Effects of intraduodenal infusions of L-phenylalanine and L-glutamine on antropyloroduodenal motility and plasma cholecystokinin in healthy men

BACKGROUND/AIMS Dietary proteins have potent eating-inhibitory and glucose-lowering effects, which may be mediated via effects of amino acids on gastrointestinal hormone and motor function, although little information is available. We have now evaluated the effects of L-phenylalanine (L-Phe) and L-glutamine (L-Gln) on antropyloroduodenal motility and plasma cholecystokinin (CCK) concentrations. METHODS Two double-blind, 3-way cross-over studies were performed, each including 10 healthy, normal-weight men. We determined the antropyloroduodenal motor and plasma CCK responses to 90-minute intraduodenal infusions of L-Phe (study A) or L-Gln (study B), each at 0.15 kcal/min (total 13.5 kcal), or 0.45 kcal/min (total 40.5 kcal), or saline (control), in randomized fashion. RESULTS Intraduodenal L-Phe at 0.45 kcal/min, but not at 0.15 kcal/min, suppressed antral (P < 0.01), and stimulated phasic (P < 0.01), but not tonic, pyloric, or duodenal pressures, while L-Phe at both 0.15 kcal/min and 0.45 kcal/min stimulated plasma CCK. In contrast, L-Gln had no effect on antral, duodenal or pyloric pressures, or plasma CCK. CONCLUSIONS Intraduodenal infusions of L-Phe and L-Gln, in doses of 0.15 kcal/min and 0.45 kcal/min for 90 minutes, have different effects on antropyloroduodenal motility and CCK in normal-weight men. The modulation of antral and pyloric pressures and CCK may contribute to the eating-inhibitory effects of oral L-Phe, possibly through the slowing of gastric emptying.Robert E Steinert, Maria F Landrock, Michael Horowitz, and Christine Feinle-Bisse

Contributions of upper gut hormones and motility to the energy intake-suppressant effects of intraduodenal nutrients in healthy, lean men - a pooled-data analysis

Accepted: 8 August 2016We have previously identified pyloric pressures and plasma cholecystokinin (CCK) concentrations as independent determinants of energy intake following administration of intraduodenal lipid and intravenous CCK. We evaluated in healthy men whether these parameters also determine energy intake in response to intraduodenal protein, and whether, across the nutrients, any predominant gastrointestinal (GI) factors exist, or many factors make small contributions. Data from nine published studies, in which antropyloroduodenal pressures, GI hormones, and GI /appetite perceptions were measured during intraduodenal lipid or protein infusions, were pooled. In all studies energy intake was quantified immediately after the infusions. Specific variables for inclusion in a mixed-effects multivariable model for determination of independent predictors of energy intake were chosen following assessment for collinearity, and within-subject correlations between energy intake and these variables were determined using bivariate analyses adjusted for repeated measures. In models based on all studies, or lipid studies, there were significant effects for amplitude of antral pressure waves, premeal glucagon-like peptide-1 (GLP-1) and time-to-peak GLP-1 concentrations, GLP-1 AUC and bloating scores (P < 0.05), and trends for basal pyloric pressure (BPP), amplitude of duodenal pressure waves, peak CCK concentrations, and hunger and nausea scores (0.05 < P ≤ 0.094), to be independent determinants of subsequent energy intake. In the model including the protein studies, only BPP was identified as an independent determinant of energy intake (P < 0.05). No single parameter was identified across all models, and effects of the variables identified were relatively small. Taken together, while GI mechanisms contribute to the regulation of acute energy intake by lipid and protein, their contribution to the latter is much less. Moreover, the effects are likely to reflect small, cumulative contributions from a range of interrelated factors.Gudrun Schober, Kylie Lange, Robert E. Steinert, Amy T. Hutchison, Natalie D. Luscombe-Marsh, Maria F. Landrock, Michael Horowitz, Radhika V. Seimon and Christine Feinle-Bisse

Selective Cholesterol Dynamics between Lipoproteins and Caveolae/Lipid Rafts

Although low-density lipoprotein (LDL) receptor-mediated cholesterol uptake through clathrin-coated pits is now well understood, the molecular details and organizing principles for selective cholesterol uptake/efflux (reverse cholesterol transport, RCT) from peripheral cells remain to be resolved. It is not yet completely clear whether RCT between serum lipoproteins and the plasma membrane occurs primarily through lipid rafts/caveolae or from non-raft domains. To begin to address these issues, lipid raft/caveolae-, caveolae-, and non-raft-enriched fractions were resolved from purified plasma membranes isolated from L-cell fibroblasts and MDCK cells by detergent-free affinity chromatography and compared with detergent-resistant membranes isolated from the same cells. Fluorescent sterol exchange assays between lipoproteins (VLDL, LDL, HDL, apoA1) and these enriched domains provided new insights into supporting the role of lipid rafts/caveolae and caveolae in plasma membrane/lipoprotein cholesterol dynamics:  (i) lipids known to be translocated through caveolae were detected (cholesteryl ester, triacylglycerol) and/or enriched (cholesterol, phospholipid) in lipid raft/caveolae fractions; (ii) lipoprotein-mediated sterol uptake/efflux from lipid rafts/caveolae and caveolae was rapid and lipoprotein specific, whereas that from non-rafts was very slow and independent of lipoprotein class; and (iii) the rate and lipoprotein specificity of sterol efflux from lipid rafts/caveolae or caveolae to lipoprotein acceptors in vitro was slower and differed in specificity from that in intact cellsconsistent with intracellular factors contributing significantly to cholesterol dynamics between the plasma membrane and lipoproteins

Co-Administration of Injected and Oral Vaccine Candidates Elicits Improved Immune Responses over Either Route Alone

Infectious diseases continue to be a significant cause of morbidity and mortality, and although efficacious vaccines are available for many diseases, some parenteral vaccines elicit little or no mucosal antibodies which can be a significant problem since mucosal tissue is the point of entry for 90% of pathogens. In order to provide protection for both serum and mucosal areas, we have tested a combinatorial approach of both parenteral and oral administration of antigens for diseases caused by a viral pathogen, Hepatitis B, and a fungal pathogen, Coccidioides. We demonstrate that co-administration by the parenteral and oral routes is a useful tool to increase the overall immune response. This can include achieving an immune response in tissues that are not elicited when using only one route of administration, providing a higher level of response that can lead to fewer required doses or possibly providing a better response for individuals that are considered poor or non-responders

The structure of blocks with a Klein four defect group

We prove Erdmann’s conjecture [16] stating that every block with a Klein four defect group has a simple module with trivial source, and deduce from this that Puig’s finiteness conjecture holds for source algebras of blocks with a Klein four defect group. The proof uses the classification of finite simple groups

Filtered multiplicative bases of restricted enveloping algebras

We study the problem of the existence of filtered multiplicative bases of a restricted enveloping algebra u(L), where L is a finite-dimensional and p-nilpotent restricted Lie algebra over a field of positive characteristic p

SCP-2/SCP-x gene ablation alters lipid raft domains in primary cultured mouse hepatocytes

Although reverse cholesterol transport from peripheral cell types is mediated through plasma membrane microdomains termed lipid rafts, almost nothing is known regarding the existence, protein/lipid composition, or structure of these putative domains in liver hepatocytes, cells responsible for the net removal of cholesterol from the body. Lipid rafts purified from hepatocyte plasma membranes by a nondetergent affinity chromatography method were