scholarly journals Baselines representing blood glucose clearance improve in vitro prediction of the glycaemic impact of customarily consumed food quantities

2009 ◽  
Vol 103 (2) ◽  
pp. 295-305 ◽  
Author(s):  
John A. Monro ◽  
Suman Mishra ◽  
Bernard Venn
Keyword(s):  
Blood Glucose ◽  
Glucose Disposal ◽  
Glucose Response ◽  
Food Quantity ◽  
Glucose Clearance ◽  
The Difference ◽  
Dose Dependent

Glycaemic responses to foods reflect the balance between glucose loading into, and its clearance from, the blood. Current in vitro methods for glycaemic analysis do not take into account the key role of glucose disposal. The present study aimed to develop a food intake-sensitive method for measuring the glycaemic impact of food quantities usually consumed, as the difference between release of glucose equivalents (GGE) from food during in vitro digestion and a corresponding estimate of clearance of them from the blood. Five foods – white bread, fruit bread, muesli bar, mashed potato and chickpeas – were consumed on three occasions by twenty volunteers to provide blood glucose response (BGR) curves. GGE release during in vitro digestion of the foods was also plotted. Glucose disposal rates estimated from downward slopes of the BGR curves allowed GGE dose-dependent cumulative glucose disposal to be calculated. By subtracting cumulative glucose disposal from cumulative in vitro GGE release, accuracy in predicting the in vivo glycaemic effect from in vitro GGE values was greatly improved. GGEin vivo = 0·99GGEin vitro+0·75 (R2 0·88). Furthermore, the difference between the curves of cumulative GGE release and disposal closely mimicked in vivo incremental BGR curves. We conclude that valid measurement of the glycaemic impact of foods may be obtained in vitro, and expressed as grams of glucose equivalents per food quantity, by taking account not only of GGE release from food during in vitro digestion, but also of blood glucose clearance in response to the food quantity.

scholarly journals Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 325 ◽  
Author(s):  
Xiaojuan Li ◽  
Yunping Tang ◽  
Fangmiao Yu ◽  
Yu Sun ◽  
Fangfang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Nude Mouse Model ◽  
Dose Dependent

We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future.

Impairment of glucose disposal by infusion of triglycerides in humans: role of glycemia

1989 ◽  
Vol 256 (6) ◽  
pp. E747-E752 ◽  
Author(s):  
C. P. Felley ◽  
E. M. Felley ◽  
G. D. van Melle ◽  
P. Frascarolo ◽  
E. Jequier ◽  
...  
Keyword(s):  
Glucose Oxidation ◽  
Plasma Free Fatty Acid ◽  
Regulatory Mechanisms ◽  
Glucose Disposal ◽  
Glucose Storage ◽  
Interaction Term ◽  
The Difference ◽  
Total Glucose

The present study was designed to assess the role of hyperglycemia (150 mg/dl) vs. euglycemia (90 mg/dl) on glucose metabolism in vivo during the infusion of a triglyceride emulsion (Intralipid). Seven young healthy volunteers were studied on four occasions using the hyperinsulinemic clamp technique, twice during euglycemia and twice during hyperglycemia, without or with Intralipid. Glucose oxidation (O) was calculated from continuous respiratory exchange measurements, and glucose storage (S) was obtained as the difference between total glucose disposal (M) and O. Two-way analysis of variance with interaction term demonstrated 1) a significant increase for M with hyperglycemia and a decrease with Intralipid; no interaction, and 2) in euglycemia, O/M and S/M occurred in one-to-one ratios; on the other hand, during 150-mg/dl hyperglycemia, the ratio dropped roughly to 1:2. Intralipid had no effect on the ratio, and no interaction could be observed. These results suggest the existence of physiological regulatory mechanisms by which 1) the rise in plasma free fatty acid inhibits both oxidative and nonoxidative glucose disposal, and 2) the rise in glycemia stimulates predominantly nonoxidative glucose disposal.

scholarly journals Kallikrein 12 Regulates Innate Resistance of Murine Macrophages against Mycobacterium bovis Infection by Modulating Autophagy and Apoptosis

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 415 ◽  
Author(s):  
Naveed Sabir ◽  
Tariq Hussain ◽  
Yi Liao ◽  
Jie Wang ◽  
Yinjuan Song ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Bovis ◽  
Serine Proteases ◽  
New Paradigm ◽  
Murine Macrophages ◽  
Immune Response Regulation ◽  
The Difference

