The role of liver in metabolism: an updated review with physiological emphasis

Liver plays an essential role in metabolism and has an important role in preserving and regulating the levels of lipid, glucose in the body as well as energy metabolism. Among the important functions performed by the liver is maintaining of blood glucose levels under different conditions through group of processes included; glycolysis, glycogenesis, glycogenolysis, gluconeogenesis. The absorbed free fatty acids and those derived from the adipose tissue reach the liver and are utilized for energy, membrane synthesis, or stored as triglyceride. In addition, the liver has a crucial role in keeping homeostasis of body level of cholesterol. Regarding protein metabolism, urea cycle occurs in the liver through the action of urea cycle enzymes to produce urea in order to get rid of the toxic ammonia. In the liver, cholesterol is utilized for bile acids synthesis through a complicated process. These bile acids are considered essential in order to absorb and transport of lipid-soluble vitamins dietary and fat in the diet as well as clearance of drugs, toxic substances and xenobiotics. Adding to these hepatic functions is hepatic detoxification where liver metabolizes a various type of drugs to make soluble execretable compounds. In conclusion, the liver has so important metabolic functions which if impaired will resulted in many liver diseases and might progress to more dangerous conditions such as liver fibrosis or cirrhosis.

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HOMEOSTASIS OF CHOLESTEROL IN THE BODY, MECHANISMS OF ITS DISORDER, ROLE OF 7α-HYDROXYLASE

Likarska sprava ◽

10.31640/jvd.1-2.2021(4) ◽

2021 ◽

pp. 19-31

Author(s):

V. K. Kazymyrko ◽

T. S. Silantieva ◽

A. G. Dubkova ◽

L. N. Ivanitska ◽

V. V. Kutovyi

Keyword(s):

Bile Acids ◽

Unsaturated Fatty Acids ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Point Of View ◽

The Body ◽

Cholesterol Homeostasis ◽

Liver Cholesterol ◽

Positive Balance

It has been shown that in humans and animals, CS homeostasis occurs in accordance with the same formula: (СSendog + CSexog) – (CSexcr + BAexcr) = 0. But in herbivores, the positive balance of CS in the body is not occurs; a person creates it by consuming animal products, high-calorie foods and substrates for the synthesis of cholesterol. Like herbivores, it does not need constant intake of cholesterol from the food, the release of which from the body in the form of bile acids is also limited by 7α-hydroxylase activity. This point of view is supported by the fact that a person's daily need for cholesterol can be met by one of its biosynthesis. The paper provides information on the role of liver cholesterol homeostasis and the transformation of cholesterol into bile acids (BA) in the disturbance of homeostasis. Hydroxylation is the only process that irreversibly removes CS from membranes and LP-complexes. For the formation of BA, 60–80 % of the total cholesterol synthesized daily in the body is spent. The rate of the 7α-hydroxylase reaction is affected by the presence of hypercholesterolemia: in experimental animals and in patients with HCS, the rate of the 7α-hydroxylase reaction of the liver is sharply reduced, the rate of conversion of cholesterol to BA and its removal from the body is reduced. A role in atherogenesis of a decrease in the rate of 7α-hydroxylation with aging in humans has been shown. The fact is underlined that the release of cholesterol in the form of bile acids reflects the rate of its synthesis in the body. The formation of BA and the excretion of cholesterol is inhibited by insufficient intake of vitamin C and unsaturated fatty acids into the human body. It is concluded that it is necessary to search for and synthesize substances that enhance the conversion of cholesterol into bile acids and its excretion from the body. The combination of stimulators of bile acid synthesis and blockers of HMG-CoA reductase can significantly increase the effectiveness of treatment of patients with atherosclerosis.

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Role of Insulin in Health and Disease: An Update

International Journal of Molecular Sciences ◽

10.3390/ijms22126403 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6403

Author(s):

Md Saidur Rahman ◽

Khandkar Shaharina Hossain ◽

Sharnali Das ◽

Sushmita Kundu ◽

Elikanah Olusayo Adegoke ◽

...

Keyword(s):

Insulin Signaling ◽

Basic Research ◽

Future Research ◽

Protective Effects ◽

Glucose Levels ◽

Physiological Processes ◽

Blood Glucose Levels ◽

Wide Range ◽

Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

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Role of Melanocortin Signaling in Neuroendocrine and Metabolic Actions of Leptin in Male Rats With Uncontrolled Diabetes

Endocrinology ◽

10.1210/en.2014-1169 ◽

2014 ◽

Vol 155 (11) ◽

pp. 4157-4167 ◽

Cited By ~ 16

Author(s):

Thomas H. Meek ◽

Miles E. Matsen ◽

Vincent Damian ◽

Alex Cubelo ◽

Streamson C. Chua ◽

...

