Alcohol Intoxication and the Postburn Gastrointestinal Hormonal Response

Abstract Gastrointestinal hormones are essential in postburn metabolism. Since near 50% of burn victims test positive for blood alcohol levels at hospital admission and have inferior outcomes compared to nonintoxicated burn patients; we hypothesized that the gastrointestinal hormone secretion is compromised in intoxicated burn victims. To test our theory, we quantified gastrointestinal hormones serum levels in a combine ethanol intoxication and burn injury mouse model. Thus, mice received a daily dose of ethanol for 3 days, rested 4 days, and were given ethanol 3 additional days. Mice underwent 15% TBSA scald burn 30 minutes after their last ethanol dose. Serum samples were collected 24 hours after burn injury. Nonintoxicated burned mice exhibited an increase in glucose, insulin, ghrelin, plasminogen activator inhibitor-1, leptin, and resistin by 1.4-, 3-, 13.5-, 6.2-, 9.4-, and 2.4-fold, respectively, compared to sham vehicle mice (P < .05). Burn injury also reduced serum gastric inhibitory polypeptide (GIP) by 32% compared to sham-injured, vehicle-treated mice. Leptin, resistin, glucagon-like peptide-1, as well as insulin, were not different from sham groups when intoxication preceded burn injury. Nevertheless, in burned mice treated with ethanol, gastric inhibitory polypeptide and glucagon serum levels exhibited a significant fold increase of 3.5 and 4.7, respectively. With these results, we conclude that 24 hours after burn injury, mice developed significant changes in gastrointestinal hormones, along with hyperglycemia. Moreover, the combined insult of burn and ethanol intoxication led to additional hormonal changes that may be attributed to a potential pancreatic dysfunction. Further multiday studies are required to investigate the etiology, behavior, and clinical significance of these hormonal changes.

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Role of Bile Acids in the Regulation of Food Intake, and Their Dysregulation in Metabolic Disease

Nutrients ◽

10.3390/nu13041104 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1104

Author(s):

Cong Xie ◽

Weikun Huang ◽

Richard L. Young ◽

Karen L. Jones ◽

Michael Horowitz ◽

...

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Peptide Yy ◽

Glycogen Synthesis ◽

Hormone Secretion ◽

Gastrointestinal Hormones ◽

Farnesoid X Receptor ◽

Gastrointestinal Hormone ◽

Bile Acid Sequestrants

Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.

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The effect of sorbents on the serum levels of copper, iron and their transporting proteins at alcohol intoxication

Kazan medical journal ◽

10.17750/kmj2015-868 ◽

2015 ◽

Vol 96 (5) ◽

pp. 868-871

Author(s):

N A Terekhina ◽

E V Zhidko ◽

G A Terekhin ◽

A G Orbidans

Keyword(s):

Alcohol Abuse ◽

Membrane Permeability ◽

Erythrocyte Membrane ◽

Alcohol Intoxication ◽

Serum Levels ◽

Ethanol Intoxication ◽

Ceruloplasmin Level ◽

Acute Ethanol ◽

Acute Ethanol Intoxication ◽

Erythrocyte Membrane Permeability

Aim. Evaluate the effect of sorbents on erythrocyte membrane permeability and serum levels of copper, iron and their transporting proteins at acute ethanol intoxication. Methods. The study was performed on 94 rats. Acute alcohol intoxication was simulated on intact animals and in animals with prior artificial alcohol abuse. Acute ethanol intoxication was caused by intragastric administration of 40% ethanol at a dose of 0.5 of median lethal dose. Polysorb, Litovit, and Sapropel sorbents were administered at a dose of 3000 mg/kg 30 minutes after ethanol administration. permeability of erythrocyte membrane, serum levels of copper, iron, ceruloplasmin and transferrin were measured by spectrophotometry. Results. Levels of copper and iron in rat serum and erythrocyte membrane permeability significantly dropped compared to the control level at acute ethanol intoxication, ceruloplasmin level raised by 1.5 times, transferrin level did not change significantly. At acute ethanol intoxication in animals with prior artificial alcohol abuse, copper and iron levels and erythrocyte membrane permeability remained low, ceruloplasmin level remained high, transferrin level was decreased for 2 times. All sorbents were able to compensate the serum levels of copper, iron and ceruloplasmin in animals with prior artificial alcohol abuse, and Litovit and Polysorb also influenced on transferrin level. Conclusion. Compensatory effect of Polysorb, Litovit, and Sapropel on the serum levels of ceruloplasmin, copper, iron and transferrin and on erythrocyte membrane permeability was discovered at acute ethanol intoxication in animals with prior artificial alcohol abuse.

