MODIFICATION OF THE MINIMAL BERGMAN MODEL OF THE "INSULIN-GLUCOSE" SYSTEM AND ITS IMPLEMENTATION IN MATLAB/SIMULINK

The article discusses a modification of Bergman's minimal mathematical model of the "insulin-glucose" system, which allows simulating controlled exogenous sources of glucose and insulin into the patient's blood on the model and investigating the dynamics of changes in their concentrations in normal conditions, in type I DM and type II DM. A modeling scheme is presented in graphic notations of the MatLab / Simulink computer mathematics system and a number of computational experiments on it are described to determine the type of glycemic profiles of glucose and insulin concentration in the patient's blood in the noted situations. The fundamental possibility of using model mappings in the MatLab/Simulink environment for the study and tuning of the loop for automatic regulation of the "insulin-glucose" balance in the patient's blood using a controlled insulin pump is demonstrated. It was also found that the modified minimal model can be customized for a specific patient with diabetes, which makes it possible to use it to solve the problems of individual prediction of the development of a diabetic disease in a specific patient. In addition, the described model makes it possible to recreate and virtually investigate various conditions and cases on it that affect the dynamics of insulin and glucose concentrations in the patient's blood, for example, when he performs physically stressed activities, in the presence of the effects of “aging” of insulin-producing cells in the pancreas. iron, etc.

Minimal and Maximal Models to Quantitate Glucose Metabolism: Tools to Measure, to Simulate and to Run in Silico Clinical Trials

Several models have been proposed to describe the glucose system at whole-body, organ/tissue and cellular level, designed to measure non-accessible parameters (minimal models), to simulate system behavior and run in silico clinical trials (maximal models). Here, we will review the authors’ work, by putting it into a concise historical background. We will discuss first the parametric portrait provided by the oral minimal models—building on the classical intravenous glucose tolerance test minimal models—to measure otherwise non-accessible key parameters like insulin sensitivity and beta-cell responsivity from a physiological oral test, the mixed meal or the oral glucose tolerance tests, and what can be gained by adding a tracer to the oral glucose dose. These models were used in various pathophysiological studies, which we will briefly review. A deeper understanding of insulin sensitivity can be gained by measuring insulin action in the skeletal muscle. This requires the use of isotopic tracers: both the classical multiple-tracer dilution and the positron emission tomography techniques are discussed, which quantitate the effect of insulin on the individual steps of glucose metabolism, that is, bidirectional transport plasma-interstitium, and phosphorylation. Finally, we will present a cellular model of insulin secretion that, using a multiscale modeling approach, highlights the relations between minimal model indices and subcellular secretory events. In terms of maximal models, we will move from a parametric to a flux portrait of the system by discussing the triple tracer meal protocol implemented with the tracer-to-tracee clamp technique. This allows to arrive at quasi-model independent measurement of glucose rate of appearance (Ra), endogenous glucose production (EGP), and glucose rate of disappearance (Rd). Both the fast absorbing simple carbs and the slow absorbing complex carbs are discussed. This rich data base has allowed us to build the UVA/Padova Type 1 diabetes and the Padova Type 2 diabetes large scale simulators. In particular, the UVA/Padova Type 1 simulator proved to be a very useful tool to safely and effectively test in silico closed-loop control algorithms for an artificial pancreas (AP). This was the first and unique simulator of the glucose system accepted by the U.S. Food and Drug Administration as a substitute to animal trials for in silico testing AP algorithms. Recent uses of the simulator have looked at glucose sensors for non-adjunctive use and new insulin molecules.

Antiglycative and anti-inflammatory effects of lipophilized tyrosol derivatives

To expand the application of tyrosol, a series of lipophilized tyrosol derivatives were synthesized via esterification of tyrosol with fatty acids of different chain lengths. The antiglycative activity of tyrosol esters so prepared was subsequently examined in the bovine serum albumin/glucose system. A quasi-parabolic shape was observed when the activity was plotted against alkyl chain length. Additionally, the anti-inflammatory effects of these derivatives were evaluated against methylglyoxal-induced inflammation in RAW264.7 cells. The same trend on anti-inflammatory activity was found as in the antiglycation study. The results showed that tyrosol esters with C12:0 and C14:0 were two most efficient ones among all the tested derivatives. Thus, some lipophilized tyrosol derivatives were stronger antiglycative and anti-inflammatory agents compared to the parent compound, tyrosol. Graphical abstract