Keyword(s):

Male Rats ◽

Melanocortin Receptor ◽

Glucose Lowering ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Uncontrolled Diabetes ◽

Streptozotocin Induced Diabetes ◽

Melanocortin Signaling ◽

Antidiabetic Effects

Abstract Although the antidiabetic effects of leptin require intact neuronal melanocortin signaling in rodents with uncontrolled diabetes (uDM), increased melanocortin signaling is not sufficient to mimic leptin's glucose-lowering effects. The current studies were undertaken to clarify the role of melanocortin signaling in leptin's ability to correct metabolic and neuroendocrine disturbances associated with uDM. To accomplish this, bilateral cannulae were implanted in the lateral ventricle of rats with streptozotocin-induced diabetes, and leptin was coinfused with varying doses of the melanocortin 3/4 receptor (MC3/4R) antagonist, SHU9119. An additional cohort of streptozotocin-induced diabetes rats received intracerebroventricular administration of either the MC3/4R agonist, melanotan-II, or its vehicle. Consistent with previous findings, leptin's glucose-lowering effects were blocked by intracerebroventricular SHU9119. In contrast, leptin-mediated suppression of hyperglucagonemia involves both melanocortin dependent and independent mechanisms, and the degree of glucagon inhibition was associated with reduced plasma ketone body levels. Increased central nervous system melanocortin signaling alone fails to mimic leptin's ability to correct any of the metabolic or neuroendocrine disturbances associated with uDM. Moreover, the inability of increased melanocortin signaling to lower diabetic hyperglycemia does not appear to be secondary to release of the endogenous MC3/4R inverse agonist, Agouti-related peptide (AgRP), because AgRP knockout mice did not show increased susceptibility to the antidiabetic effects of increased MC3/4R signaling. Overall, these data suggest that 1) AgRP is not a major driver of diabetic hyperglycemia, 2) mechanisms independent of melanocortin signaling contribute to leptin's antidiabetic effects, and 3) melanocortin receptor blockade dissociates leptin's glucose-lowering effect from its action on other features of uDM, including reversal of hyperglucagonemia and ketosis, suggesting that brain control of ketosis, but not blood glucose levels, is glucagon dependent.

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Non-Invasive Determination of Blood Glucose Levels by Optical Waveguide

Iranian journal of diabetes and obesity ◽

10.18502/ijdo.v13i4.8001 ◽

2021 ◽

Author(s):

Mohsen Askarbioki ◽

Mojtaba Mortazavi ◽

Abdolhamid Amooee ◽

Saeid Kargar ◽

Mohammad Afkhami-Ardekani ◽

...

Keyword(s):

Blood Glucose ◽

Optical Waveguide ◽

Interstitial Fluid ◽

Evanescent Waves ◽

The Body ◽

Statistical Population ◽

Glucose Levels ◽

Non Invasive ◽

Blood Glucose Levels

Objective: Today, there are various non-invasive techniques available for the determination of blood glucose levels. In this study, the level of blood glucose was determined by developing a new device using near-infrared (NIR) wavelength, glass optical waveguide, and the phenomenon of evanescent waves. Materials and Methods: The body's interstitial fluid has made possible the development of new technology to measure the blood glucose. As a result of contacting the fingertip with the body of the borehole rod, where electromagnetic waves are reflected inside, evanescent waves penetrate from the borehole into the skin and are absorbed by the interstitial fluid. The electromagnetic wave rate absorption at the end of the borehole rod is investigated using a detection photodetector, and its relationship to the people's actual blood glucose level. Following precise optimization and design of the glucose monitoring device, a statistical population of 100 participants with a maximum blood glucose concentration of 200 mg/dL was chosen. Before measurements, participants put their index finger for 30 seconds on the device. Results: According to this experimental study, the values measured by the innovative device with Clark grid analysis were clinically acceptable in scales A and B. The Adjusted Coefficient of Determination of the data was estimated to be 0.9064. Conclusion: For future investigations, researchers are recommended to work with a larger statistical population and use error reduction trends to improve the accuracy and expand the range of measurements.

