Roles of interstitial fluid pH and weak organic acids in development and amelioration of insulin resistance

2021 ◽  
Author(s):  
Yoshinori Marunaka
Keyword(s):  
Insulin Resistance ◽  
Organic Acids ◽  
Binding Affinity ◽  
Interstitial Fluid ◽  
Ph Value ◽  
Insulin Binding ◽  
The Body ◽  
Weak Organic Acids ◽  
Arterial Blood ◽  
Blood Ph

Type 2 diabetes mellitus (T2DM) is one of the most common lifestyle-related diseases (metabolic disorders) due to hyperphagia and/or hypokinesia. Hyperglycemia is the most well-known symptom occurring in T2DM patients. Insulin resistance is also one of the most important symptoms, however, it is still unclear how insulin resistance develops in T2DM. Detailed understanding of the pathogenesis primarily causing insulin resistance is essential for developing new therapies for T2DM. Insulin receptors are located at the plasma membrane of the insulin-targeted cells such as myocytes, adipocytes, etc., and insulin binds to the extracellular site of its receptor facing the interstitial fluid. Thus, changes in interstitial fluid microenvironments, specially pH, affect the insulin-binding affinity to its receptor. The most well-known clinical condition regarding pH is systemic acidosis (arterial blood pH < 7.35) frequently observed in severe T2DM associated with insulin resistance. Because the insulin-binding site of its receptor faces the interstitial fluid, we should recognize the interstitial fluid pH value, one of the most important factors influencing the insulin-binding affinity. It is notable that the interstitial fluid pH is unstable compared with the arterial blood pH even under conditions that the arterial blood pH stays within the normal range, 7.35–7.45. This review article introduces molecular mechanisms on unstable interstitial fluid pH value influencing the insulin action via changes in insulin-binding affinity and ameliorating actions of weak organic acids on insulin resistance via their characteristics as bases after absorption into the body even with sour taste at the tongue.

scholarly journals The Proposal of Molecular Mechanisms of Weak Organic Acids Intake-Induced Improvement of Insulin Resistance in Diabetes Mellitus via Elevation of Interstitial Fluid pH

2018 ◽  
Vol 19 (10) ◽  
pp. 3244 ◽  
Author(s):  
Yoshinori Marunaka
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Organic Acids ◽  
Molecular Mechanism ◽  
Interstitial Fluid ◽  
Molecular Mechanisms ◽  
Salt Intake ◽  
High Salt ◽  
Weak Organic Acids ◽  
High Salt Intake

Blood contains powerful pH-buffering molecules such as hemoglobin (Hb) and albumin, while interstitial fluids have little pH-buffering molecules. Thus, even under metabolic disorder conditions except severe cases, arterial blood pH is kept constant within the normal range (7.35~7.45), but the interstitial fluid pH under metabolic disorder conditions becomes lower than the normal level. Insulin resistance is one of the most important key factors in pathogenesis of diabetes mellitus, nevertheless the molecular mechanism of insulin resistance occurrence is still unclear. Our studies indicate that lowered interstitial fluid pH occurs in diabetes mellitus, causing insulin resistance via reduction of the binding affinity of insulin to its receptor. Therefore, the key point for improvement of insulin resistance occurring in diabetes mellitus is development of methods or techniques elevating the lowered interstitial fluid pH. Intake of weak organic acids is found to improve the insulin resistance by elevating the lowered interstitial fluid pH in diabetes mellitus. One of the molecular mechanisms of the pH elevation is that: (1) the carboxyl group (R-COO−) but not H+ composing weak organic acids in foods is absorbed into the body, and (2) the absorbed the carboxyl group (R-COO−) behaves as a pH buffer material, elevating the interstitial fluid pH. On the other hand, high salt intake has been suggested to cause diabetes mellitus; however, the molecular mechanism is unclear. A possible mechanism of high salt intake-caused diabetes mellitus is proposed from a viewpoint of regulation of the interstitial fluid pH: high salt intake lowers the interstitial fluid pH via high production of H+ associated with ATP synthesis required for the Na+,K+-ATPase to extrude the high leveled intracellular Na+ caused by high salt intake. This review article introduces the molecular mechanism causing the lowered interstitial fluid pH and insulin resistance in diabetes mellitus, the improvement of insulin resistance via intake of weak organic acid-containing foods, and a proposal mechanism of high salt intake-caused diabetes mellitus.

scholarly journals Slowly Changing Bioelectric Potentials Associated With the Blood-Brain Barrier

