Enzyme kinetic approach for mechanistic insight and predictions of in vivo starch digestibility and the glycaemic index of foods

During processing of cereal-based food products, starch undergoes dramatic changes. The objective of this work was to evaluate the impact of food processing on the starch digestibility profile of cereal-based foods using advanced imaging techniques, and to determine the effect of preserving starch in its native, slowly digestible form on its in vivo metabolic fate. Four different food products using different processing technologies were evaluated: extruded products, rusks, soft-baked cakes, and rotary-molded biscuits. Imaging techniques (X-ray diffraction, micro-X-ray microtomography, and electronic microscopy) were used to investigate changes in slowly digestible starch (SDS) structure that occurred during these different food processing technologies. For in vivo evaluation, International Standards for glycemic index (GI) methodology were applied on 12 healthy subjects. Rotary molding preserved starch in its intact form and resulted in the highest SDS content (28 g/100 g) and a significantly lower glycemic and insulinemic response, while the three other technologies resulted in SDS contents below 3 g/100 g. These low SDS values were due to greater disruption of the starch structure, which translated to a shift from a crystalline structure to an amorphous one. Modulation of postprandial glycemia, through starch digestibility modulation, is a meaningful target for the prevention of metabolic diseases.

Download Full-text

Measurement of rapidly available glucose (RAG) in plant foods: a potential in vitro predictor of the glycaemic response

British Journal Of Nutrition ◽

10.1079/bjn19960137 ◽

1996 ◽

Vol 75 (3) ◽

pp. 327-337 ◽

Cited By ~ 209

Author(s):

Hans N Englyst ◽

Jan Veenstra ◽

Geoffrey J Hudson

Keyword(s):

Small Intestine ◽

Direct Calculation ◽

Simple Calculation ◽

Glycaemic Index ◽

Equal Weight ◽

Glycaemic Response ◽

Human Small Intestine ◽

Reference Amount

AbstractThe glycaemic index (GI) is an in vivo measurement based on the glycaemicresponse to carbohydrate-containing foods, and allows foods to be ranked on the basis of the rate of digestion and absorption of the carbohydrates that they contain. GI values are normalizedto a reference amount of available carbohydrate and do not reflect the amounts of carbohydrate normally present in foods; for example, a food with a low content of carbohydrates will have a high GI value if that carbohydrate is digested and absorbed rapidly in the human small intestine. This is potentially confusing for a person wishing to control his or her blood glucoselevels by the choice of foods. The rate and extent of starch digestion in vitro has been measured using a technique that classifies starch into three major fractions: rapidly digestible starch (RDS), slowly digestible starch (SDS) and resistant starch (RS). In addition, thistechnique gives a value for rapidly available glucose (RAG), which includes RDS, free glucose and the glucose moiety of sucrose. When the values for thirty-nine foods were expressed on the basis ofthe available carbohydrate content of these foods, highly significant (P<0·001) positive correlations were observed between GI and both RDS and RAG. The measurement of RAGin vitro provides values for direct calculation of the amount of glucose likely to be rapidly absorbed in the human small intestine and,thus, to influence blood glucose and insulin levels. These values can be used to compare foods, as eaten,on an equal-weight basis. Food-table RAG values would allow simple calculation of the total amount of RAG provided by single foods, by whole meals and by whole diets. Studies are planned in which RAG and the glycaemic response in man will be measured for identical food products.

Download Full-text

SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling

10.1101/2021.12.10.472112 ◽

2021 ◽

Author(s):

Scott B Biering ◽

Francielle Tramontini Gomes de Sousa ◽

Laurentia V. Tjang ◽

Felix Pahmeier ◽

Richard Ruan ◽

...

Keyword(s):

Transcriptional Response ◽

Barrier Dysfunction ◽

Vascular Leak ◽

Endothelial Barrier Dysfunction ◽

Mechanistic Insight ◽

Starting Point ◽

Signaling Axis ◽

Insight Into

Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction within the lung as well as in distal organs. While it is appreciated that an exaggerated inflammatory response is associated with barrier dysfunction, the triggers of this pathology are unclear. Here, we report that cell-intrinsic interactions between the Spike (S) glycoprotein of SARS-CoV-2 and epithelial/endothelial cells are sufficient to trigger barrier dysfunction in vitro and vascular leak in vivo, independently of viral replication and the ACE2 receptor. We identify an S-triggered transcriptional response associated with extracellular matrix reorganization and TGF-β signaling. Using genetic knockouts and specific inhibitors, we demonstrate that glycosaminoglycans, integrins, and the TGF-β signaling axis are required for S-mediated barrier dysfunction. Our findings suggest that S interactions with barrier cells are a contributing factor to COVID-19 disease severity and offer mechanistic insight into SARS-CoV-2 triggered vascular leak, providing a starting point for development of therapies targeting COVID-19 pathogenesis.

