weeks, PGZ prevention group were given PGZ 4 mg/（kg.d） simultaneously, while control group Ⅰ were fed normal food for 8 weeks; model group Ⅱ were fed high fat diet for 16 weeks, PGZ treatment group were given PGZ 4 mg/（kg.d） orally simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group Ⅱ were fed normal food for 16 weeks. The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase （ALP）, tumor necrosis factor alpha （TNF-α）, fasting blood glucose （FBG）, fasting plasma insulin （FINS）, HOMA （homeostasis model assessment） insulin resistance index （HOMA-IR）, and the liver histology of rats of all groups were assayed. Results： After 8 weeks, the liver in model group Ⅰ showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT, AST, ALP, TNF-α were significantly increased （P〈0.05） compared with control group Ⅰ. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased （P〈0.05） compared with model group Ⅰ. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group Ⅱ rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels ofALT, AST, ALP, FINS and HOMA-IR were significantly increased （P〈0.05） in model group Ⅱ compared with control group Ⅱ. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT, ALP, TNF-α and HOMA-IR were significantly decreased compared with model group Ⅱ. Conclusion： Insulin resistance plays a role in the pathogenesis of NAFLD in rats. Pioglitazone can attenuate insulin resistance and biochemical and histological injury in high fat-induced fatty liver in rats.
文摘AIM： To investigate the prevalence of the clinical pa- rameters of insulin resistance and diabetes in patients affected by chronic hepatitis C （CHC） or chronic hepa- titis B （CHB）. METHODS： We retrospectively evaluated 852 consec- utive patients （726 CHC and 126 CriB） who had under- gone liver biopsy. We recorded age, sex, ALT, type 2 diabetes and/or metabolic syndrome （MS）, body mass index （BMI）, and apparent disease duration （ADD）. RESULTS： Age, ADD, BMI, prevalence of MS and diabetes in patients with mild/moderate liver fibrosis were significantly higher in CHC. However, the degree of steatosis and liver fibrosis evaluated in liver biop- sies did not differ between CHC and CHB patients. At multivariate analysis, age, sex, BMI, ALT and diabetes were independent risk factors for liver fibrosis in CHC, whereas only age was related to liver fibrosis in CHB. We also evaluated the association between significant steatosis （〉 30%） and age, sex, BMI, diabetes, MS and liver fibrosis. Diabetes, BMI and liver fibrosis were associated with steatosis 〉 30% in CHC, whereas only age and BMI were related to steatosis in CriB. CONCLUSION： These data may indicate that hepatitis C virus infection is a risk factor for insulin resistance.
基金Supported by grant from the National Basic Research Program (973Program) (2006CB503903)
文摘Many studies on oxidative stress,insulin resistance,and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free fatty acids metabolism in diabetic and insulin-resistant states.Many pathogenic mechanisms such as insulin receptor substrate phosphorylation are involved in insulin resistance induced by oxidative stress.And antioxidant treatments can show benefits in animal models of diabetes mellitus and insulin resistance.However,negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating diabetic complications.Furthermore,it appears that oxidative stress is only one of the factors contributing to diabetic complications.Thus,antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.
文摘Objective: To explore the relationship between the β 3-adrenergic receptor(β 3-AR)gene and obesity, T2DM, insulin resistance in Chinese Han population. Methods: Fifty-three healthy subjects, 105 subjects with simple obesity, 63 type 2 diabetic patients without obesity, and 114 type 2 diabetic patients with obesity were studied with the technique of PCR-RFLP in codon 64 of the exon region of β 3-AR gene representing the variation Trp/Arg. Results: Compared with the subjects of Trp homozygous group, the individuals with Arg allele were more elevated in WHR,MBP,SBP,DBP,FBS,PBS,FINS,PINS,FCP,PCP and lower in ISI. Frequency of Arg allele was higher in HINS subgroup without T2DM. Conclusion: The results indicate that the Trp/Arg variation might lead to insulin resistance, obesity and T2DM.β 3-AR gene is supposed to be the candidate gene of insulin resistance, obesity and T2DM in Chinese Han population.
文摘The IGB （intragastric balloon） is a silicone device, inflated by endoscopy in the gastric cavity, with physiological saline and a blue dye, up to the volume of 700 mL, and used for a maximum of 6 months, It is indicated for patients with BMI〉27 kg/m^2 that have not undergone previous gastric surgery. In obese women there is a decrease in peripheral resistance fertility, and the weight loss achieved in bariatric surgery improves fertility due to reduced subcutaneous fat, with lower insulin resistance. Similar results could be achieved through the use of IGB, a less invasive method. The objective of the article is to report the case of a patient who became pregnant using IGB, considering the hypothesis that the increase in fertility was due to weight loss and/or due to the improvement in the self-esteem （and sexual life） of patient. We selected 13 articles from PubMed, UpToDate, JAMA and a case report. Results： Balloon with drawal occurred on 05/02/16 after positive pregnancy test with final weight 65.5 kg and BMI 25.91 kg/m2. Conclusions： Weight loss actually favors fertility, but self-esteem may have been instrumental in improving the sex life, enabling conception.
