Project description:The incidence of type 2 diabetes (T2DM) induced by obesity is rapidly increasing. Although there are many drugs developed for type 2 diabetes, but the anti-diabetic effect of homology of medicine and food is also very popular with the majority of people. Burdock is one such food, but the molecular mechanism of anti-diabetic effect is unclear, limiting its further promotion. In recent years, studies have shown that plant mirnas can regulate host gene expression through dietary absorption, so plant miRNAs have become one of the main active ingredients in traditional Chinese medicine. Here, we report that miR8175, a plant miRNA from burdock root, has effective antidiabetic activity. miR8175 is highly enriched in burdock decoction. After administration of burdock decoction or synthetic miR8175 by gavage, significantly elevated levels of miR8175 in mouse serum and liver can be observed. Furthermore, both burdock decoction and miR8175 can significantly improve the impaired glucose metabolism of diabetic mice induced by a high-fat diet (HFD). Our results demonstrate that burdock decoction and miR8175 enhance the insulin sensitivity of the hepatic insulin signaling pathway by targeting PTPRF and PTP1B, which may be the reason for the improvement in metabolism.
Project description:The incidence of type 2 diabetes (T2DM) induced by obesity is rapidly increasing. Although there are many drugs developed for type 2 diabetes, but the anti-diabetic effect of homology of medicine and food is also very popular with the majority of people. Burdock is one such food, but the molecular mechanism of anti-diabetic effect is unclear, limiting its further promotion. In recent years, studies have shown that plant mirnas can regulate host gene expression through dietary absorption, so plant miRNAs have become one of the main active ingredients in traditional Chinese medicine. Here, we report that miR8175, a plant miRNA from burdock root, has effective antidiabetic activity. miR8175 is highly enriched in burdock decoction. After administration of burdock decoction or synthetic miR8175 by gavage, significantly elevated levels of miR8175 in mouse serum and liver can be observed. Furthermore, both burdock decoction and miR8175 can significantly improve the impaired glucose metabolism of diabetic mice induced by a high-fat diet (HFD). Our results demonstrate that burdock decoction and miR8175 enhance the insulin sensitivity of the hepatic insulin signaling pathway by targeting PTPRF and PTP1B, which may be the reason for the improvement in metabolism.
Project description:The incidence of type 2 diabetes (T2DM) induced by obesity is rapidly increasing. Although there are many drugs developed for type 2 diabetes, but the anti-diabetic effect of homology of medicine and food is also very popular with the majority of people. Burdock is one such food, but the molecular mechanism of anti-diabetic effect is unclear, limiting its further promotion. In recent years, studies have shown that plant mirnas can regulate host gene expression through dietary absorption, so plant miRNAs have become one of the main active ingredients in traditional Chinese medicine. Here, we report that miR8175, a plant miRNA from burdock root, has effective antidiabetic activity. miR8175 is highly enriched in burdock decoction. After administration of burdock decoction or synthetic miR8175 by gavage, significantly elevated levels of miR8175 in mouse serum and liver can be observed. Furthermore, both burdock decoction and miR8175 can significantly improve the impaired glucose metabolism of diabetic mice induced by a high-fat diet (HFD). Our results demonstrate that burdock decoction and miR8175 enhance the insulin sensitivity of the hepatic insulin signaling pathway by targeting PTPRF and PTP1B, which may be the reason for the improvement in metabolism.
Project description:Background: The prevalence of type 2 diabetes has increased dramatically in recent decades. Increasing brown adipose tissue (BAT) mass and activity has recently emerged as an interesting approach to not only increase energy expenditure, but also improve glucose homeostasis. BAT can be recruited by prolonged cold exposure in lean, healthy humans. Here, we tested whether cold acclimation could have therapeutic value for patients with type 2 diabetes by improving insulin sensitivity. Methods: Eight type 2 diabetic patients (age 59.3±5.8 years, BMI 29.8±3.2 kg/m2) followed a cold acclimation protocol, consisting of intermittent cold exposure (6 hours/day, 14-14.5 °C) for 12 consecutive days. Before and after cold acclimation, cold-induced BAT activity was assessed by [18F]FDG-PET/CT scanning, insulin sensitivity at thermoneutrality by a hyperinsulinemic-euglycemic clamp, and muscle and WAT biopsies were taken. Results: Cold-induced BAT activity was low, but increased in all patients upon cold acclimation (SUV from 0.40±0.29 to 0.63±0.78, p<0.05). Interestingly, insulin sensitivity showed a very pronounced 40% increase upon cold acclimation (glucose rate of disappearance from 14.9±4.1 to 20.5±6.9 μmol kg-1 min-1, p<0.05). A 40% increase in insulin sensitivity cannot be explained by BAT glucose uptake, in fact basal skeletal muscle GLUT4 content and translocation was markedly increased after cold acclimation, without effects on insulin signaling or AMPk activation. Conclusions: Regular mild cold exposure has marked effects on insulin sensitivity, which are accompanied by small increases in BAT activity and more pronounced effects on skeletal muscle. These data suggest a novel therapeutic option for the treatment of type 2 diabetes. Microarray analysis was performed on abdominal subcutaneous white adipose tissue samples from human type 2 diabetic patients before, and after 10 days of cold acclimation. A total of 14 samples, from 7 subjects, were used for the microarray analysis.
