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:Insulin resistance increases patient’s risk of developing type 2 diabetes (T2D), nonalcoholic steatohepatitis (NASH) and a host of other comorbidities including cardiovascular disease and cancer. At the molecular level, insulin exerts its function through the insulin receptor (IR), a transmembrane receptor tyrosine kinase. Data from human genetic studies have shown that Grb14 functions as a negative modulator of IR activity, and germline Grb14-knockout (KO) mice have improved insulin signaling in liver and muscle tissues. Here, we show that Grb14 knockdown in the liver and the heart with an AAV-shRNA (Grb14-shRNA) improves glucose homeostasis in diet-induced obese (DIO) mice. A previous report has shown that germline deletion of Grb14 in mice results in cardiac hypertrophy and decreased systolic function, effects that could severely limit the therapeutic potential of targeting Grb14. In this report, we demonstrate that there are no significant changes in hemodynamic function as measured by echocardiography in DIO Grb14 and DIO sham mice for a period of four months. While additional studies are needed to further establish efficacy and to de-risk potential negative cardiac effects in pre-clinical heart failure models, our data support inhibiting Grb14 to treat diabetes and related conditions.
Project description:Bezafibrate (BEZ), a pan activator of peroxisome proliferator-activated receptors (PPARs), is generally used to treat hyperlipidemia. Clinical trials on patients suffering from type 2 diabetes indicated that BEZ also has beneficial effects on glucose metabolism, but the underlying mechanisms remain elusive. Much less is known about the function of BEZ in type 1 diabetes. Here, we show that BEZ treatment markedly improves hyperglycemia, glucose and insulin tolerance in streptozotocin (STZ)-treated mice, an insulin-deficient mouse model of type 1 diabetes presenting with very high blood glucose levels. Furthermore, BEZ-treated mice also exhibited improved metabolic flexibility as well as an enhanced mitochondrial mass and function in the liver. Our data demonstrate a beneficial effect of BEZ treatment on STZ mice reducing diabetes and suggest that BEZ ameliorates impaired glucose metabolism possibly via augmented hepatic mitochondrial performance, improved insulin sensitivity and metabolic flexibility. We performed gene expression microarray analysis on liver tissue derived from streptozotocin-treated mice treated with bezafibrate in addition.
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: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:Bezafibrate (BEZ), a pan activator of peroxisome proliferator-activated receptors (PPARs), is generally used to treat hyperlipidemia. Clinical trials on patients suffering from type 2 diabetes indicated that BEZ also has beneficial effects on glucose metabolism, but the underlying mechanisms remain elusive. Much less is known about the function of BEZ in type 1 diabetes. Here, we show that BEZ treatment markedly improves hyperglycemia, glucose and insulin tolerance in streptozotocin (STZ)-treated mice, an insulin-deficient mouse model of type 1 diabetes presenting with very high blood glucose levels. Furthermore, BEZ-treated mice also exhibited improved metabolic flexibility as well as an enhanced mitochondrial mass and function in the liver. Our data demonstrate a beneficial effect of BEZ treatment on STZ mice reducing diabetes and suggest that BEZ ameliorates impaired glucose metabolism possibly via augmented hepatic mitochondrial performance, improved insulin sensitivity and metabolic flexibility.