Insulin sensitivity : modulation by neuropeptides and hormones

Nowadays, obesity has reached epidemic proportions globally. It can lead to several chronic diseases, including insulin resistance/type 2 diabetes mellitus. Feeding behaviour is regulated in the hypothalamus of the brain by two opposing pathways: NPY/AgRP neurons vs. POMC/CART neurons. In addition, there are numerous peripheral signals, deriving from stomach, gut, pancreas and adipose tissue, that act on the hypothalamus and thereby contribute to the regulation of food intake. The aim of the studies we have performed, was to investigate the effects of some of these neuropeptides and peripheral signals that affect these neuropeptides, on insulin action. Our experiments showed, that NPY can cause insulin resistance, specifically in the liver. The POMC pathway can improve insulin-mediated glucose disposal and does not affect hepatic insulin sensitivity. Therefore, both pathways are not completely opposing each other’s effects, but seem to have a different tissue-specific effect. Experiments with gut hormones like PYY and ghrelin showed that these hormones affect insulin sensitivity as well. Also leptin, and specifically leptin signalling in the brain, was found to be important for insulin sensitivity. In conclusion, this work showed that neuropeptides/hormones that are involved in the regulation of food intake also affect insulin sensitivity.​​​​​​​LEI Universiteit LeidenThe printing of this thesis was financially supported by: TNO-Quality of Life, the Gaubius Laboratory Dutch Diabetes Research Foundation Van Leersumfonds KNAW Eli Lilly Nederland Novo Nordisk Farma B.V. Hope Farms / abdiets, W oerdenDe pathogenese, kliniek en behandeling van arterieel en veneus vaatlijde

Change in the distribution of a member of the strand line community: the seaweed fly (Diptera: Coelopidae)

1. Coastal organisms are predicted to be particularly susceptible to the impact of global warming. In this study the distribution and relative abundance of two coastal invertebrates, Coelopa frigida (Fabricius) and C. pilipes are investigated. 2. Coelopa pilipes has a more southerly distribution than C. frigida , and prefers a warmer climate. Coelopa pilipes is less resistant to sub-zero temperatures than C. frigida and its northerly distribution is probably limited by cold winter days. 3. The most recent distribution map of C. frigida and C. pilipes in northern Europe was published a decade ago and showed the northerly extent of the distribution of C. pilipes reaching the north coast of mainland Scotland but its complete absence from the Western and Northern Isles. 4. C. pilipes has now spread throughout the Western Isles and the Orkney Islands but is still absent from Shetland. There has also been an increase in the relative frequency of C. pilipes at sites harbouring coelopids on the British mainland. A similar pattern of distribution change along the west coast of Sweden is reported. 5. It is proposed that these changes have occurred primarily as a result of global warming and in particular due to the recent increase in winter temperatures. A number of other indirect effects may have also contributed to these changes, including a probable change in macroalgae distribution. The implications of these changes for the wrack bed ecosystem and at higher trophic levels are considered

Prognostic Implications of Lateral Lymph Nodes in Rectal Cancer:A Population-Based Cross-sectional Study with Standardized Radiological Evaluation after Dedicated Training

BACKGROUND: There is an ongoing discussion regarding the prognostic implications of the presence, short-axis diameter, and location of lateral lymph nodes. OBJECTIVE: To analyze lateral lymph node characteristics, the role of downsizing on restaging MRI, and associated local recurrence rates for patients with cT3-4 rectal cancer after MRI re-review and training. DESIGN: Retrospective population-based cross-sectional study. SETTINGS: This collaborative project was led by local investigators from surgery and radiology departments in 60 Dutch hospitals. PATIENTS: A total of 3057 patients underwent rectal cancer surgery in 2016: 1109 had a cT3-4 tumor located ≤8 cm from the anorectal junction, of whom 891 received neoadjuvant therapy. MAIN OUTCOME MEASURES: Local recurrence and (ipsi) lateral local recurrence rates. RESULTS: Re-review identified 314 patients (35%) with visible lateral lymph nodes. Of these, 30 patients had either only long-stretched obturator (n = 13) or external iliac (n = 17) nodes, and both did not lead to any lateral local recurrences. The presence of internal iliac/obturator lateral lymph nodes (n = 284) resulted in 4-year local recurrence and lateral local recurrence rates of 16.4% and 8.8%, respectively. Enlarged (≥7 mm) lateral lymph nodes (n = 122) resulted in higher 4-year local recurrence (20.8%, 13.1%, 0%; p &lt;.001) and lateral local recurrence (14.7%, 4.4%, 0%; p &lt; 0.001) rates compared to smaller and no lateral lymph nodes, respectively. Visible lateral lymph nodes (HR 1.8 [1.1-2.8]) and enlarged lateral lymph nodes (HR 1.9 [1.1-3.5]) were independently associated with local recurrence in multivariable analysis. Enlarged lateral lymph nodes with malignant features had higher 4-year lateral local recurrence rates of 17.0%. Downsizing had no impact on lateral local recurrence rates. Enlarged lateral lymph nodes were found to be associated with higher univariate 4-year distant metastasis rates (36.4% vs 24.4%; p = 0.021), but this was not significant in multivariable analyses (HR 1.3 [0.9-1.]) and did not worsen overall survival. LIMITATIONS: This study was limited by the retrospective design and total number of patients with lateral lymph nodes. CONCLUSIONS: The risk of lateral local recurrence due to (enlarged) lateral lymph nodes was confirmed, but without the prognostic impact of downsizing after neoadjuvant therapy. These results point toward the incorporation of primary lateral lymph node size into treatment planning. See Video Abstract.</p

The CCR2 Inhibitor Propagermanium Attenuates Diet-Induced Insulin Resistance, Adipose Tissue Inflammation and Non-Alcoholic Steatohepatitis

Vascular Surger

Chemical food safety hazards of insects reared for food and feed

Insects are a promising future source of sustainable proteins within a circular economy. Proving the safety of insects for food and feed is necessary prior to supplying them to the market. This literature review provides a state-of-the-art overview of the chemical food safety hazards for insects reared for food and feed, focusing mainly on transfer of contaminants from the substrate. Contaminants covered are: heavy metals, dioxins and polychlorinated biphenyls, polyaromatic hydrocarbons, pesticides, veterinary drugs, mycotoxins, and plant toxins. The twelve insect species reported as having the largest potential as feed and food in the EU are included. Transfer and bioaccumulation of contaminants depend on the chemical, insect species, life stage, and source of contaminant (spiked vs natural), as well as the particular substrate and rearing conditions. The heavy metals lead, arsenic, mercury, and cadmium can accumulate, whereas mycotoxins and polycyclic aromatic hydrocarbons (PAHs) seem not to accumulate. Mycotoxins and veterinary drugs could be degraded by insects; their metabolic routes need to be further investigated. Data are generally limited, but in particular for PAHs, plant toxins, and dioxins and dioxin-like polychlorinated biphenyls. Further research on chemical safety of different edible insects is therefore warranted

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