Download Full-text

In Vivo and In Vitro Starch Digestibility of Fresh Pasta Produced Using Semolina-Based or Wholemeal Semolina-Based Liquid Sourdough

Foods ◽

10.3390/foods10102507 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2507

Author(s):

Simonetta Fois ◽

Piero Pasqualino Piu ◽

Manuela Sanna ◽

Tonina Roggio ◽

Pasquale Catzeddu

Keyword(s):

Glycemic Load ◽

Health Benefits ◽

Starch Digestibility ◽

Glycemic Response ◽

In Vitro Starch Digestibility ◽

Food Matrices ◽

Fresh Pasta

The use of wholemeal flour and sourdough fermentation in different food matrices has received considerable attention in recent years due to its resulting health benefits. In this study, a semolina-based and a wholemeal semolina-based sourdough were prepared and added to the formulation of gnocchetti-type fresh pasta. Four types of gnocchetti were made, using semolina plus semolina-based sourdough (SS), semolina plus wholemeal semolina-based sourdough (SWS), semolina alone (S), and semolina plus wholemeal semolina (WS). The latter two were used as controls. The digestibility of starch was studied both in vitro and in vivo, and the glycemic response (GR) and glycemic load (GL) were determined. Starch digestibility, both in vivo and in vitro, was higher in wholemeal semolina than semolina pasta and the resulting GR values (mg dL−1 min−1) were also higher (2209 and 2277 for WS and SWS; 1584 and 1553 for S and SS, respectively). The use of sourdough significantly reduced the rapidly digestible starch (RDS) content and increased the inaccessible digestible starch (IDS) content. The addition of sourdough to the formulation had no effect on the GR values, but led to a reduction of the GL of the pasta. These are the first data on the GR and GL of fresh pasta made with sourdough.

Download Full-text

Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling

European Journal of Pharmaceutical Sciences ◽

10.1016/s0928-0987(00)00146-9 ◽

2000 ◽

Vol 12 (2) ◽

pp. 117-124 ◽

Cited By ~ 30

Author(s):

Jan J.P. Bogaards ◽

Erna M. Hissink ◽

Mike Briggs ◽

Richard Weaver ◽

Roeline Jochemsen ◽

...

Keyword(s):

Kinetic Data ◽

Interindividual Variation ◽

Enzyme Kinetic ◽

Physiologically Based Pharmacokinetic Modeling ◽

Physiologically Based Pharmacokinetic ◽

Drug Plasma ◽

Physiologically Based ◽

Drug Plasma Levels ◽

Individual Enzyme

Download Full-text

Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation

Nature Communications ◽

10.1038/s41467-019-12551-5 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 4

Author(s):

Brianna J. Klein ◽

Suk Min Jang ◽

Catherine Lachance ◽

Wenyi Mi ◽

Jie Lyu ◽

...

Keyword(s):

Posttranslational Modification ◽

Memory Impairment ◽

Target Genes ◽

Epigenetic Mark ◽

Mechanistic Insight ◽

Genomic Analyses ◽

Insight Into

Abstract Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransferase and elucidate its mechanism of action. The acetyltransferase function of the catalytic MORF subunit is positively regulated by the DPF domain of MORF (MORFDPF). The crystal structure of MORFDPF in complex with crotonylated H3K14 peptide provides mechanistic insight into selectivity of this epigenetic reader and its ability to recognize both histone and DNA. ChIP data reveal the role of MORFDPF in MORF-dependent H3K23 acetylation of target genes. Mass spectrometry, biochemical and genomic analyses show co-existence of the H3K23ac and H3K14ac modifications in vitro and co-occupancy of the MORF complex, H3K23ac, and H3K14ac at specific loci in vivo. Our findings suggest a model in which interaction of MORFDPF with acylated H3K14 promotes acetylation of H3K23 by the native MORF complex to activate transcription.

Download Full-text

Can Manipulation of Durum Wheat Amylose Content Reduce the Glycaemic Index of Spaghetti?

Foods ◽

10.3390/foods9060693 ◽

2020 ◽

Vol 9 (6) ◽

pp. 693 ◽

Cited By ~ 1

Author(s):

Mike Sissons ◽

Francesco Sestili ◽

Ermelinda Botticella ◽

Stefania Masci ◽

Domenico Lafiandra

Keyword(s):

Durum Wheat ◽

Wheat Cultivar ◽

Amylose Content ◽

Fold Increase ◽

Glycaemic Index ◽

Glycaemic Response ◽

Branching Enzymes ◽

Lifestyle Diseases

Resistant starch (RS) in foods has positive benefits for potentially alleviating lifestyle diseases. RS is correlated positively with starch amylose content. This study aimed to see what level of amylose in durum wheat is needed to lower pasta GI. The silencing of starch synthases IIa (SSIIa) and starch branching enzymes IIa (SBEIIa), key genes involved in starch biosynthesis, in durum wheat cultivar Svevo was performed and spaghetti was prepared and evaluated. The SSIIa and SBEIIa mutants have a 28% and 74% increase in amylose and a 2.8- and 35-fold increase in RS, respectively. Cooked pasta was softer, with higher cooking loss but lower stickiness compared to Svevo spaghetti, and with acceptable appearance and colour. In vitro starch digestion extent (area under the digestion curve) was decreased in both mutants, but much more in SBEIIa, while in vivo GI was only significantly reduced from 50 to 38 in SBEIIa. This is the first study of the glycaemic response of spaghetti prepared from SBEIIa and SSIIa durum wheat mutants. Overall pasta quality was acceptable in both mutants but the SBEIIa mutation provides a clear glycaemic benefit and would be much more appealing than wholemeal spaghetti. We suggest a minimum RS content in spaghetti of ~7% is needed to lower GI which corresponded to an amylose content of ~58%.

Download Full-text