Mycobacterium bovis (M. bovis) is a member of the Mycobacterium tuberculosis (Mtb) complex causing bovine tuberculosis (TB) and imposing a high zoonotic threat to human health. Kallikreins (KLKs) belong to a subgroup of secreted serine proteases. As their role is established in various physiological and pathological processes, it is likely that KLKs expression may mediate a host immune response against the M. bovis infection. In the current study, we report in vivo and in vitro upregulation of KLK12 in the M. bovis infection. To define the role of KLK12 in immune response regulation of murine macrophages, we produced KLK12 knockdown bone marrow derived macrophages (BMDMs) by using siRNA transfection. Interestingly, the knockdown of KLK12 resulted in a significant downregulation of autophagy and apoptosis in M. bovis infected BMDMs. Furthermore, we demonstrated that this KLK12 mediated regulation of autophagy and apoptosis involves mTOR/AMPK/TSC2 and BAX/Bcl-2/Cytochrome c/Caspase 3 pathways, respectively. Similarly, inflammatory cytokines IL-1β, IL-6, IL-12 and TNF-α were significantly downregulated in KLK12 knockdown macrophages but the difference in IL-10 and IFN-β expression was non-significant. Taken together, these findings suggest that upregulation of KLK12 in M. bovis infected murine macrophages plays a substantial role in the protective immune response regulation by modulating autophagy, apoptosis and pro-inflammatory pathways. To our knowledge, this is the first report on expression and the role of KLK12 in the M. bovis infection and the data may contribute to a new paradigm for diagnosis and treatment of bovine TB.

Safflower Yellow Prevents Pulmonary Metastasis of Breast Cancer by Inhibiting Tumor Cell Invadopodia

2016 ◽  
Vol 44 (07) ◽  
pp. 1491-1506 ◽  
Author(s):  
Huiying Fu ◽  
Renjie Wu ◽  
Yuanyuan Li ◽  
Lizong Zhang ◽  
Xiaofang Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Pulmonary Metastasis ◽  
Breast Cancer Cells ◽  
Dependent Cell ◽  
Response Profiles ◽  
Dose Dependent

Carthamus tinctorius L. is a traditional Chinese medicine that activates blood circulation and dissipates blood stasis, and has been extensively used as antitumor treatment in a clinical setting in single or in compound preparation form. However, empirical evidence and a better understanding of the possible mechanisms involved are still required. Here, we investigated the role of safflower yellow (SY), the active ingredient of C. tinctorius, in the pulmonary metastasis of breast cancer, and the underlying mechanism of action. EGF-meditated time- and dose-dependent cell response profiles were applied to screen for the activity of SY in vitro, while orthotopic lung metastasis and intravenous injection were used to evaluate the antimetastatic role of SY in vivo. SY could dose-dependently inhibit EGF-mediated time- and dose-dependent cell response profiles by inhibiting cytoskeletal rearrangement. We also found that SY significantly inhibited the migration of breast cancer cells in vitro and pulmonary metastasis of breast cancer cells in vivo. Consistent with these phenotypes, formation of invadopodia and the expression of MMP-9 and p-Src proteins were decreased after EGF stimulation in MBA-MD-231 cells treat with SY, as well as in lung metastatic foci. Additionally, circulating tumor cells retained in lung capillaries were also reduced. These results suggest that the antimetastatic effect of SY is due to its inhibition of invadopodia formation, which occurs mainly through Src-dependent cytoskeleton rearrangement. We suggest that SY should be considered as a potential novel therapeutic agent for the treatment of breast cancer.

scholarly journals SMAD1/5 Signaling in the Early Equine Placenta Regulates Trophoblast Differentiation and Chorionic Gonadotropin Secretion

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 3054-3064 ◽  
Author(s):  
Victoria Cabrera-Sharp ◽  
Jordan E. Read ◽  
Stephanie Richardson ◽  
Alycia A. Kowalski ◽  
Douglas F. Antczak ◽  
...  
Keyword(s):  
Chorionic Gonadotropin ◽  
Trophoblast Cells ◽  
Rt Pcr ◽  
Trophoblast Differentiation ◽  
Gonadotropin Secretion ◽  
Morphogenetic Protein ◽  
Dose Dependent