1958 ◽  
Vol 195 (1) ◽  
pp. 7-22 ◽  
Author(s):  
Robert D. Tschirgi ◽  
J. Langdon Taylor
Keyword(s):  
Cerebral Cortex ◽  
Blood Brain Barrier ◽  
Interstitial Fluid ◽  
Brain Barrier ◽  
Membrane Diffusion ◽  
Arterial Blood ◽  
Blood Ph ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Bioelectric Potentials

A slowly changing bioelectric potential difference (P.D.) is measured in rats, rabbits, cats and dogs between various regions of the central nervous system (CNS) and the blood within the jugular vein. It is shown that the CNS-blood P.D. is very sensitive to alterations in alveolar CO2 tension, but this relationship is dependent upon the H+ concentration rather than CO2 per se. Whereas increasing intravenous H+ concentration increases CNS positivity, topical application of acid solutions directly to the cerebral cortex decreases CNS positivity. The same relationship is found for intravenous and topical K+. Anoxia and circulatory failure produce CNS negative deflections, often exceeding 15 mv, which do not return to zero for over 24 hours after death. Simultaneous measurements of arterial blood pH, cerebral cortex pH and CNS-blood P.D. reveal the following relationship among these variables: ΔP.D. = κ Δ log10 [H+]a/[H+]i where [H+]a is the H+ concentration of the arterial blood and [H+]i is the H+ concentration of the CNS interstitial fluid. For the CNS-blood P.D. between cerebral cortex and jugular blood of rabbits and rats, κ is found to be 29 ± 5. These results are interpreted as indicating a source of emf across the pan-vascular blood-brain barrier which resembles a membrane diffusion potential. The blood-brain barrier is postulated to be more permeable to H+ and K+ than to anions and other cations.

Leptin inhibits insulin binding in isolated rat adipocytes

1997 ◽  
Vol 155 (3) ◽  
pp. R5-R7 ◽  
Author(s):  
K Walder ◽  
A Filippis ◽  
S Clark ◽  
P Zimmet ◽  
GR Collier
Keyword(s):  
Insulin Resistance ◽  
Body Fat ◽  
Insulin Binding ◽  
The Body ◽  
Displacement Curve ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Binding Data ◽  
Isolated Adipocytes ◽  
Dose Dependent

Leptin is secreted from adipose tissue, and is thought to act as a 'lipostat', signalling the body fat levels to the hypothalamus resulting in adjustments to food intake and energy expenditure to maintain body weight homeostasis. In addition, plasma leptin concentrations have been shown to be related to insulin sensitivity independent of body fat content, suggesting that the hyperleptinemia found in obesity could contribute to the insulin resistance. We investigated the effects of leptin on insulin binding by isolated adipocytes. Adipocytes isolated from Sprague-Dawley rats exhibited a dose-dependent reduction in the uptake of 125I-labelled insulin when incubated with various concentrations of exogenous leptin. For example, addition of 50 nM leptin reduced total insulin binding in isolated adipocytes by 19% (P < 0.05). Analysis of displacement curve binding data suggested that leptin reduced maximal insulin binding in a dose-dependent manner, but had no significant effect on the affinity of insulin for its binding site. We conclude that leptin directly inhibited insulin binding by adipocytes, and the role of leptin in the development of insulin resistance in obese individuals requires further investigation.

Cerebral interstitial fluid acid-base status follows arterial acid-base perturbations

1982 ◽  
Vol 53 (6) ◽  
pp. 1551-1555 ◽  
Author(s):  
D. G. Davies ◽  
W. F. Nolan
Keyword(s):  
Cerebrospinal Fluid ◽  
New Zealand ◽  
Interstitial Fluid ◽  
Acid Base ◽  
Arterial Pco2 ◽  
Ph Probe ◽  
Arterial Blood ◽  
Blood Ph ◽  
New Zealand White Rabbits ◽  
Acid Base Status

Cerebral interstitial fluid (ISF) pH of ventral medulla or thalamus, cisternal cerebrospinal fluid (CSF) pH, and arterial blood pH, PCO2, and [HCO-3] were measured in chloralose-urethan-anesthetized, gallamine-paralyzed New Zealand White rabbits during 30-min episodes of either HCl or NaHCO3 intravenous infusions. ISF pH was measured continuously with glass microelectrodes (1- to 2-microns tip diameter). Cisternal CSF pH was measured continuously with an indwelling pH probe (1-mm tip diameter). Both ventral medullary and thalamic ISF [H+] changed significantly, whereas arterial PCO2 remained constant. CSF [H+] did not change. We conclude from these data that 1) changes in blood acid-base conditions are rapidly reflected in cerebral ISF and 2) transient differences in [H+] and [HCO-3] can exist between cerebral ISF and CSF.

