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1. A multi-society Delphi consensus statement on new fatty liver disease nomenclature

Author

Mary E, R, Jeffrey V, L, Vlad, R, Sven M, F, Arun J, S, Fasiha, K, Diana, R, Manal F, A, Quentin M, A, Juan Pablo, A, Marco, A, Ramon, B, Ulrich, B, Jerome, B, Elisabetta, B, Christopher, B, Graciela E, C, Abhijit, C, Helena, C, Donna, C, Kenneth, C, Mohamed, E, Samuel, K, Wayne, E, Jiangao, F, Samer, G, Cynthia D, G, Stephen A, H, Seung Up, K, Bart, K, Marko, K, Kris, K, Florence, L, Rohit, L, Robert, M, Timothy R, M, Elisabeth, P, Michael, R, Manuel, R, Marcelo, S, Shivaram Prasad, S, Silvia C, S, C Wendy, S, Dina, T, Luca, V, Miriam B, V, Vincent, W, Stavra, X, Yusuf, Y, Zobair, Y, Ansley, H, Marcela, V, Newsome, NVeeral Ajmeral, P, Alazawi, W, Alkhatry, M, Alkhouri, N, Allen, A, Allison, M, Alswat, K, R Alvares-da-Silva, M, Alves-Bezerra, M, J Armstrong, M, Arufe, D, Aschner, P, Baffy, G, Bansal, M, Bedossa, P, Belfort, R, Berg, T, Berzigotti, A, Betel, M, Bianco, C, Brass, C, L Brosgart, C, Matthews Brunt, E, Buti, M, Caldwell, S, Carr, R, Casanovas, T, Castera, L, Caussy, C, Cerda, E, Chalasani, N, Kheong Chan, W, Charatcharoenwitthaya, P, Charlton, M, Cheung, A, Chiodi, D, Chung, R, Cohen, D, Corey, K, P Cotrim, H, Crespo, J, Dassanayake, A, Davidson, N, De Knegt, R, De Ledinghen, V, Demir, M, Diaz, S, Mae Diehl, A, Dimmig, B, Dirchwolf, M, Duseja, A, Dvorak, K, Ekstedt, M, El Wakil, R, Lucía Ferraz, M, Friedman, S, Fuchs, M, Gastaldelli, A, Geerts, A, Geier, A, Girala, M, Goh, G, Goossens, N, Graupera, I, Hagström, H, Henry, Z, Hunyady, B, Hutchison, A, Isaacs, S, Jornayvaz, F, Kemp, C, Kile, D, Kim, W, Kleiner, D, Kohli, R, Kugelmas, M, Lavine, J, Lazo, M, Leite, N, Lozano, A, Luukkonen, P, Macedo, P, Mansour, D, Mantzoros, C, Marchesini, G, Marciano, S, Martinez, K, Vladimirova Mateva, L, M Mato, J, Mccary, A, Miele, L, Mikolasevic, I, Miller, V, Moreno, R, Moylan, C, Nakajima, A, Charles Nault, J, Norris, S, Noureddin, M, P Oliveira, C, Ong, A, Padilla, M, Pais, R, Panduro, A, K Panigrahi, M, Papatheodoridis, G, Pelusi, S, Pérez, M, Perez Escobar, J, Perseghin, G, Pessoa, M, Petta, S, Pinzani, M, Platon Lupsor, M, Rabiee, A, Romeo, S, Rotman, Y, Rowe, I, Salupere, R, Satapathy, S, M Schattenberg, J, Schaufert, W, Schnabl, B, Seim, L, Serfaty, L, Shapiro, D, K Singal, A, Skladany, L, Stefan, N, Stine, J, Sundaram, S, Svegliati-Baroni, G, Szabo, G, Tacke, F, Tanwandee, T, Targher, G, Terrault, N, Tetri, B, Thiele, M, Tisthammer, B, Torre Delgadillo, A, Trauner, M, Tsochatzis, E, Van Kleef, L, Van Mil, S, Vanwagner, L, Antonio Velarde Ruiz Velasco, J, Vesterhus, M, Vilar-Gomez, E, Watt, K, Wattacheril, J, Wilkins, F, Willemse, J, Zekry, A, Zelber-Sagi, S, Rinella, Mary E, Lazarus, Jeffrey V, Ratziu, Vlad, Francque, Sven M, Sanyal, Arun J, Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F, Anstee, Quentin M, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher, Castro Narro, Graciela E, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna, Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D, Harrison, Stephen A, Kim, Seung Up, Koot, Bart, Korenjak, Marko, Kowdley, Kris, Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R, Powell, Elisabeth, Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C, Spearman, C Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B, Wai-Sun Wong, Vincent, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Philip NVeeral Ajmeral, William Alazawi, Maryam Alkhatry, Naim Alkhouri, Alina Allen, Michael Allison, Khalid Alswat, Mario R Alvares-da-Silva, Michele Alves-Bezerra, Matthew J Armstrong, Diego Arufe, Pablo Aschner, Gyorgy Baffy, Meena Bansal, Pierre Bedossa, Renata Belfort, Thomas Berg, Annalisa Berzigotti, Michael Betel, Cristiana Bianco, Clifford Brass, Carol L Brosgart, Elizabeth Matthews Brunt, Maria Buti, Steve Caldwell, Rotonya Carr, Teresa Casanovas, Laurent Castera, Cyrielle Caussy, Eira Cerda, Naga Chalasani, Wah