Mechanisms Regulating Insulin Response to Intragastric Glucose in Lean and Non-Diabetic Obese Subjects: A Randomized,Double-Blind,Parallel-Group Trial

Background/Objectives

The changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads.

Subjects/Methods

The study was conducted as a randomized, double-blind, parallel-group trial in a hospital research unit. A total of 12 normal weight (6 men and 6 women) and 12 non-diabetic obese (BMI > 30, 6 men and 6 women) participants took part in the study. Subjects received intragastric loads of 10 g, 25 g and 75 g glucose dissolved in 300 ml tap water.

Results

Main outcome measures were plasma GLP-1 and GIP, plasma glucagon, glucose, insulin, C-peptide and gastric emptying. The primary findings are: i) insulin resistance (P < 0.001) and hyperinsulinemia (P < 0.001); ii) decreased insulin disposal (P < 0.001); iii) trend for reduced GLP-1 responses at 75 g glucose; and iv) increased fasting glucagon levels (P < 0.001) in obese subjects.

Conclusions

It seems that, rather than changes in incretin secretion, fasting hyperglucagonemia and consequent hyperglycemia play a role in reduced disposal of insulin, contributing to hyperinsulinemia and insulin resistance.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01875575","term_id":"NCT01875575"}}NCT01875575     

Ecological Distribution and CQ11 Genetic Structure of Culex pipiens Complex (Diptera: Culicidae) in Italy

Mosquitoes in the Culex pipiens complex are considered to be involved in the transmission of a range of pathogens, including West Nile virus (WNV). Although its taxonomic status is still debated, the complex includes species, both globally distributed or with a more limited distribution, morphologically similar and characterised by different physiological and behavioural traits, which affect their ability as vectors. In many European countries, Cx. pipiens and its sibling species Culex torrentium occur in sympatry, exhibiting similar bionomic and morphological characters, but only Cx. pipiens appears to play a vector role in WNV transmission. This species consists of two biotypes, pipiens and molestus, which can interbreed when in sympatry, and their hybrids can act as WNV-bridge vectors, due to intermediate ecological features. Considering the yearly WNV outbreaks since 2008 and given the morphological difficulties in recognising species and biotypes, our aim was to molecularly identify and characterised Cx. pipiens and Cx. torrentium in Italy, using recently developed molecular assays. Culex torrentium was not detected; as in other European countries, the pipiens and molestus biotypes were widely found in sympatry with hybrids in most environments. The UPGMA cluster analysis applied to CQ11 genotypic frequencies mainly revealed two groups of Cx. pipiens populations that differed in ecological features. The high propensity of the molestus biotype to exist in hypogean environments, where the habitat’s physical characteristics hinder and preclude the gene flow, was shown. These results confirmed the CQ11 assay as a reliable diagnostic method, consistent with the ecological and physiological aspects of the populations analysed. Since the assessment of the actual role of three biotypes in the WNV circulation remains a crucial point to be elucidated, this extensive molecular screening of Cx. pipiens populations can provide new insights into the ecology of the species and may give useful indications to plan and implement WNV surveillance activities in Italy.     

Short term changes in pore water chemistry in river sediments during the early colonization by <Emphasis Type="Italic">Vallisneria spiralis</Emphasis>

Benthic consumers influence stream ecosystem structure and function, but these interactions depend on environmental context. We experimentally quantified the effects of central stoneroller minnows (Campostoma anomalum (Rafinesque) and Meek’s crayfish (Orconectes meeki meeki (Faxon)) on benthic communities using electric exclusion quadrats in Little Mulberry Creek before (June) and during (August) seasonal stream drying. Unglazed ceramic tiles were deployed in June and August to measure periphyton and invertebrate abundance, and leafpack decomposition and primary production were also measured in August. Relationships between stoneroller and crayfish density and the size of consumer effects were evaluated with multiple linear regression models. Average chlorophyll a abundance was greater on exposed than exclusion tiles in August, but not in June. Sediment dry mass, periphyton ash-free dry mass (AFDM), and chironomid densities on tiles did not differ among treatments in either period. Leaf packs decayed faster in exposed than exclusion treatments (k _exposed = 0.038 ± 0.013, k _exclusion = 0.007 ± 0.002), but consumer effects were stronger in some pools than others. Leafpack invertebrate biomass and abundance and tile primary productivity did not differ among treatments. Consumer effects on chlorophyll a were related to crayfish and stoneroller density, and effects on chironomid density were related to stoneroller density. These results contrast with a previous exclusion experiment in Little Mulberry Creek that demonstrated strong consumer effects. The influence of stream drying on consumer effects appears to have been reduced by strong spates, underscoring the importance of conducting multi-year studies to determine the magnitude of variability in ecological interactions.     

IFNL4 and IFNL3 Associated Polymorphisms Strongly Influence the Spontaneous IFN-Alpha Receptor-1 Expression in HCV-Infected Patients

Single-nucleotide polymorphism in IFNL3 gene (rs12979860) predicts spontaneous and therapy-induced HCV clearance. In a previous study from our group PBMC from patients with favourable rs12979860 genotype showed higher levels of IFNAR-1 mRNA. Recently, a dinucleotide polymorphism, ss469415590 (TT or ΔG), has been discovered in the region upstream IFNL3 gene, which is in high linkage disequilibrium with rs12979860. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designed IFNL4, encoding the interferon-lambda 4 protein (IFNL4). The aim of the present study was to extend the analysis of IFNAR-1 mRNA levels to the ss469415590 variants. Our results highlight that the difference of IFNAR-1 mRNA levels between favourable and unfavourable genotype combinations, at both rs12979860 and ss469415590 loci, is stronger than that observed for single polymorphisms at each locus. These findings suggest may represent the biological basis for the observed association between IFNL3 CC and IFNL4 TT/TT genotypes and favourable outcome of either natural HCV infection (clearance vs chronic evolution) or IFN-based therapy.     

Design of an harmonic radar for the tracking of the Asian yellow‐legged hornet

The yellow‐legged Asian hornet is an invasive species of wasps, indigenous to the Southeast Asia but recently spreading in Southern Europe. Because of its exponential diffusion and its serious threat to the local honeybee colonies (and to humans as well), restraint measures are currently under investigation. We developed and tested an harmonic radar capable of tracking the flying trajectory of these insects, once equipped with a small transponder, in their natural environment. Several hornets were captured close to a small cluster of honeybee hives, tagged with different transponders and then released in order to follow the flight toward their nest. On‐field testing proved an initial maximum detection range of about 125 m in a hilly and woody area. A number of detections were clearly recorded, and preferential directions of flight were identified. The system herein described is intended as a first low‐cost harmonic radar; it proved the capability to track the hornets while flying and it permitted to test the tagging techniques. Several upgrades of the system have been identified during this work and are extensively described in the last chapter. The designed system has three major advantages over conventional harmonic radars. First and most importantly, it adopts advanced processing techniques to suppress clutter and to improve target detection. Second, it allows radar operations in complex environments, generally hilly and rich in vegetation. Finally, it can continuously track tagged insects (24/7) and in any meteorological condition, providing an effective tool in order to locate the nests of the yellow‐legged Asian hornet.