Effective continuous acetone–butanol–ethanol production with full utilization of cassava by immobilized symbiotic TSH06

Background Butanol production by fermentation has recently attracted increasingly more attention because of its mild reaction conditions and environmentally friendly properties. However, traditional feedstocks, such as corn, are food supplies for human beings and are expensive and not suitable for butanol production at a large scale. In this study, acetone, butanol, and ethanol (ABE) fermentation with non-pretreated cassava using a symbiotic TSH06 was investigated. Results In batch fermentation, the butanol concentration of 11.6 g/L was obtained with a productivity of 0.16 g/L/h, which was similar to that obtained from glucose system. A full utilization system of cassava was constructed to improve the fermentation performance, cassava flour was used as the substrate and cassava peel residue was used as the immobilization carrier. ABE fermentation with immobilized cells resulted in total ABE and butanol concentrations of 20 g/L and 13.3 g/L, which were 13.6% and 14.7% higher, respectively, than those of free cells. To further improve the solvent productivity, continuous fermentation was conducted with immobilized cells. In single-stage continuous fermentation, the concentrations of total ABE and butanol reached 9.3 g/L and 6.3 g/L with ABE and butanol productivities of 1.86 g/L/h and 1.26 g/L/h, respectively. In addition, both of the high product concentration and high solvent productivity were achieved in a three-stage continuous fermentation. The ABE productivity and concentration was 1.12 g/L/h and 16.8 g/L, respectively. Conclusions The results indicate that TSH06 could produce solvents from cassava effectively. This study shows that ABE fermentation with cassava as a substrate could be an efficient and economical method of butanol production.

Assessing quality of glycemic control: Hypo- and hyperglycemia, and glycemic variability using mobile self-monitoring of blood glucose system

Although mobile applications bring potential benefits of metabolic control for patients with diabetes, their effect on glycemic fluctuation has been less widely explored. The goal of this study was to utilize data from the Mobile Self-Monitoring of Blood Glucose System to obtain a picture of the metabolic progression. Twenty-seven adults with type 2 diabetes mellitus were recruited to receive a mobile diabetes self-care system for a six-week period. The approach to the interpretation of glycemic control patterns, utilizes the following methods: 1) Graphical displays of the percentage of hyper-and-hypoglycemia episodes; 2) Pattern recognition of glycemic variability based on a simple equation involving both the standard deviation and the mean. Analytical results reveal that short-term usage of the developed system stabilizes the week-by-week glycemic fluctuations. Four categories were established to distinguish different patterns of patients’ glycemic variation. If patterns of glycemic control can be recognized or interpreted by newly designed mobile applications, then the collection and analysis of metabolic variation will greatly help both health care providers and patients in effective diabetes management.

Antioxidant Activity and In Vitro Antiglycation of the Fruit of Spondias purpurea

Hyperglycemia in diabetes mellitus causes irreversible life-threatening micro- and macrovascular complications. There is evidence that the glycation reaction leads to a chemical modification of the proteins contributing to the complications of diabetes. It is known that advanced glycation end products (AGEs) are formed by glycation and oxidation reactions called glycoxidation. CML, a nonfluorescent AGE, has become a biomarker of glycoxidative damage; other AGEs appear to induce oxidative stress, which results in cytotoxicity. To determine antioxidant activity, the FRAP, DPPH, and TEAC tests were used, as well as the polyphenols content using Folin-Ciocalteu’s method. To evaluate the antiglycation activity, the BSA/glucose system was used, and the fructosamine concentration, protein carbonyl content, thiol, and CML groups were determined. The results obtained show that the hexane extract of the fruit of Spondias purpurea (CFH) effectively inhibits the glycation reaction, in addition to increasing the thiol groups and decreasing levels of fructosamine, protein carbonyl, and CML. In addition, CFH presented significant antioxidant activity. CFH inhibits the glycation reaction; therefore, it can help prevent complications related to AGEs in diabetes mellitus; it also reduces oxidative stress and is effective in protecting proteins from oxidative damage.