Loss of β-cell mass and function is a fundamental feature of pathogenesis for type 1 and type 2 diabetes. Increasing evidence indicates that apoptosis is one of the main mechanisms of β-cell death in both types. Ethanolic extracts of Pluchea indica leaf (PILE) have been reported to possess blood glucose lowering actions in vivo . Nevertheless, further study is required to determine the underlying mechanisms. In this report, we have investigated the preventive effects of PILE on multiple low doses of streptozotocin (MLDS)-induced β-cell apoptosis. Mice were pre-treated with PILE at 50 mg/kg (PILE 50) or 100 mg/kg (PILE 100) for 2 weeks before streptozotocin (STZ) stimulation, and the treatment continued for 4 or 8 weeks. Results revealed that PILE 100 mice exhibited improved blood biochemistry, maintained a higher body weight, had decreased hyperglycemia, and restored islet architectures compared to non-treated STZ mice. Significantly, PILE 100 decreased levels of inflammatory response markers interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interlukin1-β (IL-1β), concomitant with the inhibition of caspase-3, caspase-8, capsepase-9, phosphorylation of signal transducer and activator of transcription 1 (pSTAT1), nuclear factor-κBp65 (NF-κBp65), and inducible nitric oxide synthase (iNOS). Additionally, survival and proliferative ability of β-cells was mediated by up-regulated Bcl-2 and Ki67, respectively. These results provide strong evidence that pretreatment with PILE 100 effectively attenuated STZ-induced diabetes-related symptoms and these effects could be associated with the inhibition of cytokine-induced β-cell apoptosis.

Mutations of Wnt/β-catenin signaling pathway play essential roles in development and cancer. Although β-catenin and adenomatous polyposis coli (APC) gene mutations are well established and are known to drive tumorigenesis, discoveries of mutations in other components of the pathway lagged which hinders the understanding of cancer mechanisms. Here we report that δ-catenin (gene designation: CTNND2), a primarily neural member of the β-catenin superfamily which promotes canonical Wnt/β-catenin/LEF-1-mediated transcription, displays exonic mutations in human prostate cancer and promotes cancer cell survival adaptation and metabolic reprogramming. When overexpressed in cells derived from prostate tumor xenografts, δ-catenin gene invariably gave rise to mutations leading to sequence disruptions predicting functional alterations. Ectopic δ-catenin gene integrating into host chromosomes is locus non-selective. δ-Catenin mutations promote tumor development in mouse prostate with probasin promoter (ARR2PB)-driven, prostate-specific expression of myc oncogene, while mutant cells empower survival advantage upon overgrowth and glucose deprivation. Reprogramming energy utilization accompanies the down-regulation of glucose transporter-1 (Glut-1) and Poly (ADP-ribose) polymerase (PARP) cleavage while preserving tumor type 2 pyruvate kinase (PKM2) expression. δ-Catenin mutations increased β-catenin translocation to the nucleus and HIF-1α expression. Therefore, introducing δ-catenin mutations is an important milestone in prostate cancer metabolic adaptation by modulating β-catenin and HIF-1α signaling under glucose shortage to amplify its tumor promoting potential.

Abnormalities in insulin hormone levels leads to a hyperglycemic condition of diabetic mellitus. Hyperglycemia seriously induces organ and system destructions. The excessive accumulation of collagen fiber deposits occurs in inflammatory and reorganization processes of chronic liver diseases in type I insulin-dependent diabetes. Regarding the research objective, glabridin (GLB), an active compound of licorice, was used as a daily supplement (40 mg/kg) in order to decrease hepatocyte destruction and collagen deposition in liver tissue of diabetic animals induced by streptozotocin. A total of 40 were randomly allocated to five groups (each, n=10), control, control treated with GLB (GLB), diabetic rats (DM) injected with single dose of streptozotocin (60 mg/kg) to induce a diabetic condition, diabetic rats receiving GLB (DM+GLB; 40 mg/kg) and diabetic rats treated with glibenclamide (DM+GL; 4 mg/kg). Characteristic histopathological changes in liver cells and tissues of rats were determined by Masson's trichrome staining and transmission electron microscopy (TEM). Western blotting was used to detect the expression of the key markers, collagen type I and fibronectin proteins. The histological investigation of liver tissue of the DM group revealed that the collagen fiber deposition was increased in the periportal, pericentral and perisinusoidal spaces compared with controls. Hepatocytes appeared as small and fragmented cells in TEM examination. Collagenization of the perisinusoidal space was recently demonstrated to represent a new aspect of the microvascular abnormalities and liver fibrosis. Healthy hepatocytes with round nucleus were observed following supplementation of glabridin. In addition, collagen fiber deposition was reduced in the area adjacent to the perisinusoidal space. The expression of collagen type I and fibronectin decreased strongly following glabridin supplementation in DM+GLB rats compared with DM rats, indicating that the hepatic tissue reorganization regained its normal morphology. These findings suggest that it may be beneficial to examine the role of glabridin as a therapeutic agent in diabetes treatment in future research.

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