Diabetes mellitus is the most common metabolic disease and its prevalence is increasing in many countries year by year.More than 90% of diabetes patients are type 2 diabetes,which is caused by insulin resistance and b...Diabetes mellitus is the most common metabolic disease and its prevalence is increasing in many countries year by year.More than 90% of diabetes patients are type 2 diabetes,which is caused by insulin resistance and beta-cell dysfunction.In this paper,the oligomannuronate-chromium(III)complex(OM2)was prepared and its effect and mechanism on attenuating insulin resistance in diabetic C57BL/KsJ-db/db mice were studied.The results indicated that oral intake of OM2(50 mg kg-1d-1)for 42 d decreased blood glucose and lipid concentration,which was associated with the reduced serum insulin concentration and insulin resistance.According to western blot assay,OM2 could activate AMPK pathway to regulate glycogen synthesis,gluconeogenesis and lipid metabolism in the liver,and attenuate the hyperglycemic symptom in db/db mice.The effects of OM2 on attenuating insulin resistance were com-parable to that of the established antidiabetic drug metformin,and OM2 showed less adverse effect than metformin in vivo.Based on the effectiveness and low toxicity,OM2 may potentially be used for prevention and treatment of type 2 diabetes mellitus.展开更多
AIM: To test whether oral L-81 treatment could im-prove the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetica...AIM: To test whether oral L-81 treatment could im-prove the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetically diabetic (db/db) mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db/db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mecha-nism, HepG2 cells were treated with L-81 and the effects on apolipoprotein B (apoB) secretion and mRNA level of the MTP gene were assessed.RESULTS: Treatment of db/db mice with L-81 sig-nificantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also signif icantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter. CONCLUSION: L-81 represents a promising candidate in the development of a selective insulin-mimetic mol-ecule and an anti-diabetic agent.展开更多
Background Diabetic macrovascular complications are important causes of cardiovascular and cerebrovascular diseases and also one of the major causes of morbidity and mortality in patients with type 2 diabetes mellitus...Background Diabetic macrovascular complications are important causes of cardiovascular and cerebrovascular diseases and also one of the major causes of morbidity and mortality in patients with type 2 diabetes mellitus （T2DM）. Phlorizin has been reported to be effective in reducing the blood glucose level in diabetic mellitus, while little is known about its effects on vascular complications. This study aimed to observe the effects of phlorizin on the aorta of diabetes db/db mice and explore its mechanism. Methods Diabetic db/db mice （n=16） and age-matched db/m mice （n=8） were divided into three groups： normal control group （CC group, db/m mice, n=8）, untreated diabetic group （DM group, db/db mice, n=8） and diabetic group treated by phlorizin （DMT group, db/db mice, n=8）. Phlorizin （20 mg/kg body weight） was given in normal saline solution intragastrically for 10 weeks. Animals were weighed weekly. At the 10th weekend, all mice were fasted overnight and then sacrificed. Fasting blood was collected, and the aortas were dissected. The blood samples were analyzed for fasting blood glucose （FBG）, serum advanced glycation end products （AGEs）, malondialdehyde （MDA） and superoxide dismutase （SOD） activity, the aortic ultrastructure was studied. Results The weight and serum concentration of FBG, AGEs, and MDA in the DM group were higher than that in the CC group （P 〈0.01 ）, and they were significantly lower in the DMT group （P 〈0.05）. Serum SOD activity was lower than that in the CC group （P 〈0.01）, and it is significantly higher in the DMT group （P 〈0.05）. The severity of aorta damage in the DMT group was less than that in the DM group. Conclusions Phlorizin protected the db/db mice from diabetic macrovascular complications, attributed to the decreasing of blood glucose and AGEs level, and its antioxidant potential. This study may provide a new natural medicine for treating diabetic macrovascular complications.展开更多
Upon glucose elevation, pancreatic beta-cells secrete insulin in a Ca2＋-dependent manner. In diabetic animal models, different aspects of the calcium signaling path- way in beta-cells are altered, but there is no con...Upon glucose elevation, pancreatic beta-cells secrete insulin in a Ca2＋-dependent manner. In diabetic animal models, different aspects of the calcium signaling path- way in beta-cells are altered, but there is no consensus regarding their relative contributions to the development of beta-cell dysfunction. In this study, we compared the increase in cytosolic Ca2＊ （[Ca2＊]~） via Ca2＋ influx, Ca2＊ mobilization from endoplasmic reticulum （ER） calcium stores, and the removal of Ca2＋ via multiple mechanisms in beta-cells from both diabetic db/db mice and non- diabetic C57BL/6J mice. We refined our previous quan- titative model to describe the slow [Ca2＋]i recovery after depolarization in beta-cells from db/db mice. According to the model, the activity levels of the two subtypes of the sarco-endoplasmic reticulum Ca2＋-ATPase （SERCA） pump, SERCA2 and SERCA3, were severely down-reg- ulated in diabetic cells to 65% and 0% of the levels in normal cells. This down-regulation may lead to a reduc- tion in the Ca2＋ concentration in the ER, a compensatory up-regulation of the plasma membrane Na＋/Ca2＋ exchanger （NCX） and a reduction in depolarizationevoked Ca2＋ influx. As a result, the patterns of glucosestimulated calcium oscillations were significantly different in db/db diabetic beta-cells compared with normal cells. Overall, quantifying the changes in the calcium signaling pathway in db/db diabetic beta-cells will aid in the development of a disease model that could provide insight into the adaptive transformations of beta-cell function during diabetes development.展开更多
基金the Program for Changjiang Scholars and Innovative Research Team in University (IRT0944)the National Natural Science Foundation of China (31070724, 30870506)+3 种基金the Special Fund for Marine Scientific Research in the Public Interest (201005024)the International Science and Technology Collaboration Program of China (2007DFA30980)the Open Research Fund of Key Laboratory of Marine Drugs of the Ministry of EducationOcean University of China (KLMD200802)
文摘Diabetes mellitus is the most common metabolic disease and its prevalence is increasing in many countries year by year.More than 90% of diabetes patients are type 2 diabetes,which is caused by insulin resistance and beta-cell dysfunction.In this paper,the oligomannuronate-chromium(III)complex(OM2)was prepared and its effect and mechanism on attenuating insulin resistance in diabetic C57BL/KsJ-db/db mice were studied.The results indicated that oral intake of OM2(50 mg kg-1d-1)for 42 d decreased blood glucose and lipid concentration,which was associated with the reduced serum insulin concentration and insulin resistance.According to western blot assay,OM2 could activate AMPK pathway to regulate glycogen synthesis,gluconeogenesis and lipid metabolism in the liver,and attenuate the hyperglycemic symptom in db/db mice.The effects of OM2 on attenuating insulin resistance were com-parable to that of the established antidiabetic drug metformin,and OM2 showed less adverse effect than metformin in vivo.Based on the effectiveness and low toxicity,OM2 may potentially be used for prevention and treatment of type 2 diabetes mellitus.