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Enteroendocrine Hormone Secretion and Metabolic Control: Importance of the Region of the Gut Stimulation

Pharmaceutics ◽

10.3390/pharmaceutics12090790 ◽

2020 ◽

Vol 12 (9) ◽

pp. 790 ◽

Cited By ~ 1

Author(s):

Cong Xie ◽

Karen L. Jones ◽

Christopher K. Rayner ◽

Tongzhi Wu

Keyword(s):

Gastric Emptying ◽

Hormone Secretion ◽

Gastrointestinal Hormones ◽

Postprandial Glucose ◽

Gastrointestinal Hormone ◽

Postprandial Metabolism ◽

Secretion Profile ◽

Meal Ingestion ◽

Small And Large Intestine

It is now widely appreciated that gastrointestinal function is central to the regulation of metabolic homeostasis. Following meal ingestion, the delivery of nutrients from the stomach into the small intestine (i.e., gastric emptying) is tightly controlled to optimise their subsequent digestion and absorption. The complex interaction of intraluminal nutrients (and other bioactive compounds, such as bile acids) with the small and large intestine induces the release of an array of gastrointestinal hormones from specialised enteroendocrine cells (EECs) distributed in various regions of the gut, which in turn to regulate gastric emptying, appetite and postprandial glucose metabolism. Stimulation of gastrointestinal hormone secretion, therefore, represents a promising strategy for the management of metabolic disorders, particularly obesity and type 2 diabetes mellitus (T2DM). That EECs are distributed distinctively between the proximal and distal gut suggests that the region of the gut exposed to intraluminal stimuli is of major relevance to the secretion profile of gastrointestinal hormones and associated metabolic responses. This review discusses the process of intestinal digestion and absorption and their impacts on the release of gastrointestinal hormones and the regulation of postprandial metabolism, with an emphasis on the differences between the proximal and distal gut, and implications for the management of obesity and T2DM.

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Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans: relationships with body mass index

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00134.2014 ◽

2014 ◽

Vol 307 (10) ◽

pp. G958-G967 ◽

Cited By ~ 27

Author(s):

Tanya J. Little ◽

Nicole J. Isaacs ◽

Richard L. Young ◽

Raffael Ott ◽

Nam Q. Nguyen ◽

...

Keyword(s):

Body Mass Index ◽

Cell Density ◽

Energy Intake ◽

Body Mass ◽

Hormone Secretion ◽

Gastrointestinal Hormones ◽

Inverse Correlation ◽

Duodenal Mucosa ◽

Gastrointestinal Hormone ◽

Glucagon Like Peptide 1

Fatty acids (FAs) stimulate the secretion of gastrointestinal hormones, including cholecystokinin (CCK) and glucagon like peptide-1 (GLP-1), which suppress energy intake. In obesity, gastrointestinal responses to FAs are attenuated. Recent studies have identified a key role for the FA-sensing receptors cluster of differentiation (CD)36, G protein-coupled receptor (GPR)40, GPR120, and GPR119 in mediating gastrointestinal hormone secretion. This study aimed to determine the expression and localization of these receptors in the duodenum of humans and to examine relationships with obesity. Duodenal mucosal biopsies were collected from nine lean [body mass index (BMI): 22 ± 1 kg/m2], six overweight (BMI: 28 ± 1 kg/m2), and seven obese (BMI: 49 ± 5 kg/m2) participants. Absolute levels of receptor transcripts were quantified using RT-PCR, while immunohistochemistry was used for localization. Transcripts were expressed in the duodenum of lean, overweight, and obese individuals with abundance of CD36>>GPR40>GPR120>GPR119. Expression levels of GPR120 ( r = 0.46, P = 0.03) and CD36 ( r = 0.69, P = 0.0004) were directly correlated with BMI. There was an inverse correlation between expression of GPR119 with BMI ( r2 = 0.26, P = 0.016). Immunolabeling studies localized CD36 to the brush border membrane of the duodenal mucosa and GPR40, GPR120, and GPR119 to enteroendocrine cells. The number of cells immunolabeled with CCK ( r = −0.54, P = 0.03) and GLP-1 ( r = −0.49, P = 0.045) was inversely correlated with BMI, such that duodenal CCK and GLP-1 cell density decreased with increasing BMI. In conclusion, CD36, GPR40, GPR120, and GPR119 are expressed in the human duodenum. Transcript levels of duodenal FA receptors and enteroendocrine cell density are altered with increasing BMI, suggesting that these changes may underlie decreased gastrointestinal hormone responses to fat and impaired energy intake regulation in obesity.

