Temporal Patterns of Glucagon and Its Relationships with Glucose and Insulin following Ingestion of Different Classes of Macronutrients

Background: glucagon secretion and inhibition should be mainly determined by glucose and insulin levels, but the relative relevance of each factor is not clarified, especially following ingestion of different macronutrients. We aimed to investigate the associations between plasma glucagon, glucose, and insulin after ingestion of single macronutrients or mixed-meal. Methods: thirty-six participants underwent four metabolic tests, based on administration of glucose, protein, fat, or mixed-meal. Glucagon, glucose, insulin, and C-peptide were measured at fasting and for 300 min following food ingestion. We analyzed relationships between time samples of glucagon, glucose, and insulin in each individual, as well as between suprabasal area-under-the-curve of the same variables (ΔAUCGLUCA, ΔAUCGLU, ΔAUCINS) over the whole participants’ cohort. Results: in individuals, time samples of glucagon and glucose were related in only 26 cases (18 direct, 8 inverse relationships), whereas relationship with insulin was more frequent (60 and 5, p < 0.0001). The frequency of significant relationships was different among tests, especially for direct relationships (p ≤ 0.006). In the whole cohort, ΔAUCGLUCA was weakly related to ΔAUCGLU (p ≤ 0.02), but not to ΔAUCINS, though basal insulin secretion emerged as possible covariate. Conclusions: glucose and insulin are not general and exclusive determinants of glucagon secretion/inhibition after mixed-meal or macronutrients ingestion.

Reversing chemorefraction in colorectal cancer cells by controlling mucin secretion

ABSTRACT15% of colorectal cancers (CRC) cells exhibit a mucin hypersecretory phenotype, which is suggested to provide resistance to immune surveillance and chemotherapy. We now formally show that colorectal cancer cells build a barrier to chemotherapeutics by increasing mucins’ secretion. We show that low levels of KChIP3, a negative regulator of mucin secretion (Cantero-Recasens et al., 2018), is a risk factor for CRC patients’ relapse in subset of untreated tumours. Our results also reveal that cells depleted of KChIP3 are four times more resistant (measured as cell viability and DNA damage) to chemotherapeutics 5-Fluorouracil plus Irinotecan (5-FU+iri.) compared to control cells, whereas KChIP3 overexpressing cells are 10 times more sensitive to killing by chemotherapeutics. Similar increase in tumour cell death is observed upon chemical inhibition of mucin secretion by the sodium/calcium exchanger (NCX) blockers (Mitrovic et al., 2013). Finally, sensitivity of CRC patient-derived organoids to 5-FU+iri increases 40-fold upon mucin secretion inhibition. Reducing mucin secretion thus provides a means to control chemoresistance of mucinous colorectal cancer cells and other mucinous tumours.

The depletion mechanism can actuate bacterial aggregation by self-produced exopolysaccharides and determine species distribution and composition in bacterial aggregates

Bacteria causing chronic infections are often found in cell aggregates suspended in polymer secretions, and aggregation may be a factor in infection persistence. One aggregation mechanism, called depletion aggregation, is driven by physical forces between bacteria and polymers. Here we investigated whether the depletion mechanism can actuate the aggregating effects of P. aeruginosa exopolysaccharides for suspended (i.e. not surface attached) bacteria, and how depletion affects bacterial inter-species interactions. We found cells overexpressing the exopolysaccharides Pel and Psl, but not alginate remained aggregated after depletion-mediating conditions were reversed. In co-culture, d epletion aggregation had contrasting effects on P. aeruginosa’s interactions with coccus- and rod-shaped bacteria. Depletion caused S. aureus (cocci) and P. aeruginosa (rods) to segregate from each other, S. aureus to resist secreted P. aeruginosa antimicrobial factors, and the species to co-exist. In contrast , depletion aggregation caused P. aeruginosa and Burkholderia sp. to intermix, enhancing type VI secretion inhibition of Burkholderia by P. aeruginosa , leading to P. aeruginosa dominance . These results show that in addition to being a primary cause of aggregation in polymer-rich suspensions, physical forces inherent to the depletion mechanism can actuate the aggregating effects of self-produced exopolysaccharides and determine species distribution and composition of bacterial communities.

Pengaruh Ekstrak Anggur Laut terhadap pH Lambung dan duodenum pada Rattus norvegicus Jantan yang Diinduksi Indometasin

Indomethacin is a nonsteroidal anti-inflammatory drugs (NSAIDs) that act to inhibit COX-1. The inhibition of COX-1 leads to inhibition of prostaglandin production. Prostaglandin is a regulator of gastric acid buffer secretion. Inhibition of prostaglandin decrease gastric and duodenum pH and damage the gastric and duodenum. Sea grapes (Caulerpa racemose var. cylindracea) are marcoalgae that contain flavonoids as antioxidants and anti-inflammatory. The aim of this study was to determine the effect of sea grapes on gastric and duodenum pH in rattus norvegicus induced by indomethacin. 32 male Rattus norvegicus were divided into 4 groups. Group K (-) without treatment. Group K (+) was induced by 30 mg/Kg BW indomethacin for 7 days. Group P1 was induced by 30mg/Kg BW indomethacin for 7 days followed by administration of 1g/100g BW sea grape extract for 14 days. Group P2 was induced by 30mg/Kg BW indomethacin for 7 days followed by administration of 2g/100g BW sea grape extract for 14 days. On the 29th day, rats were terminated, gastric and duodenal were isolated then the fluid pH was measured. One-way Anova test obtained p = 0,023. Post hoc test pH Gaster significantly different between group K (-) and K (+) (p= 0,005) and between group K (-) with P2 (p= 0,020). While in group K (+) with P1 and P2 there was no significant difference in pH. Post hoc test of pH duodenum showed no differences in all group. The administration of sea grape extract did not show a differences of the gastric and duodenal pH significantly between rats induced by indomethacin.