Kheong Chan, Phunchai Charatcharoenwitthaya, Michael Charlton, Amanda Cheung, Daniela Chiodi, Ray Chung, David Cohen, Kathleen Corey, Helma P Cotrim, Javier Crespo, Anuradha Dassanayake, Nicholas Davidson, Robert De Knegt, Victor De Ledinghen, Münevver Demir, Sebastian Diaz, Anna Mae Diehl, Bruce Dimmig, Melisa Dirchwolf, Ajay Duseja, Karel Dvorak, Mattias Ekstedt, Reda El Wakil, María Lucía Ferraz, Scott Friedman, Michael Fuchs, Amalia Gastaldelli, Anja Geerts, Andreas Geier, Marcos Girala, George Goh, Nicolas Goossens, Isabel Graupera, Hannes Hagström, Zachary Henry, Bela Hunyady, Alan Hutchison, Scott Isaacs, François Jornayvaz, Cynthia Kemp, Denise Kile, Won Kim, David Kleiner, Rohit Kohli, Marcelo Kugelmas, Joel Lavine, Mariana Lazo, Nathalie Leite, Adelina Lozano, Panu Luukkonen, Paula Macedo, Dina Mansour, Christos Mantzoros, Giulio Marchesini, Sebastián Marciano, Kim Martinez, Lyudmila Vladimirova Mateva, Jose M Mato, Alexis McCary, Luca Miele, Ivana Mikolasevic, Veronica Miller, Rosalba Moreno, Cynthia Moylan, Atsushi Nakajima, Jean Charles Nault, Suzanne Norris, Mazen Noureddin, C P Oliveira, Arlin Ong, Martín Padilla, Raluca Pais, Arturo Panduro, Manas K Panigrahi, George Papatheodoridis, Serena Pelusi, Marlene Pérez, Juanita Perez Escobar, Gianluca Perseghin, Mario Pessoa, Salvatore Petta, Massimo Pinzani, Monica Platon Lupsor, Atoosa Rabiee, Stefano Romeo, Yaron Rotman, Ian Rowe, Riina Salupere, Sanjaya Satapathy, Jörn M Schattenberg, Wendy Schaufert, Bernd Schnabl, Lynn Seim, Lawrence Serfaty, David Shapiro, Ashwani K Singal, Lubomir Skladany, Norbert Stefan, Jonathan Stine, Shikha Sundaram, Gianluca Svegliati-Baroni, Gyonzgi Szabo, Frank Tacke, Tawesak Tanwandee, Giovanni Targher, Norah Terrault, Brent Tetri, Maja Thiele, Baron Tisthammer, Aldo Torre Delgadillo, Michael Trauner, Emmanuel Tsochatzis, Laurens Van Kleef, Saskia Van Mil, Lisa VanWagner, Jose Antonio Velarde Ruiz Velasco, Mette Vesterhus, Eduardo Vilar-Gomez, Kymberly Watt, Julia Wattacheril, Fonda Wilkins, José Willemse, Amany Zekry, Shira Zelber-Sagi, Mary E, R, Jeffrey V, L, Vlad, R, Sven M, F, Arun J, S, Fasiha, K, Diana, R, Manal F, A, Quentin M, A, Juan Pablo, A, Marco, A, Ramon, B, Ulrich, B, Jerome, B, Elisabetta, B, Christopher, B, Graciela E, C, Abhijit, C, Helena, C, Donna, C, Kenneth, C, Mohamed, E, Samuel, K, Wayne, E, Jiangao, F, Samer, G, Cynthia D, G, Stephen A, H, Seung Up, K, Bart, K, Marko, K, Kris, K, Florence, L, Rohit, L, Robert, M, Timothy R, M, Elisabeth, P, Michael, R, Manuel, R, Marcelo, S, Shivaram Prasad, S, Silvia C, S, C Wendy, S, Dina, T, Luca, V, Miriam B, V, Vincent, W, Stavra, X, Yusuf, Y, Zobair, Y, Ansley, H, Marcela, V, Newsome, NVeeral Ajmeral, P, Alazawi, W, Alkhatry, M, Alkhouri, N, Allen, A, Allison, M, Alswat, K, R Alvares-da-Silva, M, Alves-Bezerra, M, J Armstrong, M, Arufe, D, Aschner, P, Baffy, G, Bansal, M, Bedossa, P, Belfort, R, Berg, T, Berzigotti, A, Betel, M, Bianco, C, Brass, C, L Brosgart, C, Matthews Brunt, E, Buti, M, Caldwell, S, Carr, R, Casanovas, T, Castera, L, Caussy, C, Cerda, E, Chalasani, N, Kheong Chan, W, Charatcharoenwitthaya, P, Charlton, M, Cheung, A, Chiodi, D, Chung, R, Cohen, D, Corey, K, P Cotrim, H, Crespo, J, Dassanayake, A, Davidson, N, De Knegt, R, De Ledinghen, V, Demir, M, Diaz, S, Mae Diehl, A, Dimmig, B, Dirchwolf, M, Duseja, A, Dvorak, K, Ekstedt, M, El Wakil, R, Lucía Ferraz, M, Friedman, S, Fuchs, M, Gastaldelli, A, Geerts, A, Geier, A, Girala, M, Goh, G, Goossens, N, Graupera, I, Hagström, H, Henry, Z, Hunyady, B, Hutchison, A, Isaacs, S, Jornayvaz, F, Kemp, C, Kile, D, Kim, W, Kleiner, D, Kohli, R, Kugelmas, M, Lavine, J, Lazo, M, Leite, N, Lozano, A, Luukkonen, P, Macedo, P, Mansour, D, Mantzoros, C, Marchesini, G, Marciano, S, Martinez, K, Vladimirova Mateva, L, M Mato, J, Mccary, A, Miele, L, Mikolasevic, I, Miller, V, Moreno, R, Moylan, C, Nakajima, A, Charles Nault, J, Norris, S, Noureddin, M, P Oliveira, C, Ong, A, Padilla, M, Pais, R, Panduro, A, K