YiQi YangYin Decoction Attenuates Nonalcoholic Fatty Liver Disease in Type 2 Diabetes Rats

Background. YiQi YangYin Decoction (YQ) is a modern Chinese formula composed by the guidance of traditional Chinese medicine theory, which consists of nine traditional Chinese medicines and is applied to treat type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver in clinic in China for more than a decade. This study aims to evaluate the antidiabetes and lipid-lowering effect of YQ and explore the possible mechanisms of this action. Methods. T2DM rat models were established and given YQ at three different doses for three weeks. Tissues, including pancreas islet and liver, and blood serum were collected. The levels of fasting blood glucose (FBG), fasting insulin (Fins), lipid index, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), and hepatic function index such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in serum were measured. Pancreas islet damage and liver damage were observed by hematoxylin and eosin staining. The glycogen content and lipid accumulation in liver were determined by periodic acid-Schiff (PAS) staining and Oil Red O staining. The expression levels of insulin receptor substrate 2 (IRS-2), phosphatidylinositol 3 kinase-associated p85alpha (PI3K p85α), AKT, and Glucose Transporter 2 (Glut4) in pancreas islet and AMP-activated protein kinase alpha (AMPKα), sterol regulatory element-binding protein 1c (SREBP1c), acetyl-CoA carboxylase (ACC1), and peroxisome proliferator‐activated receptor-α (PPARα) in liver were determined by western blotting. The relative expressions of ACC1, fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1), carnitine palmityl transferase-1 (CPT-1), and SREBP-1 mRNA were detected by qRT-PCR. Results. After administering YiQi for three weeks, the levels of fast blood glucose, fasting insulin, TC, TG, LDL, ALT, AST, and ALP were significantly decreased, while HDL significantly increased compared with the model group. YQ could obviously attenuate pancreatic damage and improve islet α- and ß-cell survival compared with the model group. Furthermore, YQ could attenuate hepatic damage caused by lipid accumulation, decrease the content of lipid, and increase the hepatic glycogen content, compared with the model group. In addition, YQ remarkably elevated the proteins expression of p-PI3K, p-AKT, and GLUT4 in pancreas islet and elevated the proteins expression of p-PI3K, p-AKT, GLUT4, p-AMPK, SREBP1, and PPARα and inhibited the expression of p-ACC1 in liver. Besides, YQ reduced the relative expression of ACC1, FAS, SERBP-1c, and SCD mRNA along with the decreased production of CPT-1 mRNA. Conclusions. YQ could attenuate type 2 diabetes mellitus by improving islet α- and ß-cells via IRS-2/AKT/GLUT4 pathway and nonalcoholic fatty liver by ameliorating lipid accumulation via AMPK/PPARα/SREBP1/ACC1 pathway.

Pancreas-Brain Crosstalk

The neural regulation of glucose homeostasis in normal and challenged conditions involves the modulation of pancreatic islet-cell function. Compromising the pancreas innervation causes islet autoimmunity in type 1 diabetes and islet cell dysfunction in type 2 diabetes. However, despite the richly innervated nature of the pancreas, islet innervation remains ill-defined. Here, we review the neuroanatomical and humoral basis of the cross-talk between the endocrine pancreas and autonomic and sensory neurons. Identifying the neurocircuitry and neurochemistry of the neuro-insular network would provide clues to neuromodulation-based approaches for the prevention and treatment of diabetes and obesity.

Identification of MEDAG as a Hub Candidate Gene in the Onset and Progression of Type 2 Diabetes Mellitus by Comprehensive Bioinformatics Analysis

Objectives. We conducted the present study to identify novel hub candidate genes in the pathogenesis of type 2 diabetes mellitus (T2DM) and provide potential biomarkers or therapeutic targets for dealing with the disease. Methods. We conducted weighted gene coexpression network analysis on a series of the expression profiles of the pancreas islet of T2DM patients obtained from the Gene Expression Omnibus database to construct a weighted coexpression network. After dividing genes into separated coexpression modules, we identified a T2DM-related module using Pearson’s correlation analysis. Then, hub genes were identified from the T2DM-related module using the Maximal Clique Centrality method and validated by correlation analysis with clinical traits, differentially expressed gene analysis, validation in other datasets, and single-gene gene set enrichment analysis (GSEA). Results. Genes were divided into 16 coexpression modules, and one module was identified as a T2DM-related module. Four hub candidate genes were identified, and MEDAG was a novel hub candidate gene. The expression level of MEDAG was positively correlated with hemoglobin A1c (HbA1c) and was evidently overexpressed in the pancreas islet tissue of T2DM patients compared with normal control. Analyses on two other datasets supported the results. GSEA verified that MEDAG plays essential roles in T2DM. Conclusions. MEDAG is a novel hub candidate of T2DM, and its irregular expression in the pancreas islet plays vital roles in the pathogenesis of T2DM. MEDAG is a potential target of intervention in the future for the treatment of T2DM.

Duodenal gangliocytic paraganglioma: a rare case report

Background Gangliocytic paraganglioma (GP) is quite rare, and origin and entity remain to be elucidated. Case presentation A 51-year-old male presented with a sessile polyp with smooth surface measured about 1cm in diameter in the descending portion of duodenum. Pathological examination displayed a neoplasm located in submucosa, infiltrating into lamina propria. The tumor consisted of epithelioid, ganglion-like and spindle cells admixing in a haphazard way. The epithelioid cells resembled paraganglioma in cytological and architectural features, the ganglion-like cells was scattered, and the spindle cells resembled neurofibroma. Syn, MAP-2 and CgA were positive in the epithelioid and ganglion-like cells in variety and NF highlighted the ganglion-like cells. S-100 and SOX-10 were positive in the sustentacular cells around the epithelioid cells and spindle cell proliferation. PR was also positive. Conclusions Origin of GP is presumed to be related with pancreas islet. GP is supposed to be distinguished with NET G1 and designated as paraganglioma-ganglioneuroma, a kind of composite paraganglioma.