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Prediabetes, undiagnosed diabetes and diabetes risk in Italy in 2017–2018: results from the first National screening campaign in community pharmacies

Journal of Public Health ◽

10.1093/pubmed/fdab046 ◽

2021 ◽

Author(s):

P Brunetti ◽

L Baldessin ◽

S Pagliacci

Keyword(s):

High Risk ◽

Diabetes Risk ◽

World Health ◽

Undiagnosed Diabetes ◽

Community Pharmacies ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Health Organization ◽

Very High

Abstract Background Effective policies for diabetes prevention remain urgent. We conducted a mass screening campaign in Italy to identify subjects potentially having undiagnosed diabetes, prediabetes or at diabetes risk. Methods This cohort study was conducted in community pharmacies joining the unitary National federation of pharmacy holders (Federfarma) and participating in the 7-day screening campaign ‘DiaDay’ in 2017–2018. Capillary blood glucose levels and the risk of developing diabetes in 10 years (through the Finnish Diabetes Risk Score) were assessed. Results 145 651 volunteers aged ≥20 years without known diabetes were screened at 5671 community pharmacies in 2017 and 116 097 at 5112 in 2018. Overall, 3.6% had glucose values suggestive of undiagnosed diabetes; under fasting conditions (N = 94 076), 39.9% and 16.4% had values suggestive of prediabetes by the American Diabetes Association and the World Health Organization criteria, respectively. Of those without diabetes (N = 252 440), 19.2% had scores compatible with a high risk (1:3) and 2.7% with a very high risk (1:2) of developing the disease; in the prediabetes group, the risk rose with higher impaired fasting glucose values. Conclusions DiaDay, the first National screening campaign, highlights the need to screen the population and the key role of the pharmacist both in screening activities and education promotion.

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Dynamic Rule-Based Algorithm to Tune Insulin-on-Board Constraints for a Hybrid Artificial Pancreas System

Journal of Healthcare Engineering ◽

10.1155/2020/1414597 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Arthur Bertachi ◽

Lyvia Biagi ◽

Aleix Beneyto ◽

Josep Vehí

Keyword(s):

Type 1 Diabetes ◽

Insulin Infusion ◽

Artificial Pancreas ◽

The Body ◽

Control Algorithms ◽

Rule Based ◽

Control Blood Glucose ◽

Glucose Levels ◽

Blood Glucose Levels

The artificial pancreas (AP) is a system intended to control blood glucose levels through automated insulin infusion, reducing the burden of subjects with type 1 diabetes to manage their condition. To increase patients’ safety, some systems limit the allowed amount of insulin active in the body, known as insulin-on-board (IOB). The safety auxiliary feedback element (SAFE) layer has been designed previously to avoid overreaction of the controller and thus avoiding hypoglycemia. In this work, a new method, so-called “dynamic rule-based algorithm,” is presented in order to adjust the limits of IOB in real time. The algorithm is an extension of a previously designed method which aimed to adjust the limits of IOB for a meal with 60 grams of carbohydrates (CHO). The proposed method is intended to be applied on hybrid AP systems during 24 h operation. It has been designed by combining two different strategies to set IOB limits for different situations: (1) fasting periods and (2) postprandial periods, regardless of the size of the meal. The UVa/Padova simulator is considered to assess the performance of the method, considering challenging scenarios. In silico results showed that the method is able to reduce the time spent in hypoglycemic range, improving patients’ safety, which reveals the feasibility of the approach to be included in different control algorithms.

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The Role of Biomaterials in Insulin Delivery Systems

The International Journal of Artificial Organs ◽

10.1177/039139888000300513 ◽

1980 ◽

Vol 3 (5) ◽

pp. 299-304 ◽

Cited By ~ 1

Author(s):

S.D. Bruck

Keyword(s):

Blood Glucose ◽

Glucose Sensor ◽

Insulin Delivery ◽

The United States ◽

Delivery Systems ◽

Open Loop ◽

Health Concern ◽

Glucose Levels ◽

Blood Glucose Levels

The control of blood glucose levels in diabetes involving devices are critically reviewed, and the role of blood-contacting biomaterial components analyzed. These include mechanical insulin-delivery systems of the closed-loop type that require an electronic glucose sensor and feedback, and open-loop systems that deliver insulin without a sensor and feedback. Whole pancreatic and islet transplantations, islet encapsulation, and the potential role of polymeric sustained drug delivery systems are discussed. The medical and social impacts of diabetes mellitus are of prime public health concern and of even greater magnitude than those of heart disease in the United States. While future advances in device design, miniaturization, and biometrials technology will significantly add to the arsenal of therapeutic alternatives, devices capable of controlling blood glucose levels ought to be viewed as mere interim phases rather than as final goals of the problem.