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Severity of thermal burn injury is associated with systemic neutrophil activation

10.1101/2021.10.07.21264679 ◽

2021 ◽

Author(s):

Maria Laggner ◽

Marie-Therse Lingitz ◽

Dragan Copic ◽

Martin Direder ◽

Katharina Klas ◽

...

Keyword(s):

Burn Injury ◽

Therapeutic Option ◽

Serum Levels ◽

Neutrophil Activation ◽

Burn Injuries ◽

Clinical Severity ◽

Complement Factor ◽

Post Injury ◽

Burn Victims ◽

Injury Progression

Objectives Burn injuries elicit a unique and dynamic stress response which can lead to burn injury progression. Though neutrophils represent crucial players in the burn-induced immunological events, the dynamic secretion pattern and systemic levels of neutrophil-derived factors have not been investigated in detail so far. Methods Serum levels of neutrophil elastase (NE), myeloperoxidase (MPO), citrullinated histone H3 (CitH3), and complement factor C3a were quantified in burn victims over 4 weeks post injury. Furthermore, the potential association with mortality, degree of burn injury, and inhalation trauma was evaluated. In addition, leukocyte, platelet, neutrophil, and lymphocyte counts were assessed. Lastly, we analyzed the association of neutrophil-derived factors with clinical severity scoring systems. Results Serum levels of NE, MPO, CitH3, and C3a were remarkably elevated in burn victims compared to healthy controls. Leukocyte and neutrophil counts were significantly increased on admission day and day 1, while relative lymphocytes were decreased in the first 7 days post burn trauma. Though neutrophil-derived factors did not predict mortality, patients suffering from 3rd degree burn injuries displayed increased CitH3 and NE levels. Accordingly, CitH3 and NE were elevated in cases with higher abbreviated burn severity indices (ABSI). Conclusions Taken together, our data suggest a role for neutrophil activation and NETosis in burn injuries and burn injury progression. Targeting exacerbated neutrophil activation might represent a new therapeutic option for severe cases of burn injury.

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Heavy Ethanol Intoxication Increases Proinflammatory Cytokines and Aggravates Hemorrhagic Shock-Induced Organ Damage in Rats

Mediators of Inflammation ◽

10.1155/2013/121786 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Tsung-Ming Hu ◽

Ru-Ping Lee ◽

Chung-Jen Lee ◽

Yi-Maun Subeq ◽

Nien-Tsung Lin ◽

...

Keyword(s):

Hemorrhagic Shock ◽

Alcohol Intoxication ◽

Lactic Dehydrogenase ◽

Serum Levels ◽

Organ Damage ◽

Ethanol Intoxication ◽

Total Blood ◽

Cytokine Levels ◽

Acute Ethanol ◽

Acute Ethanol Intoxication

Hemorrhagic shock (HS) following acute alcohol intoxication can increase proinflammatory cytokine production and induce marked immunosuppression. We investigated the effects of ethanol on physiopathology and cytokine levels following HS in acutely alcohol-intoxicated rats. Rats received an intravenous injection of 5 g/kg ethanol over 3 h followed by HS induced by withdrawal of 40% of total blood volume from a femoral arterial catheter over 30 min. Mean arterial pressure (MAP) and heart rate (HR) were monitored continuously for 48 h after the start of blood withdrawal. Biochemical parameters, including hemoglobin, ethanol, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), and creatine phosphokinase (CPK), were measured at 30 min before induction of HS and 0, 1, 3, 6, 9, 12, 18, 24, and 48 h after HS. Serum tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) levels were measured at 1 and 12 h after HS. The liver, kidneys, and lungs were removed for pathology at 48 h later. HS significantly increased HR, blood GOT, GPT, BUN, Cre, LDH, CPK, TNF-α, and IL-6 levels and decreased hemoglobin and MAP in rats. Acute ethanol intoxication further increased serum levels of GOT, GPT, BUN, Cre, LDH, CPK, TNF-αand IL-6 elevation following HS. Acutely intoxicated rats exacerbated the histopathologic changes in the liver, kidneys, and lungs following HS.

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Are the Changes in Gastrointestinal Hormone Secretion Necessary for the Success of Bariatric Surgery? A Critical Review of the Literature

Obesity Surgery ◽

10.1007/s11695-021-05568-7 ◽

2021 ◽

Author(s):

Charalampos Lampropoulos ◽

Theodoros Alexandrides ◽

Stylianos Tsochatzis ◽

Dimitrios Kehagias ◽

Ioannis Kehagias

Keyword(s):

Bariatric Surgery ◽

Critical Review ◽

Hormone Secretion ◽

Gastrointestinal Hormone ◽

Review Of The Literature

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Impact of Clomiphene Citrate on the Steroid Profile in Dysmetabolic Men with Low Testosterone Levels

Hormone and Metabolic Research ◽

10.1055/a-1542-8763 ◽

2021 ◽

Vol 53 (08) ◽

pp. 520-528

Author(s):

Carla Pelusi ◽

Flamina Fanelli ◽

Margherita Baccini ◽

Giovanni De Pergola ◽

Vincenzo Triggiani ◽

...

