Jinhua Yan

Berberine Improves Glucose Metabolism in Diabetic Rats by Inhibition of Hepatic Gluconeogenesis

Berberine (BBR) is a compound originally identified in a Chinese herbal medicine Huanglian (Coptis chinensis French). It improves glucose metabolism in type 2 diabetic patients. The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK) and improvement of insulin sensitivity. However, it is not clear if BBR reduces blood glucose through other mechanism. In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyperglycemia was induced in Sprague-Dawley rats by high fat diet. We observed that BBR decreased fasting glucose significantly. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase), were decreased in liver by BBR. Hepatic steatosis was also reduced by BBR and expression of fatty acid synthase (FAS) was inhibited in liver. Activities of transcription factors including Forkhead transcription factor O1 (FoxO1), sterol regulatory element-binding protein 1c (SREBP1) and carbohydrate responsive element-binding protein (ChREBP) were decreased. Insulin signaling pathway was not altered in the liver. In cultured hepatocytes, BBR inhibited oxygen consumption and reduced intracellular adenosine triphosphate (ATP) level. The data suggest that BBR improves fasting blood glucose by direct inhibition of gluconeogenesis in liver. This activity is not dependent on insulin action. The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR. The observation supports that BBR improves glucose metabolism through an insulin-independent pathway.

Comparison of the effects on glycaemic control and β‐cell function in newly diagnosed type 2 diabetes patients of treatment with exenatide, insulin or pioglitazone: a multicentre randomized parallel‐group trial (the CONFIDENCE study)

Progressive β‐cell dysfunction hinders the maintenance of glycaemic control in type 2 diabetes, but comparative data on β‐cell‐protective therapies are lacking in the early stage of type 2 diabetes. Here we evaluated the comparative glycaemic efficacy and impact on β‐cell function of three antihyperglycaemic agents that have a β‐cell‐protective effect, exenatide, insulin and pioglitazone, in newly diagnosed patients with type 2 diabetes.

Secondary diabetic ketoacidosis and severe hypoglycaemia in patients with established type 1 diabetes mellitus in China: a multicentre registration study

Diabetic ketoacidosis (DKA) and severe hypoglycaemia are common acute complications of type 1 diabetes mellitus (T1DM). This study aimed to determine the incidence of, and risk factors for, these complications in Chinese patients with established T1DM.

Association of β-cell function and insulin sensitivity with fasting and 2-h plasma glucose in a large Chinese population.

Aim: Our aim was to provide a quantitative analysis of the changes in the principal determinants of insulin sensitivity and secretion in relation to fasting plasma glucose (FPG) or 2‐h plasma glucose (2h PG) in a Chinese population with a wide range of glucose tolerance.

Glycemic variability is an important risk factor for cardiovascular autonomic neuropathy in newly diagnosed type 2 diabetic patients.

BACKGROUND The relationship between glycemic variability, another component of glycemic disorders as well as chronic sustained hyperglycemia, and cardiovascular autonomic neuropathy (CAN) has not been clarified. Our aim is to investigate the association between glycemic variability and CAN in newly diagnosed type 2 diabetic patients. METHODS Ewing tests were performed in 90 newly diagnosed type 2 diabetic patients and 37 participants with normal glucose tolerance as control from May 1, 2009, through September 30, 2010. According to the scores from Ewing tests, diabetic patients were divided into two groups: without CAN (CAN-) and with CAN (CAN+). All participants underwent a 48-h to 72-h continuous glucose monitoring (CGM). Coefficient of variability of glycemia (%CV), mean amplitude of glycemic excursions (MAGE) and means of daily differences (MODD) were calculated with the CGM data. RESULTS The prevalence of CAN in patients with newly diagnosed type 2 diabetes was 22.2%. An increasing trend of glycemic variability was found from control group, CAN- group to CAN+ group. MAGE in CAN+ group was significantly higher than that in CAN- group (5.27±1.99mmol/L vs. 4.04±1.39mmol/L, P=0.001). In the Logistic regression analysis, a significant relationship was shown between MAGE and CAN [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.01-2.73, P=0.018)]. The area under the receiver-operating characteristic curve for MAGE was superior to those for other dysglycemic indices in detecting CAN. CONCLUSIONS Glycemic variability is associated with CAN in patients with newly diagnosed type 2 diabetes. Among the glycemic variability indices, MAGE is a significant indicator for detecting CAN.

Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin‑induced diabetes in miniature pigs: Real‑time tracing with MRI in vivo

Cellular replacement therapy for diabetes mellitus (DM) has received much attention. In this study, we investigated the effect of transplantation of autologous bone marrow-derived mesenchymal stem cells (ABMSCs) in streptozotocin (STZ)-induced diabetic miniature pigs. Miniature pig BMSCs were cultured, labeled with superparamagnetic iron oxide (SPIO) and transplanted into the pancreas of diabetic miniature pigs through targeted intervention. Blood glucose levels, intravenous and oral glucose tolerance test (OGTT), serum insulin, C-peptide and islets histology were analyzed. These transplanted cells were then identified by magnetic resonance imaging (MRI). The results showed that transplantation of ABMSCs reversed STZ-induced diabetes in miniature pigs. Blood glucose levels, intravenous, OGTT, serum insulin and C-peptide were significantly recovered in the diabetic minipigs with the autologous BMSC (DMAB) transplantation group. In addition, the number of islets was significantly increased in this group compared to the diabetic minipig control (DMC) group with conventional therapy. These data suggested the implantation of autologous BMSCs for type 1 diabetes treatment can partially restore the function of islet β cells and maintain blood glucose homeostasis. Transplanted autologous BMSCs may improve islet repairing by differentiating for new islets and change pancreatic microcirculation and be identified in a real-time manner using MRI in vivo.

GLP-1 Receptor Agonist Exenatide Attenuates the Detrimental Effects of Obesity on Inflammatory Profile in Testis and Sperm Quality in Mice.

Male obesity has been linked to subfecundity. This study is to investigate the effects of GLP‐1 receptor (GLP‐1R) agonist exenatide on sperm quality in high‐fat diet (HFD)‐induced obese mice.

The SRE Motif in the Human PNPLA3 Promoter (-97 to -88 bp) Mediates Transactivational Effects of SREBP-1c.

Patatin‐like phospholipase domain containing 3 (PNPLA3) is a non‐secreted protein primarily expressed in liver and adipose tissue. Recently, numerous genetic studies have shown that PNPLA3 is a major susceptibility gene for nonalcoholic fatty liver disease (NAFLD). However, the mechanism involved in transcriptional regulation of the PNPLA3 gene remains unknown. We performed a detailed analysis of the human PNPLA3 gene promoter and identified two novel cis‐acting elements (SRE and NFY binding motifs) located at −97/−88 and −26/−22 bp, respectively. Overexpression of SREBP‐1c in HepG2 cells significantly increased PNPLA3 promoter activity. Mutation of either of the putative SRE or NFY binding motifs blocked the transactivation effects of SREBP‐1c on the promoter. Overexpression of SREBP‐1c and NFY together increased PNPLA3 promoter activity twice as much as that of SREBP‐1c or NFY expression alone. This result suggests that SREBP‐1c and NFY synergistically transactivate the human PNPLA3 gene. The ability of SREBP‐1c and NFY to bind these cis‐elements was confirmed using gel shift analysis. Putative SRE and NFY motifs also mediated synergistic insulin‐induced transactivation of the PNPLA3 promoter in HepG2 cells. Additionally, the ability of SREBP‐1c to bind to the PNPLA3 promoter was increased by insulin in a dose‐dependent manner. Moreover, the treatment of HepG2 cells with the PI3K inhibitor LY294002 led to reduced insulin promoter‐activating ability accompanied by a decrease in PNPLA3 and SREBP‐1c protein expression. These results demonstrate that SREBP‐1c is a direct activator of the human PNPLA3 gene and insulin transactivates the PNPLA3 gene via the PI3K‐SREBP‐1c/NFY pathway in HepG2 cells. J. Cell. Physiol. 230: 2224–2232, 2015.

Glycaemic control and its associated factors in Chinese adults with type 1 diabetes mellitus.

Glycaemic control is a great challenge in the management of type 1 diabetes mellitus (T1DM). There is limited data concerning glycaemic control among adults with T1DM. We used data from the Guangdong T1DM Translational Medicine Study to evaluate glycaemic control and its associated factors in Chinese adults with T1DM.

Demographic and clinical characteristics of patients with type 1 diabetes mellitus: a multicenter registry study in Guangdong, China.

A lack of demographic and clinical data hinders efforts of health care providers in China to support patients with type 1 diabetes mellitus (T1D). Therefore, the aim of the present retrospective study was to provide an overview of the demographic and clinical characteristics of Chinese patients with T1D.