Project description:Type 2 diabetes is characterized by excessive lipid storage in skeletal muscle. Excessive intramyocellular lipid storage exceeds intracellular needs and induces lipotoxic events ultimately contributing to the development of insulin resistance. Lipid droplet (LD)-coating proteins may control proper lipid storage in skeletal muscle. Perilipin 2 (PLIN2/ADRP) is one of the most abundantly expressed LD-coating proteins in skeletal muscle. Here we examined the role of PLIN2 in myocellular lipid handling and insulin sensitivity by investigating the effects of in vitro PLIN2 knockdown and in vitro and in vivo overexpression. PLIN2 knockdown decreased LD formation and triacylglycerol storage, marginally increased FA oxidation, and increased incorporation of palmitate into diacylglycerols and phospholipids. PLIN2 overexpression in vitro increased intramyocellular TAG storage paralleled with improved insulin sensitivity. In vivo muscle-specific PLIN2 overexpression resulted in increased LD accumulation and blunted the high-fat diet-induced increase of OXPHOS protein content. Diacylglycerol levels were unchanged, while ceramide levels were increased. Despite the increased intramyocellular lipid accumulation, PLIN2 overexpression improved skeletal muscle insulin sensitivity. We conclude that PLIN2 is essential for lipid storage in skeletal muscle by enhancing the partitioning of excess FAs towards triacylglycerol storage in LDs thereby blunting lipotoxicity-associated insulin resistance. C2C12 cells (mouse myoblast cell line) were treated with fatty acids and effects of knockdown of Perilipin 2 by siRNA were studied by gene expression profiling.
Project description:Analysis of protein tyrosine phosphatase 1B (PTP1B) deficient mammary glands from nulliparous mice at estrous and pregnancy day 3, 7, 10 and 15. We used a genetically ablated PTP1B mouse model to gain a deeper knowledge of the role PTP1B plays in mammary gland development and to define the mechanism regulated by this phosphatase. Results provide insight into the role of PTP1B in mammary gland development and differentiation. Mouse mammary glands were isolated from PTP1B -/- and PTP1B +/+ nulliparous mice at estrous and pregnancy day 3, 7, 10 and 15 for RNA extraction and hybridization on Affymetrix microarrays.
Project description:Background: The prevalence of type 2 diabetes has increased dramatically in recent decades. Increasing brown adipose tissue (BAT) mass and activity has recently emerged as an interesting approach to not only increase energy expenditure, but also improve glucose homeostasis. BAT can be recruited by prolonged cold exposure in lean, healthy humans. Here, we tested whether cold acclimation could have therapeutic value for patients with type 2 diabetes by improving insulin sensitivity. Methods: Eight type 2 diabetic patients (age 59.3±5.8 years, BMI 29.8±3.2 kg/m2) followed a cold acclimation protocol, consisting of intermittent cold exposure (6 hours/day, 14-14.5 °C) for 12 consecutive days. Before and after cold acclimation, cold-induced BAT activity was assessed by [18F]FDG-PET/CT scanning, insulin sensitivity at thermoneutrality by a hyperinsulinemic-euglycemic clamp, and muscle and WAT biopsies were taken. Results: Cold-induced BAT activity was low, but increased in all patients upon cold acclimation (SUV from 0.40±0.29 to 0.63±0.78, p<0.05). Interestingly, insulin sensitivity showed a very pronounced 40% increase upon cold acclimation (glucose rate of disappearance from 14.9±4.1 to 20.5±6.9 μmol kg-1 min-1, p<0.05). A 40% increase in insulin sensitivity cannot be explained by BAT glucose uptake, in fact basal skeletal muscle GLUT4 content and translocation was markedly increased after cold acclimation, without effects on insulin signaling or AMPk activation. Conclusions: Regular mild cold exposure has marked effects on insulin sensitivity, which are accompanied by small increases in BAT activity and more pronounced effects on skeletal muscle. These data suggest a novel therapeutic option for the treatment of type 2 diabetes.