Logical design of oral glucose ingestion pattern minimizing blood glucose in humans

Fujii, Masashi; Murakami, Yohei; Karasawa, Yasuyuki; Sumitomo, Yohei; Fujita, Suguru; Koyama, Masanori; Uda, Shinsuke; Konishi, Hiroyuki; Inoue, Hiroshi; Konishi, Kazuo; Oba, Shigeyuki; Ishii, Shin; Kuroda, Shinya

doi:10.1038/s41540-019-0108-1

Cited by 12 publications

(26 citation statements)

References 48 publications

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“…An intravenous catheter was inserted into vein of the forearm and fasting samples were drawn twice, and then a glucose solution containing 75 g glucose (TRELAN-G75 (AJINOMOTO)) or the same amount of water was orally ingested within a few minutes. Blood samples were obtained at 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 210, 240 min after ingestion as described previously 35 . Subjects remained at rest throughout the test.…”

Section: Methodsmentioning

confidence: 99%

Four features of temporal patterns characterize similarity among individuals and molecules by glucose ingestion in humans

et al. 2022

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Oral glucose ingestion induces systemic changes of many blood metabolites related not only to glucose, but also other metabolites such as amino acids and lipids through many blood hormones. However, the detailed temporal changes in the concentrations of comprehensive metabolites and hormones over a long time by oral glucose ingestion are uncharacterized. We measured 83 metabolites and 7 hormones in 20 healthy human subjects in response to glucose ingestion. We characterized temporal patterns of blood molecules by four features: (i) the decomposability into “amplitude” and “rate” components, (ii) the similarity of temporal patterns among individuals, (iii) the relation of molecules over time among individuals, and (iv) the similarity of temporal patterns among molecules. Glucose and glucose metabolism-related hormones indicated a rapid increase, and citrulline and lipids, which indicated a rapid decrease, returned to fasting levels faster than amino acids. Compared to glucose metabolism-related molecules and lipids, amino acids showed similar temporal patterns among individuals. The four features of temporal patterns of blood molecules by oral glucose ingestion characterize the differences among individuals and among molecules.

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Section: Methodsmentioning

confidence: 99%

Four features of temporal patterns characterize similarity among individuals and molecules by glucose ingestion in humans

et al. 2022

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“…For instance, with our current experimental setting, kinetics of the in vitro glucose response was considerably slower than in vivo. In our liver-pancreas MPS, glucose levels reached normoglycemia approximately 48 hours after the start of a GTT, as opposed to 1 to 2 hours in vivo (Bergman et al, 1981;Man et al, 2007;Fujii et al, 2019). This could be due to several factors including design aspects, properties of the co-culture medium and the organoids, operating conditions (e.g.…”

Section: Cd)mentioning

confidence: 84%

Integrated experimental-computational analysis of a liver-islet microphysiological system for human-centric diabetes research

Casas

Vilén²,

Bauer³

et al. 2021

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Microphysiological systems (MPS) are powerful tools for emulating human physiology and replicating disease progression in vitro. MPS could be better predictors of human outcome than current animal models, but mechanistic interpretation and in vivo extrapolation of the experimental results remain significant challenges. Here, we address these challenges using an integrated experimental-computational approach. This approach allows for in silico representation and predictions of glucose metabolism in a previously reported MPS with two organ compartments (liver and pancreas) connected in a closed loop with circulating medium. We developed a computational model describing glucose metabolism over 15 days of culture in the MPS. The model was calibrated on an experiment-specific basis using data from seven experiments, where single-liver or liver-islet cultures were exposed to both normal and hyperglycemic conditions resembling high blood glucose levels in diabetes. The calibrated models reproduced the fast (i.e. hourly) variations in glucose and insulin observed in the MPS experiments, as well as the long-term (i.e. over weeks) decline in both glucose tolerance and insulin secretion. We also investigated the behavior of the system under hypoglycemia by simulating this condition in silico, and the model could correctly predict the glucose and insulin responses measured in new MPS experiments. Last, we used the computational model to translate the experimental results to humans, showing good agreement with published data of the glucose response to a meal in healthy subjects. The integrated experimental-computational framework opens new avenues for future investigations toward disease mechanisms and the development of new therapies for metabolic disorders.

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“…In our study, the postprandial increases in blood glucose and GLP-1 levels were significantly greater in patients who underwent gastrectomy than those in the controls. GLP-1 is a GI hormone secreted from the GI tract upon meal ingestion and slows gastric emptying and intestinal motility to promote early satiety [ 18 19 20 ]. Previous studies suggested that an exaggerated early release of GLP-1 could lead to postprandial symptoms such as bloating, nausea, and anxiety, which are the main constituents of early dumping syndrome [ 8 21 ].…”

Section: Discussionmentioning

confidence: 99%

Postprandial Changes in Gastrointestinal Hormones and Hemodynamics after Gastrectomy in Terms of Early Dumping Syndrome

et al. 2020

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This study aimed to examine the early postprandial changes in gastrointestinal (GI) hormones and hemodynamics in terms of early dumping syndrome after gastrectomy for gastric cancer. Materials and Methods: Forty patients who underwent gastrectomy for gastric cancer and 18 controls without previous abdominal surgery were enrolled. Before and 20 minutes after liquid meal ingestion, blood glucose, glucagon-like peptide-1 (GLP-1), and GLP-2 concentrations and superior mesenteric artery (SMA) and renal blood flow were measured. The patients' heart rates were recorded at 5-minute intervals. All subjects were examined for dumping syndrome using a questionnaire based on Sigstad's clinical diagnostic index. Results: The postprandial increases in blood glucose, GLP-1, and GLP-2 levels as well as SMA blood flow and heart rate were greater in patients who underwent gastrectomy than in controls (all P<0.010). Patients who underwent gastrectomy showed a significantly decreased renal blood flow (P<0.001). Among patients who underwent gastrectomy, distal gastrectomy was a significant clinical factor associated with a lower risk of early dumping syndrome than total gastrectomy (hazard ratio, 0.092; 95% confidence interval, 0.013-0.649; P=0.017). Patients who underwent total gastrectomy showed a greater postprandial increase in blood glucose (P<0.001), GLP-1 (P=0.030), and GLP-2 (P=0.002) levels as well as and heart rate (P=0.013) compared to those who underwent distal gastrectomy. Conclusions: Early postprandial changes in GI hormones and hemodynamics were greater in patients who underwent gastrectomy than in controls, especially after total gastrectomy, suggesting that these changes play a crucial role in the pathophysiology of early dumping syndrome.

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Logical design of oral glucose ingestion pattern minimizing blood glucose in humans

Cited by 12 publications

References 48 publications

Four features of temporal patterns characterize similarity among individuals and molecules by glucose ingestion in humans

Four features of temporal patterns characterize similarity among individuals and molecules by glucose ingestion in humans

Integrated experimental-computational analysis of a liver-islet microphysiological system for human-centric diabetes research

Postprandial Changes in Gastrointestinal Hormones and Hemodynamics after Gastrectomy in Terms of Early Dumping Syndrome

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