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Liver glycogen content decreases during meals in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1982.243.3.r450 ◽

1982 ◽

Vol 243 (3) ◽

pp. R450-R453

Author(s):

W. Langhans ◽

N. Geary ◽

E. Scharrer

Keyword(s):

Blood Glucose ◽

Glycogen Content ◽

Liver Glycogen ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Liver Glycogen Content ◽

Ad Libitum ◽

Portal Veins ◽

Hepatic Portal

The effects of feeding on liver glycogen content and blood glucose in the hepatic and hepatic portal veins were investigated in rats. Liver glycogen content decreased about 25% during meals both in rats refed after 12 h food deprivation (23 +/- 1 to 17 +/- 1 mg glycogen/g liver) and in ad libitum-fed rats taking fully spontaneous meals (44 +/- 2 to 32 +/- 2 mg/g). Liver glycogen began to increase within 30 min after meals in ad libitum-fed rats. Hepatic vein blood glucose levels at meal onset (118 +/- 4 mg/dl in the food-deprived rats, 127 +/- 4 in ad libitum-fed rats) and at meal end (155 +/- 3 and 166 +/- 5 mg/dl, respectively) were similar in the two groups. Portal vein blood glucose increased during meals in the previously food-deprived rats (83 +/- 4 to 116 +/- 6 mg/dl) but not in the ad libitum-fed rats (127 +/- 5 to 132 +/- 3 mg/dl). Mechanisms that may elicit prandial glycogenolysis and the possible role of this effect in the production of meal ending satiety are discussed.

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Decreased Skin-Mediated Detoxification Contributes to Oxidative Stress and Insulin Resistance

Experimental Diabetes Research ◽

10.1155/2012/128694 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9

Author(s):

Xing-Xing Liu ◽

Chang-Bin Sun ◽

Ting-Tong Yang ◽

Da Li ◽

Chun-Yan Li ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Toxic Substances ◽

Insulin Levels ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Glucose Injection ◽

Plasma Insulin Levels ◽

Induced Changes ◽

The Relationship

The skin, the body's largest organ, plays an important role in the biotransformation/detoxification and elimination of xenobiotics and endogenous toxic substances, but its role in oxidative stress and insulin resistance is unclear. We investigated the relationship between skin detoxification and oxidative stress/insulin resistance by examining burn-induced changes in nicotinamide degradation. Rats were divided into four groups: sham-operated, sham-nicotinamide, burn, and burn-nicotinamide. Rats received an intraperitoneal glucose injection (2 g/kg) with (sham-nicotinamide and burn-nicotinamide groups) or without (sham-operated and burn groups) coadministration of nicotinamide (100 mg/kg). The results showed that the mRNA of all detoxification-related enzymes tested was detected in sham-operated skin but not in burned skin. The clearance of nicotinamide andN1-methylnicotinamide in burned rats was significantly decreased compared with that in sham-operated rats. After glucose loading, burn group showed significantly higher plasma insulin levels with a lower muscle glycogen level than that of sham-operated and sham-nicotinamide groups, although there were no significant differences in blood glucose levels over time between groups. More profound changes in plasma H2O2and insulin levels were observed in burn-nicotinamide group. It may be concluded that decreased skin detoxification may increase the risk for oxidative stress and insulin resistance.

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Assessment of Blood Glucose and Electrolytes during Cardiopulmonary Bypass in Diabetic and Non-Diabetic Patients of Pakistan

Global Journal of Health Science ◽

10.5539/gjhs.v8n9p159 ◽

2016 ◽

Vol 8 (9) ◽

pp. 159

Author(s):

Muhammad Bilal ◽

Abdul Haseeb ◽

Mohammad Hassaan Khan ◽

Akash Khetpal ◽

Muhammad Saad ◽

...

Keyword(s):

Blood Glucose ◽

Cardiopulmonary Bypass ◽

Repeated Measures ◽

Artery Bypass ◽

The Body ◽

Diabetic Patients ◽

Blood Electrolytes ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Significant Difference

INTRODUCTION: Perioperative hyperglycemia has been shown to be related to higher levels of morbidity and mortality in patients on cardiopulmonary bypass (CPB) undergoing coronary artery bypass grafting (CABG), both diabetic and non-diabetic. Blood electrolytes, like sodium, potassium, calcium, and chloride play a very important role in the normal functioning of the body and can lead to a variety of clinical disorders if they become deficient. A minimal number of studies have been conducted on the simultaneous perioperative changes in both blood glucose and electrolyte levels during CPB in Pakistan. Therefore, our aim is to record and compare the changes in blood glucose and electrolyte levels during CPB in diabetic and non-diabetic patients.MATERIALS & METHODS: This was a prospective, observational study conducted on 200 patients who underwent CABG with CPB, from October 2014 to March 2015. The patients were recruited from the Cardiac Surgery Ward, Civil Hospital Karachi after they complied with the inclusion criteria. Repeated-measures analysis of variance (ANOVA) was used to compare the trend of the changes perioperatively for the two groups.RESULTS: There was no significant difference in changes in blood glucose between the two groups (P = 0.62). The only significant difference detected between the two groups was for PaCO2 (P = 0.001). Besides, further analysis revealed insignificant group differences for the trend changes in other blood electrolytes (P > 0.05).CONCLUSION: Our findings highlighted that there is no significant difference in blood electrolytes changes and the increase in blood glucose levels between diabetic and non-diabetic patients.

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