TGFβ superfamily proteins, acting via SMAD (Sma- and Mad-related protein)2/3 pathways, regulate placental function; however, the role of SMAD1/5/8 pathway in the placenta is unknown. This study investigated the functional role of bone morphogenetic protein (BMP)4 signaling through SMAD1/5 in terminal differentiation of primary chorionic gonadotropin (CG)-secreting trophoblast. Primary equine trophoblast cells or placental tissues were isolated from day 27–34 equine conceptuses. Detected by microarray, RT-PCR, and quantitative RT-PCR, equine chorionic girdle trophoblast showed increased gene expression of receptors that bind BMP4. BMP4 mRNA expression was 20- to 60-fold higher in placental tissues adjacent to the chorionic girdle compared with chorionic girdle itself, suggesting BMP4 acts primarily in a paracrine manner on the chorionic girdle. Stimulation of chorionic girdle-trophoblast cells with BMP4 resulted in a dose-dependent and developmental stage-dependent increase in total number and proportion of terminally differentiated binucleate cells. Furthermore, BMP4 treatment induced non-CG-secreting day 31 chorionic girdle trophoblast cells to secrete CG, confirming a specific functional response to BMP4 stimulation. Inhibition of SMAD2/3 signaling combined with BMP4 treatment further enhanced differentiation of trophoblast cells. Phospho-SMAD1/5, but not phospho-SMAD2, expression as determined by Western blotting was tightly regulated during chorionic girdle trophoblast differentiation in vivo, with peak expression of phospho-SMAD1/5 in vivo noted at day 31 corresponding to maximal differentiation response of trophoblast in vitro. Collectively, these experiments demonstrate the involvement of BMP4-dependent pathways in the regulation of equine trophoblast differentiation in vivo and primary trophoblast differentiation in vitro via activation of SMAD1/5 pathway, a previously unreported mechanism of TGFβ signaling in the mammalian placenta.

scholarly journals Wnt/beta-catenin signalling is dispensable for adult neural stem cell homeostasis and activation

2020 ◽  
Author(s):  
Sophie H. L. Austin ◽  
Lachlan Harris ◽  
Oana Paun ◽  
Piero Rigo ◽  
François Guillemot ◽  
...  
Keyword(s):  
Stem Cell ◽  
Beta Catenin ◽  
Dependent Manner ◽  
Direct Role ◽  
Adult Nscs ◽  
Hippocampal Networks ◽  
Dose Dependent

AbstractAdult mouse hippocampal neural stem cells (NSCs) generate new neurons that integrate into existing hippocampal networks and modulate mood and memory. These NSCs are largely quiescent and are stimulated by niche signals to activate and produce neurons. Wnt/β-catenin signalling acts at different steps along the hippocampal neurogenic lineage and has been shown to promote the proliferation of intermediate progenitor cells. However, whether it has a direct role in the regulation of NSCs still remains unclear. Here we used Wnt/β-catenin reporters and transcriptomic data from in vivo and in vitro models to show that both active and quiescent adult NSCs respond to Wnt/β-catenin signalling. Wnt/β-catenin stimulation instructed neuronal differentiation of active NSCs and promoted the activation or differentiation of quiescent NSCs in a dose-dependent manner. However, we found that inhibiting NSCs response to Wnt, by conditionally deleting β-catenin, did not affect their activation or maintenance of their stem cell characteristics. Together, our results indicate that whilst NSCs do respond to Wnt/β-catenin stimulation in a dose-dependent and state-specific manner, Wnt/β-catenin signalling is not cell-autonomously required to maintain NSC homeostasis, which could reconcile some of the contradictions in the literature as to the role of Wnt/β-catenin signalling in adult hippocampal NSCs.

scholarly journals Evolutionarily ancient role of cholecystokinin-type neuropeptide signalling as an inhibitory regulator of feeding-related processes revealed in an echinoderm

2020 ◽  
Author(s):  
Ana B. Tinoco ◽  
Antón Barreiro-Iglesias ◽  
Luis Alfonso Yañez-Guerra ◽  
Jérôme Delroisse ◽  
Ya Zhang ◽  
...  
Keyword(s):  
Body Wall ◽  
Oral Feeding ◽  
Cardiac Stomach ◽  
First Time ◽  
Dose Dependent ◽  
Type Receptor ◽  
Tube Feet

