Article

Impaired glucose tolerance in mice lacking cellular prion protein.

Chronic Disease Program, Institute for Clinical Diabetology, German Diabetes Centre, Du¨sseldorf, Germany.
Pancreas (Impact Factor: 2.95). 03/2011; 40(2):229-32. DOI: 10.1097/MPA.0b013e3181f7e547
Source: PubMed

ABSTRACT We previously demonstrated that the expression of cellular prion protein (PrPC) in islet [beta]-cells is suppressed in hyperglycemic rats suggesting a major role for PrPC in blood glucose regulation. To further characterize the function of PrPC in glucose homeostasis, we studied glucoregulation in PrPC knockout (PrPC KO) mice.
Glucose tolerance, insulin secretion, and insulin sensitivity were analyzed to assess glucoregulation in Zrch I PrPC KO and the C57BL/6 (control) mice. Immunohistochemistry and morphometry were used to measure [beta]-cell mass.
Male PrPC KO mice had significantly increased blood glucose concentration 60, 120, and 180 minutes after intraperitoneal injection of glucose compared with C57BL/6 mice. Female PrPC KO mice showed a less pronounced phenotype of glucose intolerance. Evaluation of [beta]-cell mass, insulin and proinsulin deficiency, and insulin resistance in male mice revealed essentially no difference between PrPC KO and control mice. The only exception was an increase in serum insulin concentration in male PrPC KO mice 5 minutes after glucose injection.
This report is the first to show that PrPC in [beta]-cells is involved in glucoregulation. A further understanding of the role of PrPC in regulating [beta]-cell function will provide valuable insight into the mechanisms of blood glucose regulation.

0 Bookmarks
 · 
123 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Deletion of cellular isoform of prion protein (PrP C) increases neuronal predisposition to damage by modulating apoptosis and the negative consequences of oxidative stress. In vivo studies have demonstrated that PrP C -deficient mice are more prone to seizure, depression, and induction of epilepsy and experience extensive cerebral damage following ischemic challenge or viral infection. In addition, adenovirus-mediated overexpression of PrP C reduces brain damage in rat models of cerebral ischemia. In experimental autoimmune encephalomyelitis, PrP C -deficient mice reportedly have a more aggressive disease onset and less clinical improvement during the chronic phase than wild-type mice mice. In mice given oral dextran sulfate, PrP C has a potential protective role against inflammatory bowel disease. PrP C -deficient mice demonstrate significantly greater increases in blood glucose concentrations after intraperitoneal injection of glucose than wild-type mice. Further in vivo challenges to PrP gene-deficient models and conditional knockout models with siRNA and in vivo administration of PrP-ligating agents may assist in refining knowledge of the lymphoid function of PrP C and predicting the effects of anti-PrP treatment on the immune system. Together, these findings indicate that PrP C may have multiple neuroprotective and anti-inflammatory roles, which explains why this protein is so widely expressed.
    Microbiology and Immunology 07/2014; 58(7):361-374. · 1.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prion diseases are a group of neurodegenerative diseases that are fatal. The study of these unique diseases in China is hampered by a lack of resources. Amongst the most important resources for biological study are monoclonal antibodies. Here, we characterize a panel of monoclonal antibodies specific for cellular prion protein by enzyme-linked immunosorbent assay (ELISA), immunofluorescent staining, flow cytometry, and western blotting. We identify several antibodies that can be used for specific applications and we demonstrate that there is no prion protein expression in human pancreatic ductal epithelial cells (HPDC).
    Virologica Sinica 08/2014; 29(4):228-236.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity has become one of the largest public health challenges worldwide. Recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. In the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (BSE)-infected female cynomolgus monkeys (Macaca fascicularis). The original study design aimed to determine minimal infectious doses after oral or intracerebral (i.c.) infection of macaques to assess the risk for humans. High-dose exposures resulted in 100% attack rates and a median incubation time of 4.7 years as described previously. Retrospective analyses of clinical data from high-dosed macaques revealed that foodborne BSE transmission caused rapid weight gain within 1.5 years post infection (β = 0.915; P<0.0001) which was not seen in age- and sex-matched control animals or i.c. infected animals. The rapid-onset obesity was not associated with impaired pancreatic islet function or glucose metabolism. In the early preclinical phase of oral transmission associated with body weight gain, prion accumulation was confined to the gastrointestinal tract. Intriguingly, immunohistochemical findings suggest that foodborne BSE transmission has a pathophysiological impact on gut endocrine cells which may explain rapid weight gain. To our knowledge, this is the first experimental model which clearly demonstrates that foodborne pathogens can induce obesity.
    PLoS ONE 01/2014; 9(8):e104343. · 3.53 Impact Factor