Background Glucolipotoxicity might play an important role in the β cell decompensation stage during the development of obesity-associated type 2 diabetes.Tissue inhibitor of metalloproteinase-1 （TIMP-1） inhibits ma...Background Glucolipotoxicity might play an important role in the β cell decompensation stage during the development of obesity-associated type 2 diabetes.Tissue inhibitor of metalloproteinase-1 （TIMP-1） inhibits matrix metalloproteinase （MMP） activity and regulates proliferation and apoptosis of a variety of cell types,including pancreatic β-cells.In the present study,we investigated whether TIMP-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1.Methods INS-1 cells were incubated in normal or high glucose,with or without palmitate （0.4 mmol/L）,in the presence of TIMP-1 or MMP inhibitor GM60001.In some experiments,cells were pretreated with phosphatidylinositol-3 （Pl-3） kinase inhibitor,LY294002 or wortmannin.The amount of dead INS-1 cells was determined by HO342 and propidium iodide staining.Akt phosphorylation was evaluated by Western blotting analysis to investigate a possible mechanism of TIMP-1＇s action.Results TIMP-1 protected INS-1 cells from glucolipotoxicity independent of MMP inhibition.TIMP-1 stimulated Akt phosphorylation.Inhibition of the PI-3 kinase pathway abolished the survival effect of TIMP-1.Conclusion TIMP-1 may counteract glucolipotoxicity induced β-cell death via a PI-3 kinase pathway.展开更多
Glucolipotocixity induces IL-1βsecretion which impairs pancreaticβ-cell insulin secretion.Ellagic acid and urolithin A have strong anti-inflammatory effect on cells.Muscadine and amla are very good sources of ellagi...Glucolipotocixity induces IL-1βsecretion which impairs pancreaticβ-cell insulin secretion.Ellagic acid and urolithin A have strong anti-inflammatory effect on cells.Muscadine and amla are very good sources of ellagic acid.The present study examined the effect of ellagic acid,ellagic acid-rich muscadine or amla extract,or urolothin A on inflammation inβcells under glucolipotoxic conditions.Rat NIT-1βcells were incubated in glucolipotoxic conditions(33.3 mM glucose,250μM palmitic acid or 33.3 mM glucose+250μM palmitic acid with or without ellagic acid,ellagic acid-rich muscadine or amla extracts standardized to its ellagic acid content,or urolithin A).Inflammatory status was evidenced by ELISA analysis of insulin and IL-1βsecretion.Ellagic acid-rich muscadine or amla extracts dose-dependently stimulated insulin secretion and down-regulated IL-1βbetter than pure ellagic acid,or urolithin A.Urolithin A did not statistically stimulate insulin secretion and did not inhibit IL-1β.展开更多
Medical therapy for type 2 diabetes mellitus is ineffective in the long term due to the progressive nature of the disease, which requires increasing medication doses and polypharmacy. Conversely, bariatric surgery has...Medical therapy for type 2 diabetes mellitus is ineffective in the long term due to the progressive nature of the disease, which requires increasing medication doses and polypharmacy. Conversely, bariatric surgery has emerged as a cost-effective strategy for obese diabetic individuals; it has low complication rates and results in durable weight loss, glycemic control and improvements in the quality of life, obesity-related co-morbidity and overall survival. The finding that glucose homeostasis can be achieved with a weight loss-independent mechanism immediately after bariatric surgery, especially gastric bypass, has led to the paradigm of metabolic surgery. However, the primary focus of metabolic surgery is the alteration of the physio-anatomy of the gastrointestinal tract to achieve glycemic control, metabolic control and cardio-metabolic risk reduction. To date, metabolic surgery is still not well defined, as it is used most frequently for less obese patients with poorly controlled diabetes. The mechanism of glycemic control is still incompletely understood. Published research findings on metabolic surgery are promising, but many aspects still need to be defined. This paper examines the proposed mechanism of diabetes remission, the efficacy of different types of metabolic procedures, the durability of glucose control, and the risks and complications associated with this procedure. We propose a tailored approach for the selection of the ideal metabolic procedure for different groups of patients, considering the indications and prognostic factors for diabetes remission.展开更多
文摘Background Glucolipotoxicity might play an important role in the β cell decompensation stage during the development of obesity-associated type 2 diabetes.Tissue inhibitor of metalloproteinase-1 （TIMP-1） inhibits matrix metalloproteinase （MMP） activity and regulates proliferation and apoptosis of a variety of cell types,including pancreatic β-cells.In the present study,we investigated whether TIMP-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1.Methods INS-1 cells were incubated in normal or high glucose,with or without palmitate （0.4 mmol/L）,in the presence of TIMP-1 or MMP inhibitor GM60001.In some experiments,cells were pretreated with phosphatidylinositol-3 （Pl-3） kinase inhibitor,LY294002 or wortmannin.The amount of dead INS-1 cells was determined by HO342 and propidium iodide staining.Akt phosphorylation was evaluated by Western blotting analysis to investigate a possible mechanism of TIMP-1＇s action.Results TIMP-1 protected INS-1 cells from glucolipotoxicity independent of MMP inhibition.TIMP-1 stimulated Akt phosphorylation.Inhibition of the PI-3 kinase pathway abolished the survival effect of TIMP-1.Conclusion TIMP-1 may counteract glucolipotoxicity induced β-cell death via a PI-3 kinase pathway.
文摘Glucolipotocixity induces IL-1βsecretion which impairs pancreaticβ-cell insulin secretion.Ellagic acid and urolithin A have strong anti-inflammatory effect on cells.Muscadine and amla are very good sources of ellagic acid.The present study examined the effect of ellagic acid,ellagic acid-rich muscadine or amla extract,or urolothin A on inflammation inβcells under glucolipotoxic conditions.Rat NIT-1βcells were incubated in glucolipotoxic conditions(33.3 mM glucose,250μM palmitic acid or 33.3 mM glucose+250μM palmitic acid with or without ellagic acid,ellagic acid-rich muscadine or amla extracts standardized to its ellagic acid content,or urolithin A).Inflammatory status was evidenced by ELISA analysis of insulin and IL-1βsecretion.Ellagic acid-rich muscadine or amla extracts dose-dependently stimulated insulin secretion and down-regulated IL-1βbetter than pure ellagic acid,or urolithin A.Urolithin A did not statistically stimulate insulin secretion and did not inhibit IL-1β.
文摘Medical therapy for type 2 diabetes mellitus is ineffective in the long term due to the progressive nature of the disease, which requires increasing medication doses and polypharmacy. Conversely, bariatric surgery has emerged as a cost-effective strategy for obese diabetic individuals; it has low complication rates and results in durable weight loss, glycemic control and improvements in the quality of life, obesity-related co-morbidity and overall survival. The finding that glucose homeostasis can be achieved with a weight loss-independent mechanism immediately after bariatric surgery, especially gastric bypass, has led to the paradigm of metabolic surgery. However, the primary focus of metabolic surgery is the alteration of the physio-anatomy of the gastrointestinal tract to achieve glycemic control, metabolic control and cardio-metabolic risk reduction. To date, metabolic surgery is still not well defined, as it is used most frequently for less obese patients with poorly controlled diabetes. The mechanism of glycemic control is still incompletely understood. Published research findings on metabolic surgery are promising, but many aspects still need to be defined. This paper examines the proposed mechanism of diabetes remission, the efficacy of different types of metabolic procedures, the durability of glucose control, and the risks and complications associated with this procedure. We propose a tailored approach for the selection of the ideal metabolic procedure for different groups of patients, considering the indications and prognostic factors for diabetes remission.
