Background:  Cinnamomum cassia (Family: Lauraceae) is an Ayurvedic medicinal plant used traditionally for the treatment of a number of diseases, including diabetes. The hypoglycemic effect of this plant has been established in vivo. However, the effects of cinnamic acid, isolated from C. cassia, on the insulin signaling cascade in an in vitro model have not been elucidated. Hence, the aim of the present study was to evaluate the anti‐diabetic effect of cinnamic acid on glucose transport by L6 myotubes. Methods:  The mechanism of action of cinnamic acid was determined using specific targets in the insulin signaling pathway, including protein tyrosine phosphatase (PTP) 1B, phosphatidylinositol 3‐kinase (PI3‐K) and the glucose transporter GLUT4. After differentiation of myoblast to myotubes, the cells were serum deprived for 5 h and then treated with 1 ng/mL cinnamic acid and 50 μmol/L rosiglitazone for 18 h and 100 nmol/L insulin for 20 min for gene expression studies. Results:  Expression of GLUT4 mRNA was increased following treatment of L6 myotubes with 1 ng/mL cinnamic acid. Furthermore, cinnamic acid inhibited PTP1B activity (by 96.5%), but had no significant effect on PI3‐K activity. Conclusion:  On the basis of the results of the present study, we postulate that cinnamic acid isolated from the hydro‐alcoholic extract of Cinnamomum cassia activates glucose transport by a PI3‐K‐independent pathway. However, the detailed mechanism of action requires further analysis.

Early development of the rumen, rumination, and fermentation is highly important in dairy calves. Yet, common rearing practices with feeding of concentraterich starters may jeopardize them because of lacking physically effective fiber (peNDF). The main objective of this study was to establish the influence of the composition of the calf starter feed (only forage with 2 different qualities or concentrate-rich starter diet) on chewing behavior, rumen development, rumen and hindgut fermentation, and selected systemic health and stress variables of dairy calves. The experiment was carried out with 40 newborn Holstein-Friesian calves, randomly assigned to 4 different solid feed treatments: MQH = 100% medium-quality hay (9.4 MJ metabolizable energy, 149 g of crude protein, and 522 g of neutral detergent fiber/kg of dry matter); HQH = 100% highquality hay (11.2 MJ of metabolizable energy, 210 g of crude protein, 455 g of neutral detergent fiber/kg of dry matter); MQH+C = 30% MQH + 70% starter concentrate; HQH+C = 30% HQH + 70% starter concentrate). All calves were up to 14 wk in the trial and received acidified whole milk ad libitum in the first 4 wk of life, thereafter in reduced quantity until weaning on 12 wk of age. Water and the solid feed treatments were available ad libitum throughout the trial. Chewing activity was measured in wk 4, 6, 10, and 12 using RumiWatch halters. Until wk 3, rumen fluid, feces and blood were sampled weekly, thereafter every 2 wk. Rumen mucosal thickness (RMT) was measured on the same days with rumen fluid samples. Data showed that calves fed the HQH diet consumed more peNDF and this was associated with longer rumination time (591 min/d) and more ruminating boli (709 boli/d) than calves fed concentrate-rich diets (MQH+C: 430 min/d, 518 boli/d; HQH+C: 430 min/d, 541 boli/d), whereas the MQH group was intermediate (539 min/d, 644 boli/d). Ruminal and fecal pH were higher in calves fed only hay (especially MQH) compared with calves with concentrate supplementation. In both hay-fed groups, ruminal and fecal short-chain fatty acids were shifted toward acetate, whereas only the HQH diet increased the butyrate proportion in the ruminal short-chain fatty acids profile. Ruminal ammonia concentration was at a high level only in the first 3 wk and decreased thereafter. Feeding HQH tended to increase ruminal ammonia, likely because of its high crude protein content and ruminal degradability as well as lower assimilation from rumen microbes. The RMT similarly, though nonlinearly, increased in all groups over the course of the experiment. When using RMT as an indicator of rumen development in dairy calves in the practice, our data suggest an RMT of 1.7 mm and >2 mm at wk 5 and 10 of life, respectively. Feeding did not affect the blood levels of aspartate aminotransferase, gamma glutamyl transferase, glutamate dehydrogenase, and cortisol. In conclusion, feeding high-quality hay, instead of concentrate-rich starter feeds, resulted in improved rumination and ruminal fermentation profile, without affecting...