Panigrahi, M, Papatheodoridis, G, Pelusi, S, Pérez, M, Perez Escobar, J, Perseghin, G, Pessoa, M, Petta, S, Pinzani, M, Platon Lupsor, M, Rabiee, A, Romeo, S, Rotman, Y, Rowe, I, Salupere, R, Satapathy, S, M Schattenberg, J, Schaufert, W, Schnabl, B, Seim, L, Serfaty, L, Shapiro, D, K Singal, A, Skladany, L, Stefan, N, Stine, J, Sundaram, S, Svegliati-Baroni, G, Szabo, G, Tacke, F, Tanwandee, T, Targher, G, Terrault, N, Tetri, B, Thiele, M, Tisthammer, B, Torre Delgadillo, A, Trauner, M, Tsochatzis, E, Van Kleef, L, Van Mil, S, Vanwagner, L, Antonio Velarde Ruiz Velasco, J, Vesterhus, M, Vilar-Gomez, E, Watt, K, Wattacheril, J, Wilkins, F, Willemse, J, Zekry, A, Zelber-Sagi, S, Rinella, Mary E, Lazarus, Jeffrey V, Ratziu, Vlad, Francque, Sven M, Sanyal, Arun J, Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F, Anstee, Quentin M, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher, Castro Narro, Graciela E, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna, Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D, Harrison, Stephen A, Kim, Seung Up, Koot, Bart, Korenjak, Marko, Kowdley, Kris, Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R, Powell, Elisabeth, Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C, Spearman, C Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B, Wai-Sun Wong, Vincent, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Philip NVeeral Ajmeral, William Alazawi, Maryam Alkhatry, Naim Alkhouri, Alina Allen, Michael Allison, Khalid Alswat, Mario R Alvares-da-Silva, Michele Alves-Bezerra, Matthew J Armstrong, Diego Arufe, Pablo Aschner, Gyorgy Baffy, Meena Bansal, Pierre Bedossa, Renata Belfort, Thomas Berg, Annalisa Berzigotti, Michael Betel, Cristiana Bianco, Clifford Brass, Carol L Brosgart, Elizabeth Matthews Brunt, Maria Buti, Steve Caldwell, Rotonya Carr, Teresa Casanovas, Laurent Castera, Cyrielle Caussy, Eira Cerda, Naga Chalasani, Wah Kheong Chan, Phunchai Charatcharoenwitthaya, Michael Charlton, Amanda Cheung, Daniela Chiodi, Ray Chung, David Cohen, Kathleen Corey, Helma P Cotrim, Javier Crespo, Anuradha Dassanayake, Nicholas Davidson, Robert De Knegt, Victor De Ledinghen, Münevver Demir, Sebastian Diaz, Anna Mae Diehl, Bruce Dimmig, Melisa Dirchwolf, Ajay Duseja, Karel Dvorak, Mattias Ekstedt, Reda El Wakil, María Lucía Ferraz, Scott Friedman, Michael Fuchs, Amalia Gastaldelli, Anja Geerts, Andreas Geier, Marcos Girala, George Goh, Nicolas Goossens, Isabel Graupera, Hannes Hagström, Zachary Henry, Bela Hunyady, Alan Hutchison, Scott Isaacs, François Jornayvaz, Cynthia Kemp, Denise Kile, Won Kim, David Kleiner, Rohit Kohli, Marcelo Kugelmas, Joel Lavine, Mariana Lazo, Nathalie Leite, Adelina Lozano, Panu Luukkonen, Paula Macedo, Dina Mansour, Christos Mantzoros, Giulio Marchesini, Sebastián Marciano, Kim Martinez, Lyudmila Vladimirova Mateva, Jose M Mato, Alexis McCary, Luca Miele, Ivana Mikolasevic, Veronica Miller, Rosalba Moreno, Cynthia Moylan, Atsushi Nakajima, Jean Charles Nault, Suzanne Norris, Mazen Noureddin, C P Oliveira, Arlin Ong, Martín Padilla, Raluca Pais, Arturo Panduro, Manas K Panigrahi, George Papatheodoridis, Serena Pelusi, Marlene Pérez, Juanita Perez Escobar, Gianluca Perseghin, Mario Pessoa, Salvatore Petta, Massimo Pinzani, Monica Platon Lupsor, Atoosa Rabiee, Stefano Romeo, Yaron Rotman, Ian Rowe, Riina Salupere, Sanjaya Satapathy, Jörn M Schattenberg, Wendy Schaufert, Bernd Schnabl, Lynn Seim, Lawrence Serfaty, David Shapiro, Ashwani K Singal, Lubomir Skladany, Norbert Stefan, Jonathan Stine, Shikha Sundaram, Gianluca Svegliati-Baroni, Gyonzgi Szabo, Frank Tacke, Tawesak Tanwandee, Giovanni Targher, Norah Terrault, Brent Tetri, Maja Thiele, Baron Tisthammer, Aldo Torre Delgadillo, Michael Trauner, Emmanuel Tsochatzis, Laurens Van Kleef, Saskia Van Mil, Lisa VanWagner, Jose Antonio Velarde Ruiz Velasco, Mette Vesterhus, Eduardo Vilar-Gomez, Kymberly Watt, Julia Wattacheril, Fonda Wilkins, José Willemse, Amany Zekry, and Shira Zelber-Sagi