AbstractCholecystokinin (CCK) / sulfakinin (SK)-type neuropeptides regulate feeding and digestion in chordates and protostomes (e.g. insects). Here we characterised CCK/SK-type signalling for the first time in a non-chordate deuterostome - the starfish Asterias rubens (phylum Echinodermata). In this species, two neuropeptides (ArCCK1, ArCCK2) derived from the precursor protein ArCCKP act as ligands for a CCK/SK-type receptor (ArCCKR) and are expressed in the nervous system, digestive system, tube feet and body wall. Furthermore, ArCCK1 and ArCCK2 cause dose-dependent contraction of cardiac stomach, tube foot and body wall apical muscle preparations in vitro and injection of these neuropeptides in vivo triggers cardiac stomach retraction and inhibition of the onset of feeding in A. rubens. Thus, an evolutionarily ancient role of CCK/SK-type neuropeptides as inhibitory regulators of feeding-related processes in the Bilateria has been conserved in the unusual and unique context of the extra-oral feeding behaviour and pentaradial body plan of an echinoderm.

scholarly journals Ancient role of sulfakinin/cholecystokinin-type signalling in inhibitory regulation of feeding processes revealed in an echinoderm

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ana B Tinoco ◽  
Antón Barreiro-Iglesias ◽  
Luis Alfonso Yañez Guerra ◽  
Jérôme Delroisse ◽  
Ya Zhang ◽  
...  
Keyword(s):  
Oral Feeding ◽  
Cardiac Stomach ◽  
First Time ◽  
Dose Dependent ◽  
Type Receptor ◽  
Tube Feet ◽  
Inhibitory Regulation

Sulfakinin (SK)/cholecystokinin (CCK)-type neuropeptides regulate feeding and digestion in protostomes (e.g. insects) and chordates. Here, we characterised SK/CCK-type signalling for the first time in a non-chordate deuterostome – the starfish Asterias rubens (phylum Echinodermata). In this species, two neuropeptides (ArSK/CCK1, ArSK/CCK2) derived from the precursor protein ArSK/CCKP act as ligands for an SK/CCK-type receptor (ArSK/CCKR) and these peptides/proteins are expressed in the nervous system, digestive system, tube feet, and body wall. Furthermore, ArSK/CCK1 and ArSK/CCK2 cause dose-dependent contraction of cardiac stomach, tube foot, and apical muscle preparations in vitro, and injection of these neuropeptides in vivo triggers cardiac stomach retraction and inhibition of the onset of feeding in A. rubens. Thus, an evolutionarily ancient role of SK/CCK-type neuropeptides as inhibitory regulators of feeding-related processes in the Bilateria has been conserved in the unusual and unique context of the extra-oral feeding behaviour and pentaradial body plan of an echinoderm.

scholarly journals Postsynaptic density protein 95 (PSD-95) is transported by KIF5 to dendritic regions

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Ki-Seo Yoo ◽  
Kina Lee ◽  
Jun-Young Oh ◽  
Hyoeun Lee ◽  
Hyungju Park ◽  
...  
Keyword(s):  
Pdz Domain ◽  
Postsynaptic Density ◽  
Scaffolding Protein ◽  
Synaptic Localization ◽  
Conventional Kinesin ◽  
Dose Dependent ◽  
Postsynaptic Density Protein

AbstractPostsynaptic density protein 95 (PSD-95) is a pivotal postsynaptic scaffolding protein in excitatory neurons. Although the transport and regulation of PSD-95 in synaptic regions is well understood, dendritic transport of PSD-95 before synaptic localization still remains to be clarified. To evaluate the role of KIF5, conventional kinesin, in the dendritic transport of PSD-95 protein, we expressed a transport defective form of KIF5A (ΔMD) that does not contain the N-terminal motor domain. Expression of ΔMD significantly decreased PSD-95 level in the dendrites. Consistently, KIF5 was associated with PSD-95 in in vitro and in vivo assays. This interaction was mediated by the C-terminal tail regions of KIF5A and the third PDZ domain of PSD-95. Additionally, the ADPDZ3 (the association domain of NMDA receptor and PDZ3 domain) expression significantly reduced the levels of PSD-95, glutamate receptor 1 (GluA1) in dendrites. The association between PSD-95 and KIF5A was dose-dependent on Staufen protein, suggesting that the Staufen plays a role as a regulatory role in the association. Taken together, our data suggest a new mechanism for dendritic transport of the AMPA receptor-PSD-95.

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