Despite their anti-inflammatory properties, role in barrier function, absorption and microbial balance in the gut, knowledge on maturational and dietary effects on intestinal short-chain fatty acids (SCFA) in neonatal piglets is scarce. Moreover, little information exists whether SCFA and lactic acid (LA) modulates gut motility at this age. The present study aimed 1) to investigate the maturational changes in the SCFA profile with and without creep feeding of piglets in the first 3 weeks of life; and 2) to examine the effects of SCFA and LA on muscle contractibility in jejunal tissue from neonatal piglets ex vivo. SCFA concentrations were measured in fecal samples of 52 piglets from 10 litters collected on days 2, 6, 13, and 20 of life using gas chromatography. Half of the litters were fed a commercial creep feed from day 10 of life. The organ bath system was used to test the effect of SCFA (acetate, propionate, butyrate, isobutyrate, valerate, isovalerate and caproate) as well as of LA and the combination of LA and SCFA on muscle contractibility in piglet’s jejunum. Average daily gain of piglets was similar between groups before and after introduction of creep feed. SCFA were detectable in feces in relevant concentrations from day 2 of life and increased on day 6 in males by 3.0-fold and on day 13 in females by 1.6-fold but decreased again on day 20 in both sexes compared to day 2 (P < 0.05). Creep feeding reduced fecal SCFA by 0.6-fold on day 13 without largely modifying molar proportions, whereas it increased fecal SCFA by 0.8-fold on day 20 of life compared to the sow-reared only piglets (P < 0.05). Applying SCFA ex vivo increased the muscle contraction of the jejunum by 30% (P < 0.05). Likewise, addition of LA and the combination of LA and SCFA increased the jejunal muscle contractibility by 34.9 and 32.2%, respectively, compared to the muscle tension pre-addition (P < 0.05). In conclusion, the present results for fecal SCFA in first days of life suggest high bacterial activity on milk components and emphasize the importance of SCFA for intestinal development and function. After a lag phase, creep feeding promotes fermentation in the distal colon, which may be beneficial for the gut homeostasis. Results further demonstrate the stimulating effect of SCFA and LA for jejunal motility, suggesting a role for mixing of digesta (segmentation) and digestion and absorption of nutrients as well as passage in the jejunum of neonatal piglets.

Dietary and microbially derived fatty acids (FA) play important roles in gut mucosal inflammatory signaling, barrier function and oxidative stress response. Nevertheless, little information is available about gastrointestinal FA profiles and receptor distribution in pigs, especially for long-chain FA (LCFA). Therefore, the present pilot study aimed to 1) investigate the gastrointestinal FA profiles; 2) link the luminal FA profiles to the mucosal expression of genes related to FA sensing and signaling; and 3) assess potential dietary effects on gut and systemic lipid metabolism in pigs. Gut, liver and serum samples were obtained from barrows (13.1 ± 2.3 kg) fed diets containing either phytase (500 phytase units/kg diet) or cereals treated with 2.5% lactic acid (LA) (n = 8/diet) for 18 days. Results showed gut regional and diet-related differences in luminal FA profiles and mucosal receptor expression, whereas diet little affected hepatic expression levels and serum lipids. Short-chain fatty acids (SCFA) increased from stomach, jejunum and ileum to the cecum (P < 0.05), whereas LCFA were higher in stomach, cecum and colon than in jejunum and ileum (P < 0.05). LA-treated cereals enhanced cecal acetate and butyrate, whereas phytase and LA treated cereals decreased the LCFA by 35.9 and 14.4%, respectively (P < 0.05). Gut regional differences suggested stronger signaling via FFAR1 expression in the ileum, and via FFAR2, FFAR4 and HCAR1 expression in cecum and colon (P < 0.05). Expression of AMPK, FASN, PPARG, SREBP1 and SREBP2 was higher in the cecum and colon compared to the small intestine (P < 0.05), with stronger sensing via FASN and SREBP2. Phytase decreased expression of FFAR2 and FFAR4, whereas it increased that of FFAR3 and MCT1 in the cecum (P < 0.05). LA-treated cereals raised cecal expression of FFAR3 and HCAR1 (P < 0.05). Pearson’s correlations (|r| > 0.35; P < 0.05) supported that FA receptor- and nuclear transcription factor-dependent pathways were involved in the mucosal regulation of gut incretin expression but differed across gut regions. In conclusion, results support regional differences in SCFA, lactate and LCFA sensing and absorption capacities in the small and large intestines of pigs. Effects of phytase and the LA-treated cereals on intestinal FA levels and signaling can be explained by differences in nutrient flows (e.g. phosphorus and carbohydrate fractions). This overview provides a solid basis for future intestinal FA sensing in pigs.

Aim:The mechanism of action of Annona squamosa hexane extract in mediating antihyperglycemic and antitriglyceridimic effect were investigated in this study.Materials and Methods:The effects of extract on glucose uptake, insulin receptor-β (IR-β), insulin receptor substrate-1 (IRS-1) phosphorylation and glucose transporter type 4 (GLUT4) and phosphoinositide 3-kinase (PI3 kinase) mRNA expression were studied in L6 myotubes. The in vitro mechanism of action was tested in protein-tyrosine phosphatase 1B (PTP1B), G-protein-coupled receptor 40 (GPR40), silent mating type information regulation 2 homolog 1 (SIRT1) and dipeptidyl peptidase-IV (DPP-IV) assays. The in vivo efficacy was characterized in ob/ob mice after an oral administration of the extract for 21 days.Results:The effect of extract promoted glucose uptake, IR-β and IRS-1 phosphorylation and GLUT4 and PI3 kinase mRNA upregulation in L6 myotubes. The extract inhibited PTP1B with an IC50 17.4 μg/ml and did not modulate GPR40, SIRT1 or DPP-IV activities. An oral administration of extract in ob/ob mice for 21 days improved random blood glucose, triglyceride and oral glucose tolerance. Further, the extract did not result in body weight gain before and after treatment (29.3 vs. 33.6 g) compared to rosiglitazone where significant body weight gain was observed (28.4 vs. 44.5 g; *P<0.05 after treatment compared to before treatment).Conclusion:The results suggest that Annona squamosa hexane extract exerts its action by modulating insulin signaling through inhibition of PTP1B.