Abstract

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms “nonalcoholic” and “fatty” were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction–associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction–associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction–associated steatotic liver disease, who consume greater amounts of alcohol per week (140–350 g/wk and 210–420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmati

Published
2023

2. Insulin degludec and glutamine dipeptide modify glucose homeostasis and liver metabolism in diabetic mice undergoing insulin-induced hypoglycemia

Author

Maria Montserrat Dias Pedrosa, Silvia C. S. F. Azevedo, Isabela Ramos Mariano, Vilma A. Ferreira Godoy, Valder Nogueira Freire, Maria Raquel Marçal Natali, Lívia Bracht, Anacharis Babeto de Sá-Nakanishi, Camila Bataglini, Rosane Marina Peralta, Adelar Bracht, and Jurandir Fernando Comar

Subjects
Blood Glucose, Male, Insulin degludec, medicine.medical_specialty, Glycogenolysis, Glutamine, Health, Toxicology and Mutagenesis, Insulins, Biomedical Engineering, Hypoglycemia, General Biochemistry, Genetics and Molecular Biology, Diabetes Mellitus, Experimental, Mice, Artificial Intelligence, Internal medicine, medicine, Animals, Homeostasis, Insulin, Glucose homeostasis, General Pharmacology, Toxicology and Pharmaceutics, Triglycerides, General Immunology and Microbiology, medicine.diagnostic_test, business.industry, General Neuroscience, Dipeptides, General Medicine, medicine.disease, Insulin, Long-Acting, Diabetes Mellitus, Type 1, Glucose, Endocrinology, Liver, Gluconeogenesis, Regular insulin, General Agricultural and Biological Sciences, Lipid profile, business
Abstract

This study investigated whether a 30-day co-treatment with 1 g/kg glutamine dipeptide (GdiP) and 1 U/kg regular (rapid acting) or 5 U/kg degludec (long acting) insulins modifies glucose homeostasis and liver metabolism of alloxan-induced type 1 diabetic (T1D) male Swiss mice undergoing insulin-induced hypoglycemia (IIH). Glycemic curves were measured in fasted mice after IIH with 1 U/kg regular insulin. One hour after IIH, the lipid profile and AST and ALT activities were assayed in the serum. Morphometric analysis was assessed in the liver sections stained with hematoxylin-eosin and glycolysis, glycogenolysis, gluconeogenesis and ureagenesis were evaluated in perfused livers. T1D mice receiving GdiP or the insulins had a smaller blood glucose drop at 60 minutes after IIH, which was not sustained during the subsequent period up to 300 minutes. The 30-day treatment of T1D mice with insulin degludec, but not with regular insulin, improved fasting glycemia, body weight gain and serum activity of AST and ALT. Treatments with insulin degludec, GdiP and insulin degludec + GdiP decreased the liver capacity in synthesizing glucose from alanine. GdiP, in combination with both insulins, was associated with increases in the serum triglycerides and, in addition, regular insulin and GdiP increased AST and ALT activities, which could be the consequence of hepatic glycogen overload. GdiP and the insulins improved the IIH, although to a small extent. Caution is recommended, however, with respect to the use of GdiP because of its increasing effects on serum triglycerides and AST plus ALT activities.

