Xuemei Gu

Phycocyanin protects INS-1E pancreatic beta cells against human islet amyloid polypeptide-induced apoptosis through attenuating oxidative stress and modulating JNK and p38 mitogen-activated protein kinase pathways

It is widely accepted that human islet amyloid polypeptide (hIAPP) aggregation plays an important role in the loss of insulin-producing pancreatic beta cells. hIAPP-induced cytotoxicity is mediated by generation of reactive oxygen species (ROS). Phycocyanin (PC) is a natural compound from blue-green algae that is widely used as food supplement. Currently, little is known about the effects of PC on beta cells with the presence of hIAPP. The aim of this study was to investigate the in vitro protective effects of PC on INS-1E rat insulinoma beta cells against hIAPP-induced cell death, as well as the underlying mechanisms. Our results showed that hIAPP-induced cell death with apoptotic characteristics including growth inhibition, chromatin condensation and DNA fragmentation. However, cytotoxicity of hIAPP was significantly attenuated by co-incubation of the cells with PC. The results of Western blotting showed that activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP) in hIAPP-treated cells was blocked by PC. Moreover, PC significantly prevented the hIAPP-induced overproduction of intracellular ROS and malondialdehyde (MDA), as well as changes in activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes. Furthermore, hIAPP triggered the activation of mitogen-activated protein kinases (MAPKs), and these effects were effectively suppressed by PC. Taken together, our results suggest that PC protects INS-1E pancreatic beta cells against hIAPP-induced apoptotic cell death through attenuating oxidative stress and modulating c-Jun N-terminal kinase (JNK) and p38 pathways.

Exendin-4 protects pancreatic beta cells from human islet amyloid polypeptide-induced cell damage: potential involvement of AKT and mitochondria biogenesis.

Aim: Glucagon‐like peptide‐1 (GLP‐1) stimulates beta‐cell proliferation and enhances beta‐cell survival, whereas oligomerization of human islet amyloid polypeptide (hIAPP) may induce beta‐cell apoptosis and reduce beta‐cell mass. Type 2 diabetes is associated with increased expression of IAPP. As GLP‐1‐based therapy is currently developed as a novel antidiabetic therapy, we examined the potential protective action of the GLP‐1 receptor agonist exendin‐4 on hIAPP‐induced beta‐cell apoptosis.

Bip overexpression, but not CHOP inhibition, attenuates fatty-acid-induced endoplasmic reticulum stress and apoptosis in HepG2 liver cells

AIMSnIn this study we investigated whether attenuation of endoplasmic reticulum stress (ER stress) could protect HepG2 cells from free fatty acid (FFA)-induced apoptosis.nnnMAIN METHODSnHuman liver cell line HepG2 cells were exposed to Sodium Palmitate (Pa) or Sodium Oleate (Ol). Apoptosis and ER stress of HepG2 cells were analyzed with flow cytometry, real-time RT-PCR and Western Blotting. An expression plasmid encoding for the ER chaperone immunoglobulin heavy chain-binding protein (Bip) was transfected into HepG2 cells to attenuate ER stress. Small interfering RNA siCHOP was used to knockdown the expression of C/EBP Homologous Protein (CHOP) in HepG2.nnnKEY FINDINGSnPa led to cytotoxicity and apoptosis in HepG2 cells in a dose-dependent pattern and also induced ER stress indicated by increased phosphorylation of eIF2α, upregulation of IRE1α and CHOP. Bip expression levels were slightly down regulated after Pa treatment. The unsaturated fatty acid, Ol, induced neither apoptosis nor ER stress in HepG2 cells. Overexpression of Bip attenuated Pa-induced ER stress and led to a significant reduction in Pa-mediated apoptosis, indicating a requirement of ER stress for lipotoxicity in liver cells. siRNA-mediated reduction of CHOP did not protect against Pa-induced apoptosis.nnnSIGNIFICANCEnWhile ER stress makes a necessary contribution to palmitate cytotoxicity, inhibition of CHOP alone is not sufficient to prevent palmitate-induced apoptosis. Our findings could advance the detailed understanding on the mechanism of high fatty acid (FFA)-induced apoptosis.

Amyloid oligomers in diabetic and nondiabetic human pancreas

The amyloid hypothesis of type 2 diabetes mellitus postulates that elevated levels of normally expressed monomeric proteins of human islet amyloid polypeptide (hIAPP) trigger oligomerization that independently causes fibril formation and disease progression. The aim of this study was to demonstrate the existence of amyloid oligomers in human pancreatic islets. Human pancreas tissues were obtained at autopsy of 8 nondiabetic control subjects (mean age = 75.8 +/- 11.7 years, 4 males), 8 type 2 diabetic cases without islet amyloid (mean age = 78.8 +/- 8.5 years, 4 males), and 8 type 2 diabetic patients with islet amyloid (mean age = 73.7 +/- 14.2 years, 4 males). Several markers for insulin, IAPP, amyloid fibrils (thioflavin T), and apoptosis (cleaved caspase-3) were used in combination with an oligomer-specific antibody. Two distinct forms of oligomers were found in pancreatic islets. Small spherical puncta were found in approximately 3% to 20% of the islet cells of nondiabetic subjects, and large curvilinear structures as extracellular oligomers were identified frequently in diabetic islets. Large oligomers were spatially localized adjacent to amyloid fibrils and were associated with apoptosis. This report demonstrates the presence of 2 morphologic classes of amyloid oligomers in human pancreatic islets. The observations warrant function studies to investigate the clinical implications of the amyloid oligomerization in the pathogenesis of type 2 diabetes.

White rice vinegar improves pancreatic beta-cell function and fatty liver in streptozotocin-induced diabetic rats

Vinegar is a traditional remedy for ailments including diabetes. This study was conducted to investigate the beneficial effects of vinegar in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic rats were orally administered with white rice vinegar (WRV, 2xa0ml/kg body weight per day, nxa0=xa06) or with an equal volume of drinking water (nxa0=xa06) for 1xa0month. Fasting and random blood glucose was measured from tail vein samples. Body weight, 24-h food and water intake were monitored 1xa0week and 1xa0month after STZ injection. Fasting serum insulin concentrations were assayed using ELISA. Pancreatic beta- and alpha-cell proportions were measured using immunofluorescence microscopy. Periodic acid Schiff staining was performed to access glycogen contents and histological changes in liver tissues. Compared with control animals, the WRV-treated rats had less weight loss, lower fasting and random blood glucose, higher fasting serum insulin and higher beta-cell proportion. The WRV treatment also improved fatty changes and glycogen storages in the liver of STZ rats. Oral intake of WRV improved fasting hyperglycemia and body weight loss through attenuating insulin deficiency, pancreatic beta-cell deficit, and hepatic glycogen depletion and fatty changes in STZ-induced diabetic rats.

Topographical associations between islet endocrine cells and duct epithelial cells in the adult human pancreas

Objectivesu2002 The pancreatic ducts, endocrine islets and exocrine acini are three functionally related components. From birth to adulthood, the islets and ducts are regarded as independent entities. The objective of this study is to investigate the topographical associations between the islet endocrine cells and duct epithelial cells in the adult human pancreas.