Compatibility between the endoparasitoid Hyposoter didymator and the entomopathogenic fungus Metarhizium brunneum: A laboratory simulation for the simultaneous use to control Spodoptera littoralis

BACKGROUND The cotton leafworm, Spodoptera littoralis, is one of the most destructive pests in the Mediterranean basin, being predominantly controlled using synthetic chemical pesticides. Strain EAMa 01/58‐Su of the fungus Metarhizium brunneum and the parasitoid Hyposoter didymator are promising biological control agents for this pest. In this study, we assessed the compatibility between these two agents to control S. littoralis under joint attack scenarios. RESULTS Firstly, the direct and indirect effects of the fungus towards parasitoid adults were studied. The fungus significantly decreased life expectancy of the parasitoid (mortality=62.5%; mean lethal concentration=1.85×106 conidia ml‐1; average survival time=92.2h) when applied at high concentrations (108 conidia ml‐1), whereas it did not affect the reproductive potential of the parasitoid females during the three days after treatment. Secondly, the combinations between the two agents to control S. littoralis under different simultaneous use scenarios (inoculation of S. littoralis larvae with the fungus before being exposed to parasitoid females and vice versa) were investigated, with additive effect in all cases. A significant effect on fitness (preimaginal development time and reproductive potential) of the F1 parasitoid generation were detected. Moreover, parasitization significantly reduced the total haemocytes in S. littoralis haemolymph compared with the control, promoting fungal infection. Finally, parasitoids showed a significant preference for non‐inoculated S. littoralis larvae. CONCLUSIONS We demonstrated compatibility (additive effect) between fungus and parasitoid under different joint attack scenarios to control S. littoralis in laboratory conditions. However, this will be supported by our ongoing greenhouse and field studies

Lipopolysaccharides Impair Insulin Gene Expression in Isolated Islets of Langerhans via Toll-Like Receptor-4 and NF-κB Signalling

BACKGROUND:Type 2 diabetes is characterized by pancreatic β-cell dysfunction and is associated with low-grade inflammation. Recent observations suggest that the signalling cascade activated by lipopolysaccharides (LPS) binding to Toll-Like Receptor 4 (TLR4) exerts deleterious effects on pancreatic β-cell function; however, the molecular mechanisms of these effects are incompletely understood. In this study, we tested the hypothesis that LPS alters insulin gene expression via TLR4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in islets. METHODOLOGY/PRINCIPAL FINDINGS:A 24-h exposure of isolated human, rat and mouse islets of Langerhans to LPS dose-dependently reduced insulin gene expression. This was associated in mouse and rat islets with decreased mRNA expression of pancreas-duodenum homebox-1 (PDX-1) and mammalian homologue of avian MafA/l-Maf (MafA). Accordingly, LPS exposure also decreased glucose-induced insulin secretion. LPS repression of insulin, PDX-1 and MafA expression, as well as its inhibition of insulin secretion, were not observed in islets from TLR4-deficient mice. LPS inhibition of β-cell gene expression in rat islets was prevented by inhibition of the NF-κB pathway, but not the p38 mitogen-activated protein kinase (p38 MAPK) pathway. CONCLUSIONS/SIGNIFICANCE:Our findings demonstrate that LPS inhibit β-cell gene expression in a TLR4-dependent manner and via NF-κB signaling in pancreatic islets, suggesting a novel mechanism by which the gut microbiota might affect pancreatic β-cell function