Published
2021

6. Supplementation with L-Glutamine and L-Alanyl-L-Glutamine Changes Biochemical Parameters and Jejunum Morphophysiology in Type 1 Diabetic Wistar Rats.

Author

Carlos Vinicius D da Rosa, Silvia C S F Azevedo, Roberto B Bazotte, Rosane M Peralta, Nilza C Buttow, Maria Montserrat D Pedrosa, Vilma A F de Godoi, and Maria Raquel M Natali

Subjects
Medicine, Science
Abstract

We evaluated the effects of the supplementation with L-glutamine and glutamine dipeptide (GDP) on biochemical and morphophysiological parameters in streptozotocin-diabetic rats. For this purpose, thirty animals were distributed into six groups treated orally (gavage) during thirty days: non diabetic rats (Control) + saline, diabetic + saline; Control + L-glutamine (248 mg/kg), Diabetic + L-glutamine (248 mg/kg), Control + GDP (400 mg/kg), Diabetic + GDP (400 mg/kg). Diabetes was induced by an intravenous injection of streptozotocin (60 mg/kg) and confirmed by fasting glucose ≥ 200 mg/dL. Physiological parameters, i.e., body mass, food intake, blood glucose, water intake, urine and faeces were evaluated during supplementation. After the period of supplementation, the animals were euthanized. The blood was collected for biochemical assays (fructosamine, transaminases, lipid profile, total protein, urea, ammonia). Moreover, the jejunum was excised and stored for morphophysiological assays (intestinal enzyme activity, intestinal wall morphology, crypt proliferative index, number of serotoninergic cells from the mucosa, and vipergic neurons from the submucosal tunica). The physiological parameters, protein metabolism and intestinal enzyme activity did not change with the supplementation with L-glutamine or GDP. In diabetic animals, transaminases and fructosamine improved with L-glutamine and GDP supplementations, while the lipid profile improved with L-glutamine. Furthermore, both forms of supplementation promoted changes in jejunal tunicas and wall morphometry of control and diabetic groups, but only L-glutamine promoted maintenance of serotoninergic cells and vipergic neurons populations. On the other hand, control animals showed changes that may indicate negative effects of L-glutamine. Thus, the supplementation with L-glutamine was more efficient for maintaining intestinal morphophysiology and the supplementation with GDP was more efficient to the organism as a whole. Thus, we can conclude that local differences in absorption and metabolism could explain the differences between the supplementation with L-glutamine or GDP.

Published
2015
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8. Differential Responses of Liver and Hypothalamus to the Nutritional Condition During Lactation and Adult Life

Author

Silvia C. S. F. Azevedo, Renan Soares Rabassi, Camila Bataglini, Isabela Ramos Mariano, Vanessa Lara Rissi Sabino, Maria Montserrat Diaz Pedrosa, Laís Akemi Yamada, and Rosângela Fernandes Garcia

Subjects
0301 basic medicine, Litter (animal), medicine.medical_specialty, Physiology, Neuropeptide, 030209 endocrinology & metabolism, Biology, Carbohydrate metabolism, lcsh:Physiology, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Lactation, Internal medicine, Orexigenic, medicine, hypothalamus, liver metabolism, Original Research, refeeding, lcsh:QP1-981, Neuropeptide Y receptor, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Basal (medicine), Hypothalamus, caloric restriction, litter size, medicine.drug
Abstract

It was previously reported that liver glucose metabolism in rats under caloric restriction differs from that of freely-fed rats. This study hypothesized that these changes (1) were related to the expression of hypothalamic neuropeptides involved in metabolic control, and (2) were not a residual effect of litter size. To those purposes, liver glucose metabolism and hypothalamic expression of the orexigenic neuropeptides NPY (neuropeptide Y) and AgRP (agouti gene-related peptide); and of the anorexigenic neuropeptides POMC (pro-opiomelanocortin) and CART (cocaine- and amphetamine-related transcripts) were investigated. Male Wistar rats from two different litter sizes (G6 and G12, with 6 or 12 pups, respectively) were subjected to free feeding (GL, ad libitum), 50% caloric restriction (GR) or caloric restriction+ad libitum refeeding (GRL) until the age of 90 days. Biometric values were lower in GR than in GL, while in GRL they were totally or partially recovered. Blood glucose variation during the pyruvate tolerance test (PTT) was small in GR. During in situ liver perfusion, total, basal, and adrenaline-stimulated liver glucose outputs were high in GR, but additional glucose output in the presence of alanine was negligible. Refeeding (GRL) yielded values close to those of GL. Litter size did not consistently influence any of these variables. The expression of transcripts of the hypothalamic neuropeptides was responsive to feeding regimen, litter size and/or their interaction and differed from G6 to G12, while the metabolic changes of the liver were qualitatively equal in both GR. Therefore, the changes in glucose metabolism in the liver of rats under caloric restriction were not determined by either litter size or hypothalamic neuropeptide expression and were linked only to the prevailing feeding regimen of the adult animal.