Keyword(s):

Clomiphene Citrate ◽

Serum Levels ◽

Male Hypogonadism ◽

Hormonal Changes ◽

Double Blind ◽

Adrenal Steroidogenesis ◽

Steroid Profiling ◽

Corticosteroid Binding Globulin ◽

Before And After ◽

17Β Estradiol

AbstractClomiphene citrate (CC) in male hypogonadism increases testosterone (T) and estrogen levels by stimulating pituitary gonadotropin release. Our group confirmed these hormonal changes in a randomized, cross-over, double-blind trial of CC versus placebo in addition to metformin, conducted in 21 obese dysmetabolic men with low T levels. However, we hypothesize that based on its mechanism of action, CC may directly or indirectly affect adrenal steroidogenesis. The aim of this sub-study was to better understand the changes in steroid levels and metabolism induced by CC treatment. We assessed 17α-hydroxypregnelone (17αOH-P5), dehydroepiandrosterone (DHEA), progesterone (P4), 17α-hydroxyprogesterone (17αOH-P4), androstenedione (A), T, dihydrotestosterone (DHT), estrone (E1), 17β-estradiol (E2), 11-deoxycortisol (11 S), cortisol (F), and cortisone (E) by LC-MS/MS, and corticosteroid binding globulin (CBG) by ELISA, before and after each treatment. In addition, free-F and steroid product/precursor ratios were calculated. We observed a significant change in serum levels induced by CC compared with placebo for 17αOH-P4, DHT, T, E2, E1, F, E, and CBG, but not free-F. In addition, compared to placebo, CC induced higher 17αOH-P4/P4, E2/E1, 17αOH-P4/17αOH-P5, A/17αOH-P4, T/A, E1/A, F/11 S, and F/E ratios. Therefore, besides the CC stimulating effect on testis steroidogenesis, our study showed increased F, E, but not free-F, levels, indicating changes in steroid metabolism rather than adrenal secretion stimulation. The steroid profiling also revealed the CC stimulation of the Δ5 rather than the Δ4 pathway, thus indicating considerable testicular involvement in the increased androgen secretion.

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D-thyroxine reduces lipoprotein(a) serum concentration in dialysis patients.

Journal of the American Society of Nephrology ◽

10.1681/asn.v9190 ◽

1998 ◽

Vol 9 (1) ◽

pp. 90-96

Author(s):

C Bommer ◽

E Werle ◽

I Walter-Sack ◽

C Keller ◽

F Gehlen ◽

...

Keyword(s):

Serum Concentration ◽

Ldl Cholesterol ◽

Clinical Symptoms ◽

Hormone Secretion ◽

Elevated Serum ◽

Serum Levels ◽

Controlled Study ◽

Dialysis Patients ◽

Lipoprotein A ◽

Thyroxine Therapy

Uremia raises lipoprotein(a) (Lp(a)) serum concentration and the risk of arteriosclerosis in dialysis patients. The treatment of high Lp(a) levels is not satisfactory today. The decrease of Lp(a) in hypothyroid patients on L-T4 therapy raised the question of whether dextro-thyroxine (D-thyroxine) reduces not only serum cholesterol, but also Lp(a) serum concentration. In a single-blind placebo-controlled study, the influence of D-thyroxine therapy on Lp(a) serum concentration was evaluated in 30 hemodialysis patients with elevated Lp(a) serum levels. Lp(a) was quantified in parallel by two methods, i.e., rocket immunoelectrophoresis and nephelometry, and apo(a) isoforms were determined by a sensitive immunoblotting technique. Regardless of the apo(a) isoforms, 6 mg/d D-thyroxine reduced elevated Lp(a) levels significantly by 27 +/- 13% in 20 dialysis patients (P < 0.001) compared with 10 control subjects (-9.9 +/- 8.4%). In parallel, D-thyroxine therapy significantly lowered total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), and LDL cholesterol/HDL cholesterol ratio (P < 0.01); raised T4 and T3 serum levels; and suppressed thyroid-stimulating hormone secretion without causing clinical symptoms of hyperthyroidism in any of the patients. D-Thyroxine reduces elevated serum Lp(a) concentration in dialysis patients. The effect in nondialysis patients can be expected but remains to be proven.

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