The use of acidifying agents Aquasafe and Veleguard when rearing of broiler chickens

2020 ◽  
pp. 16-27
Author(s):  
L. Gamko ◽  
T. Tarinskaya
Keyword(s):  
Drinking Water ◽  
Organic Acids ◽  
Broiler Chickens ◽  
Positive Impact ◽  
The Body ◽  
Metabolic Energy ◽  
Control Group ◽  
Meat Production ◽  
Feed Conversion ◽  
Broiler Meat

It is known that necessary to replace the components of organic acids, which are part of acidifiers when drinking water to poultry in order to prevent the adaptation of microbes in the gastrointestinal tract. In the poultry industry organic acids are widely used, which are used as acidifiers to preserve the properties of water consumed. The purpose of this work was to evaluate the efficiency of broiler meat production when using acidifying agents of drinking water Aquasafe and Veleguard. The experimental part of the work has been performed in JSC “Kurinoe Tsarstvo-Bryansk” broiler area “Roshcha” in the Pochepsky district. The object of research was the livestock of broiler chickens cross Cobb 500 at floor housing. The effect of water acidifiers on meat productivity has been studied. Groups of chickens have been formed on the principle of pairs-analogues. Broiler chickens of experimental groups have been separated from the main livestock by a grid in the corner of the room for 100 heads in each group. It has been found by a result of research to be optimal dose usage of acidifying agents water Aquasafe and Veleguard to drink to broiler chickens. The positive effect of these acidifiers on the digestion of crude protein, crude fat, crude fiber, contributing to the effective use of nitrogen, which led to an increase in the intensity of growth, young animals’ livability and improved feed conversion. Slaughter yield in the control group was 55,1 %, and in the experimental group 57,2 and 58,4 %, which was by 2,1 and 3,3 % higher with the same level of metabolic energy and nutrients. In chickens that consumed acidifi ers more intensively used nutrients feed for deposition in the body of the components of the carcass, which affected the production. A positive impact of acidifying agents Aquasafe and Veleguard on meat quality in broiler chickens has been found.

scholarly journals Predictive Markers of Early Cardiovascular Impairment and Insulin Resistance in Obese Pediatric Patients

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 735
Author(s):  
Laura Mihaela Trandafir ◽  
Elena Cojocaru ◽  
Mihaela Moscalu ◽  
Maria Magdalena Leon Constantin ◽  
Ingrith Miron ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Plasma Cortisol ◽  
Predictive Power ◽  
Pediatric Patients ◽  
The Body ◽  
Control Group ◽  
Homa Index ◽  
Obese Patients ◽  
Metabolic Markers ◽  
Markers Of Inflammation

Background: The increased prevalence of obesity among children determined the rising number of its comorbidities in children and adults, too. This study aimed to evaluate certain markers of inflammation and insulin resistance in obese pediatric patients, identifying those who are more likely to develop further complications. Methods: We included 115 obese pediatric patients: 85 overweight and obese patients in the study group and 30 normal-weight patients in the control group. We calculated the body mass index (BMI) and we evaluated markers (biological, inflammatory) and the hormones profile. Results: Low-threshold inflammation was assessed by measuring interleukin 6 IL-6 and Intercellular Adhesion Molecules (ICAM). The analysis showed that IL-6 is significantly correlated with glucose (p = 0.001) and BMI value (p = 0.031). ICAM correlates significantly with triglycerides (p = 0.001), glucose (p = 0.044) and BMI percentile (p = 0.037). For pediatric obese patients, endotoxemia has been significantly correlated only with BMI percentile (p = 0.001). Plasma cortisol did not show significant correlations with total cholesterol, triglycerides, glucose or BMI percentile. The results indicated a significant predictive power of BMI percentile on inflammatory markers: IL-6 (AUC = 0.803, p < 0.001), ICAM (AUC = 0.806, p < 0.001) and endotoxemia (AUC = 0.762, p = 0.019). Additionally, BMI percentile has a significant predictive power for metabolic markers of insulin resistance (insulin value: AUC = 0.72, p < 0.001 and HOMA index: AUC = 0.68, p = 0.003). Conclusions: The study highlighted the importance of early markers of cardiovascular risk in obese pediatric patients represented by IL-6, ICAM, endotoxemia and their correlation with metabolic markers of insulin resistance represented by insulinemia, HOMA index and plasma cortisol. It can clearly be considered that the BMI percentile has significant predictive power for metabolic markers of insulin resistance.

scholarly journals On the Pathology of the dropsy produced by obstruction of the superior and inferior venœ and the portal vein.— Preliminary communication