Published
2020

9. Modulation of liver glucose output by free or restricted feeding in the adult rat is independent of litter size

Author

Nayra Thais Delatorre Branquinho, Vanessa Lara Rissi Sabino, Silvia C. S. F. Azevedo, Mirian Ayumi Kurauti, Renan Soares Rabassi, Camila Bataglini, Maria Montserrat Diaz Pedrosa, Rosângela Fernandes Garcia, Laís Akemi Yamada, and Isabela Ramos Mariano

Subjects
medicine.medical_specialty, Glycogenolysis, Endocrinology, Diabetes and Metabolism, Caloric restriction, Medicine (miscellaneous), lcsh:TX341-641, 030209 endocrinology & metabolism, Carbohydrate metabolism, Glucagon, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Lactation, Metabolic programming, medicine, Glucose homeostasis, Ingestion, lcsh:RC620-627, 030304 developmental biology, 0303 health sciences, Nutrition and Dietetics, Chemistry, Research, Gluconeogenesis, lcsh:Nutritional diseases. Deficiency diseases, Litter size, medicine.anatomical_structure, Endocrinology, Basal (medicine), Liver metabolism, lcsh:Nutrition. Foods and food supply
Abstract

BackgroundCaloric restriction since birth changes glucose metabolism by the liver in overnight-fasted rats to a fed-like pattern, in which glucose output is large but gluconeogenesis is negligible. It was investigated whether these changes could be a residual effect of the nutritional condition during lactation and what could be the mechanism of such change.MethodsNewbornWistarrat pups were arranged in litters of 6 or 12 (G6 and G12). After weaning, the male pups were divided in: G6L and G12 L, fed freely until the age of 90 days (freely-fed groups); G6R and G12R, given 50% of the GL ingestion (food-restricted groups) until 90 days of age; G6RL and G12RL, given 50% of the GL ingestion until 60 days of age and fed freely until 90 days of age (refed groups). The experimental protocols were carried out at the age of 90 days after overnight fasting. Pairs of groups were compared through t test; other statistical comparisons were made with one-way ANOVA with Tukey post hoc text.ResultsCaloric restriction was effective in decreasing body and fat weights, total cholesterol and LDL. These effects were totally or partially reversed after 30 days of refeeding (groups GRL). During liver perfusion, the high glucose output of the GRs was further enhanced by adrenaline (1 μM), but not by lactate infusion. In contrast, in groups G6L, G12 L, G6RL and G12RL glycogenolysis (basal and adrenaline-stimulated glucose output) was low and gluconeogenesis from lactate was significant. A twofold increase in liver content of PKA in group G6R suggests that liver sensitivity to glucagon and adrenaline was higher because of caloric restriction, resulting in enhanced glucose output.ConclusionsAs glucose output was not affected by litter size, liver glucose metabolism in the adult rat, in contrast to other metabolic processes, is not a programmed effect of the nutritional condition during lactation. In addition, the increased expression of PKA points to a higher sensitivity of the animals under caloric restriction to glycogenolytic hormones, a relevant condition for glucose homeostasis during fasting.

Published
2019

13. Responses of the Adult Rat Glucose Metabolism to Early Life Feeding, Caloric Restriction and Refeeding

Author

Vilma Aparecida Ferreira de Godoi, Silvia C. S. F. Azevedo, M.N. Brito, Nayra Thais Delatorre Branquinho, Letícia Diniz Crepaldi, Camila Bataglini, Mônica S. M. Loiola, Maria Montserrat Diaz Pedrosa, Maria Raquel Marçal Natali, and Laís Akemi Yamada

Subjects
0301 basic medicine, Litter (animal), medicine.medical_specialty, Chemistry, Caloric theory, Carbohydrate metabolism, Hypoglycemia, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Endocrinology, Insulin resistance, medicine.anatomical_structure, Basal (medicine), In vivo, 030220 oncology & carcinogenesis, Internal medicine, Hepatocyte, medicine
Abstract

Early life overfeeding in the rat can be experimentally induced by reducing litter size. This investigation assessed the consequences of this manipulation on glucose metabolism in vivo and in isolated hepatocytes in 150-day old rats. Additionally, after body growth, the effects of caloric restriction and refeeding were tested. Adult rats from control (G9) and reduced litters (G3L) did not differ in body and fat weights, glucose tolerance or insulin resistance (insulin-induced hypoglycemia), or hepatocyte glucose release under basal or gluconeogenic conditions. Caloric restriction (G3R) reduced body and fat weights, decreased glucose decay after insulin injection and decreased hepatocyte gluconeogenic glucose release. Refeeding after caloric restriction reversed these parameters to those of the freely-fed groups (G9 and G3L). Taken together, these results suggest that the liver glucose metabolism is not programmed by lactational overfeeding, but rather is responsive to the current nutritional condition of the animal.