The Role of IRE1α in the Degradation of Insulin mRNA in Pancreatic β-Cells

The endoplasmic reticulum (ER) is a cellular compartment for the biosynthesis and folding of newly synthesized secretory proteins such as insulin. Perturbations to ER homeostasis cause ER stress and subsequently activate cell signaling pathways, collectively known as the Unfolded Protein Response (UPR). IRE1α is a central component of the UPR. In pancreatic β-cells, IRE1α also functions in the regulation of insulin biosynthesis.Here we report that hyperactivation of IRE1α caused by chronic high glucose treatment or IRE1α overexpression leads to insulin mRNA degradation in pancreatic β-cells. Inhibition of IRE1α signaling using its dominant negative form prevents insulin mRNA degradation. Islets from mice heterozygous for IRE1α retain expression of more insulin mRNA after chronic high glucose treatment than do their wild-type littermates.These results reveal a role of IRE1α in insulin mRNA expression under ER stress conditions caused by chronic high glucose. The rapid degradation of insulin mRNA could provide immediate relief for the ER and free up the translocation machinery. Thus, this mechanism would preserve ER homeostasis and help ensure that the insulin already inside the ER can be properly folded and secreted. This adaptation may be crucial for the maintenance of β-cell homeostasis and may explain why the β-cells of type 2 diabetic patients with chronic hyperglycemia stop producing insulin in the absence of apoptosis. This mechanism may also be involved in suppression of the autoimmune type 1 diabetes by reducing the amount of misfolded insulin, which could be a source of “neo-autoantigens.

Palmitate-Induced β-Cell Dysfunction Is Associated with Excessive NO Production and Is Reversed by Thiazolidinedione-Mediated Inhibition of GPR40 Transduction Mechanisms

BACKGROUND: Type 2 diabetes often displays hyperlipidemia. We examined palmitate effects on pancreatic islet function in relation to FFA receptor GPR40, NO generation, insulin release, and the PPARgamma agonistic thiazolidinedione, rosiglitazone. PRINCIPAL FINDINGS: Rosiglitazone suppressed acute palmitate-stimulated GPR40-transduced PI hydrolysis in HEK293 cells and insulin release from MIN6c cells and mouse islets. Culturing islets 24 h with palmitate at 5 mmol/l glucose induced beta-cell iNOS expression as revealed by confocal microscopy and increased the activities of ncNOS and iNOS associated with suppression of glucose-stimulated insulin response. Rosiglitazone reversed these effects. The expression of iNOS after high-glucose culturing was unaffected by rosiglitazone. Downregulation of GPR40 by antisense treatment abrogated GPR40 expression and suppressed palmitate-induced iNOS activity and insulin release. CONCLUSION: We conclude that, in addition to mediating acute FFA-stimulated insulin release, GPR40 is an important regulator of iNOS expression and dysfunctional insulin release during long-term exposure to FFA. The adverse effects of palmitate were counteracted by rosiglitazone at GPR40, suggesting that thiazolidinediones are beneficial for beta-cell function in hyperlipidemic type 2 diabetes

BMI is an important driver of beta-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children.

OBJECTIVE: Body weight-related insulin resistance probably plays a role in progression to type 1 diabetes, but has an uncertain impact following diagnosis. In this study, we investigated whether BMI measured at diagnosis was an independent predictor of C-peptide decline 1-year post-diagnosis. DESIGN: Multicentre longitudinal study carried out at diagnosis and up to 1-year follow-up. METHODS: Data on C-peptide were collected from seven diabetes centres in Europe. Patients were grouped according to age at diagnosis (5 years 10 years 18 years, n=410). Linear regression was used to investigate whether BMI was an independent predictor of change in fasting C-peptide over 1 year. Models were additionally adjusted for baseline insulin dose and HbA1c. RESULTS: In individuals diagnosed between 0 and 5 years, 5 and 10 years and those diagnosed >18 years, we found no association between BMI and C-peptide decline. In patients aged 10-18 years, higher BMI at baseline was associated with a greater decline in fasting C-peptide over 1 year with a decrease (beta 95% CI; P value) of 0.025 (0.010, 0.041) nM/kg per m(2) higher baseline BMI (P=0.001). This association remained significant after adjusting for gender and differences in HbA1c and insulin dose (beta=0.026, 95% CI=0.0097, 0.042; P=0.002). CONCLUSIONS: These observations indicate that increased body weight and increased insulin demand are associated with more rapid disease progression after diagnosis of type 1 diabetes in an age group 10-18 years. This should be considered in studies of beta-cell function in type 1 diabetes