基金Supported by The Area of Excellence scheme of University Grants Committeethe Research Grant Council Grant, HKU 7642/05M to MCL, from Hong Kong
文摘AIM: To test whether oral L-81 treatment could im-prove the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetically diabetic (db/db) mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db/db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mecha-nism, HepG2 cells were treated with L-81 and the effects on apolipoprotein B (apoB) secretion and mRNA level of the MTP gene were assessed.RESULTS: Treatment of db/db mice with L-81 sig-nificantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also signif icantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter. CONCLUSION: L-81 represents a promising candidate in the development of a selective insulin-mimetic mol-ecule and an anti-diabetic agent.
文摘Background Diabetic macrovascular complications are important causes of cardiovascular and cerebrovascular diseases and also one of the major causes of morbidity and mortality in patients with type 2 diabetes mellitus （T2DM）. Phlorizin has been reported to be effective in reducing the blood glucose level in diabetic mellitus, while little is known about its effects on vascular complications. This study aimed to observe the effects of phlorizin on the aorta of diabetes db/db mice and explore its mechanism. Methods Diabetic db/db mice （n=16） and age-matched db/m mice （n=8） were divided into three groups： normal control group （CC group, db/m mice, n=8）, untreated diabetic group （DM group, db/db mice, n=8） and diabetic group treated by phlorizin （DMT group, db/db mice, n=8）. Phlorizin （20 mg/kg body weight） was given in normal saline solution intragastrically for 10 weeks. Animals were weighed weekly. At the 10th weekend, all mice were fasted overnight and then sacrificed. Fasting blood was collected, and the aortas were dissected. The blood samples were analyzed for fasting blood glucose （FBG）, serum advanced glycation end products （AGEs）, malondialdehyde （MDA） and superoxide dismutase （SOD） activity, the aortic ultrastructure was studied. Results The weight and serum concentration of FBG, AGEs, and MDA in the DM group were higher than that in the CC group （P 〈0.01 ）, and they were significantly lower in the DMT group （P 〈0.05）. Serum SOD activity was lower than that in the CC group （P 〈0.01）, and it is significantly higher in the DMT group （P 〈0.05）. The severity of aorta damage in the DMT group was less than that in the DM group. Conclusions Phlorizin protected the db/db mice from diabetic macrovascular complications, attributed to the decreasing of blood glucose and AGEs level, and its antioxidant potential. This study may provide a new natural medicine for treating diabetic macrovascular complications.
文摘Upon glucose elevation, pancreatic beta-cells secrete insulin in a Ca2＋-dependent manner. In diabetic animal models, different aspects of the calcium signaling path- way in beta-cells are altered, but there is no consensus regarding their relative contributions to the development of beta-cell dysfunction. In this study, we compared the increase in cytosolic Ca2＊ （[Ca2＊]~） via Ca2＋ influx, Ca2＊ mobilization from endoplasmic reticulum （ER） calcium stores, and the removal of Ca2＋ via multiple mechanisms in beta-cells from both diabetic db/db mice and non- diabetic C57BL/6J mice. We refined our previous quan- titative model to describe the slow [Ca2＋]i recovery after depolarization in beta-cells from db/db mice. According to the model, the activity levels of the two subtypes of the sarco-endoplasmic reticulum Ca2＋-ATPase （SERCA） pump, SERCA2 and SERCA3, were severely down-reg- ulated in diabetic cells to 65% and 0% of the levels in normal cells. This down-regulation may lead to a reduc- tion in the Ca2＋ concentration in the ER, a compensatory up-regulation of the plasma membrane Na＋/Ca2＋ exchanger （NCX） and a reduction in depolarizationevoked Ca2＋ influx. As a result, the patterns of glucosestimulated calcium oscillations were significantly different in db/db diabetic beta-cells compared with normal cells. Overall, quantifying the changes in the calcium signaling pathway in db/db diabetic beta-cells will aid in the development of a disease model that could provide insight into the adaptive transformations of beta-cell function during diabetes development.