Published
2018

14. QUALIDADE DE PASTAS DE CEBOLA /QUALITY OF ONION CREAMS

Author

PATRÍCIA PRATI, SHIRLEY A.GARCIA BERBARI, and SILVIA C. S. ROLIM DE MOURA

Subjects
lcsh:Biotechnology, lcsh:TP248.13-248.65, lcsh:Environmental technology. Sanitary engineering, lcsh:Science (General), lcsh:TD1-1066, lcsh:Q1-390
Abstract

RESUMOO objetivo da pesquisa foi avaliar o efeito de diferentes métodos de conservação sobre a qualidade de pasta de cebola armazenada à temperatura ambiente (25ºC). Foram testados três métodos de conservação do produto envasado em vidros: branqueamento da pasta após trituração, seguido de enchimento à quente (BD); branqueamento da matéria-prima antes da trituração, seguido de exaustão e pasteurização (BA); e, branqueamento da matéria-prima antes da trituração, adição de conservante químico e envase a frio em embalagens de vidro (CV) e potes plásticos (CP). Os produtos processados foram estocados por 90 dias, sendo avaliados no tempo zero e a cada 30 dias através de análises objetivas de cor e análise sensorial dos atributos aparência, cor, odor e sabor. Os resultados foram avaliados estatisticamente através do teste de médias (Tukey) e Análise de Variância (ANOVA). Em relação à avaliação objetiva de cor, todas as amostras apresentaram escurecimento durante o tempo de estocagem. As avaliações sensoriais revelaram que apenas o atributo odor sofreu queda significativa no decorrer do armazenamento das amostras CV e BA. Os demais atributos não apresentaram alterações significativas durante o tempo de avaliação. As amostras tratadas quimicamente apresentaram melhor aparência e cor, que sãofatores importantes para o consumidor.Palavras-chaves: Hortaliças, Conservação, Avaliação Sensorial.

Published
2008

15. Supplementation with L-Glutamine and L-Alanyl-L-Glutamine Changes Biochemical Parameters and Jejunum Morphophysiology in Type 1 Diabetic Wistar Rats

Author

Vilma Aparecida Ferreira de Godoi, Rosane Marina Peralta, Maria Montserrat Diaz Pedrosa, Roberto Barbosa Bazotte, Maria Raquel Marçal Natali, Carlos Vinícius Dalto da Rosa, Silvia C. S. F. Azevedo, and Nilza Cristina Buttow

Subjects
Blood Glucose, Male, medicine.medical_specialty, Glutamine, Protein metabolism, lcsh:Medicine, Biology, Intestinal absorption, Diabetes Mellitus, Experimental, Jejunum, chemistry.chemical_compound, Internal medicine, Diabetes mellitus, medicine, Animals, Rats, Wistar, lcsh:Science, Multidisciplinary, lcsh:R, Dipeptides, Metabolism, Streptozotocin, medicine.disease, Rats, Fructosamine, Endocrinology, medicine.anatomical_structure, Intestinal Absorption, chemistry, Dietary Supplements, lcsh:Q, Research Article, medicine.drug
Abstract

We evaluated the effects of the supplementation with L-glutamine and glutamine dipeptide (GDP) on biochemical and morphophysiological parameters in streptozotocin-diabetic rats. For this purpose, thirty animals were distributed into six groups treated orally (gavage) during thirty days: non diabetic rats (Control) + saline, diabetic + saline; Control + L-glutamine (248 mg/kg), Diabetic + L-glutamine (248 mg/kg), Control + GDP (400 mg/kg), Diabetic + GDP (400 mg/kg). Diabetes was induced by an intravenous injection of streptozotocin (60 mg/kg) and confirmed by fasting glucose ≥ 200 mg/dL. Physiological parameters, i.e., body mass, food intake, blood glucose, water intake, urine and faeces were evaluated during supplementation. After the period of supplementation, the animals were euthanized. The blood was collected for biochemical assays (fructosamine, transaminases, lipid profile, total protein, urea, ammonia). Moreover, the jejunum was excised and stored for morphophysiological assays (intestinal enzyme activity, intestinal wall morphology, crypt proliferative index, number of serotoninergic cells from the mucosa, and vipergic neurons from the submucosal tunica). The physiological parameters, protein metabolism and intestinal enzyme activity did not change with the supplementation with L-glutamine or GDP. In diabetic animals, transaminases and fructosamine improved with L-glutamine and GDP supplementations, while the lipid profile improved with L-glutamine. Furthermore, both forms of supplementation promoted changes in jejunal tunicas and wall morphometry of control and diabetic groups, but only L-glutamine promoted maintenance of serotoninergic cells and vipergic neurons populations. On the other hand, control animals showed changes that may indicate negative effects of L-glutamine. Thus, the supplementation with L-glutamine was more efficient for maintaining intestinal morphophysiology and the supplementation with GDP was more efficient to the organism as a whole. Thus, we can conclude that local differences in absorption and metabolism could explain the differences between the supplementation with L-glutamine or GDP.