1907 ◽  
Vol 79 (532) ◽  
pp. 267-283 ◽  
Keyword(s):  
Blood Pressure ◽  
Arterial Pressure ◽  
Portal Vein ◽  
Mean Arterial Blood Pressure ◽  
Normal Limit ◽  
The Body ◽  
Diastolic Filling ◽  
Arterial Blood ◽  
Preliminary Communication ◽  
The Mean

In August, 1903, I published a paper in the ‘Journal of Pathology’(1) in which I demonstrated a method experimentally producing uncompensated hear disease in an animal, which was compatible with life. This method consisted in diminishing the size of the pericardial sac by stitches, so that the diastolic filling of the heart was impeded. The main symptoms of this condition were dropsy and diminution in the amount of urine excreted. As the immediate result of this interference with the action of the heart, there occurred a rise of pressure throughout the whole systemic venous system extending as far back as the capillaries, and a fall of the mean arterial blood-pressure. Further, I found that the pressure in all the veins fell to the normal limit again within the space of about one hour, and that subsequently when dropsy was being produced, the vanous pressure in all parts of the body was normal, and the arterial pressure had almost recovered itself.

Seasonal changes in pancreatic B-cell function in euthermic yellow-bellied marmots

1985 ◽  
Vol 249 (2) ◽  
pp. R159-R165 ◽  
Author(s):  
G. L. Florant ◽  
A. K. Lawrence ◽  
K. Williams ◽  
W. A. Bauman
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
B Cell ◽  
Cell Function ◽  
Peripheral Resistance ◽  
The Body ◽  
Pancreatic B Cell ◽  
Peripheral Insulin Resistance ◽  
Body Weights ◽  
System Input

Fasting plasma insulin (PI) and glucose (PG) concentrations were measured throughout the body weight cycle of marmots. Animals gained weight during summer, and in late fall body weight peaked, after which they ceased feeding. Each month euthermic animals were injected intra-arterially with either dextrose (500 mg/kg) or porcine insulin (0.1 U/kg), and blood samples were collected over the subsequent 2 h. During weight gain fasting PI concentration and pancreatic B-cell response to injected dextrose increased markedly. Maximal insulin release to a dextrose challenge was measured during peak body weight or when body weight initially began to decline. The PG concentration after exogenous insulin administration was slight (less than 10%) in the fall but increased approximately 25% in the spring after marmots lost weight. Basal PG levels were not significantly different throughout the year. Basal fasting PI concentrations were significantly higher during the fall (P less than 0.01). It is suggested that in the fall, when marmots are obese, hyperinsulinemia and peripheral insulin resistance appear. Furthermore, in two animals with an increase in body weight of approximately 30% or less over the summer, peripheral resistance was demonstrable, albeit not as marked as in animals that appropriately doubled their body weights when given food ad libitum. Thus we hypothesize that factors other than adiposity, i.e., food intake, central nervous system input to the pancreatic B-cell, and/or changes in B-cell sensitivity to PG, may contribute to the observed peripheral insulin resistance and may be involved in body weight regulation.

Gelation of shark myofibrillar proteins by weak organic acids

1994 ◽  
Vol 50 (2) ◽  
pp. 185-190 ◽  
Author(s):  
V. Venugopal ◽  
S.N. Doke ◽  
P.M. Nair
Keyword(s):  
Organic Acids ◽  
Myofibrillar Proteins ◽  
Weak Organic Acids

Whole body insulin resistance in rat offspring of mothers consuming alcohol during pregnancy or lactation: comparing prenatal and postnatal exposure

2004 ◽  
Vol 96 (1) ◽  
pp. 167-172 ◽  
Author(s):  
Li Chen ◽  
B. L. Grégoire Nyomba
Keyword(s):  
Insulin Resistance ◽  
Birth Weight ◽  
Glucose Tolerance ◽  
The Body ◽  
Whole Body ◽  
Glucose Disposal ◽  
Tolerance Index ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Rat Offspring

This study examined the effects of maternal ethanol (EtOH) consumption during pregnancy or lactation on glucose homeostasis in the adult rat offspring. Glucose disposal was determined by minimal model during an intravenous glucose tolerance test in rats that had a small or normal birth weight after EtOH exposure in utero and in rats whose mothers were given EtOH during lactation only. All three EtOH groups had decreased glucose tolerance index and insulin sensitivity index, but their glucose effectiveness was not different from that of controls. In addition, EtOH rat offspring that were small at birth had elevated plasma, liver, and muscle triglyceride levels. The data show that EtOH exposure during pregnancy programs the body to insulin resistance later in life, regardless of birth weight, but that this effect also results in dyslipidemia in growth-restricted rats. In addition, insulin resistance is also evident after EtOH exposure during lactation.

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