Published
2015

19. A multi-society Delphi consensus statement on new fatty liver disease nomenclature

Author

Rinella, Mary E, Lazarus, Jeffrey V, Ratziu, Vlad, Francque, Sven M, Sanyal, Arun J, Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F, Anstee, Quentin M, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher, Castro Narro, Graciela E, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna, Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D, Harrison, Stephen A, Kim, Seung Up, Koot, Bart, Korenjak, Marko, Kowdley, Kris, Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R, Powell, Elisabeth, Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C, Spearman, C Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B, Wong, Vincent Wai-Sun, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Newsome, Philip NVeeral Ajmeral, William Alazawi, Maryam Alkhatry, Naim Alkhouri, Alina Allen, Michael Allison, Khalid Alswat, Mario R Alvares-da-Silva, Michele Alves-Bezerra, Matthew J Armstrong, Diego Arufe, Pablo Aschner, Gyorgy Baffy, Meena Bansal, Pierre Bedossa, Renata Belfort, Thomas Berg, Annalisa Berzigotti, Michael Betel, Cristiana Bianco, Clifford Brass, Carol L Brosgart, Elizabeth Matthews Brunt, Maria Buti, Steve Caldwell, Rotonya Carr, Teresa Casanovas, Laurent Castera, Cyrielle Caussy, Eira Cerda, Naga Chalasani, Wah Kheong Chan, Phunchai Charatcharoenwitthaya, Michael Charlton, Amanda Cheung, Daniela Chiodi, Ray Chung, David Cohen, Kathleen Corey, Helma P Cotrim, Javier Crespo, Anuradha Dassanayake, Nicholas Davidson, Robert De Knegt, Victor De Ledinghen, Münevver Demir, Sebastian Diaz, Anna Mae Diehl, Bruce Dimmig, Melisa Dirchwolf, Ajay Duseja, Karel Dvorak, Mattias Ekstedt, Reda El Wakil, María Lucía Ferraz, Scott Friedman, Michael Fuchs, Amalia Gastaldelli, Anja Geerts, Andreas Geier, Marcos Girala, George Goh, Nicolas Goossens, Isabel Graupera, Hannes Hagström, Zachary Henry, Bela Hunyady, Alan Hutchison, Scott Isaacs, François Jornayvaz, Cynthia Kemp, Denise Kile, Won Kim, David Kleiner, Rohit Kohli, Marcelo Kugelmas, Joel Lavine, Mariana Lazo, Nathalie Leite, Adelina Lozano, Panu Luukkonen, Paula Macedo, Dina Mansour, Christos Mantzoros, Giulio Marchesini, Sebastián Marciano, Kim Martinez, Lyudmila Vladimirova Mateva, Jose M Mato, Alexis McCary, Luca Miele, Ivana Mikolasevic, Veronica Miller, Rosalba Moreno, Cynthia Moylan, Atsushi Nakajima, Jean Charles Nault, Suzanne Norris, Mazen Noureddin, C P Oliveira, Arlin Ong, Martín Padilla, Raluca Pais, Arturo Panduro, Manas K Panigrahi, George Papatheodoridis, Serena Pelusi, Marlene Pérez, Juanita Perez Escobar, Gianluca Perseghin, Mario Pessoa, Salvatore Petta, Massimo Pinzani, Monica Platon Lupsor, Atoosa Rabiee, Stefano Romeo, Yaron Rotman, Ian Rowe, Riina Salupere, Sanjaya Satapathy, Jörn M Schattenberg, Wendy Schaufert, Bernd Schnabl, Lynn Seim, Lawrence Serfaty, David Shapiro, Ashwani K Singal, Lubomir Skladany, Norbert Stefan, Jonathan Stine, Shikha Sundaram, Gianluca Svegliati-Baroni, Gyonzgi Szabo, Frank Tacke, Tawesak Tanwandee, Giovanni Targher, Norah Terrault, Brent Tetri, Maja Thiele, Baron Tisthammer, Aldo Torre Delgadillo, Michael Trauner, Emmanuel Tsochatzis, Laurens Van Kleef, Saskia Van Mil, Lisa VanWagner, Jose Antonio Velarde Ruiz Velasco, Mette Vesterhus, Eduardo Vilar-Gomez, Kymberly Watt, Julia Wattacheril, Fonda Wilkins, José Willemse, Amany Zekry, Shira Zelber-Sagi, Mary E, R, Jeffrey V, L, Vlad, R, Sven M, F, Arun J, S, Fasiha, K, Diana, R, Manal F, A, Quentin M, A, Juan Pablo, A, Marco, A, Ramon, B, Ulrich, B, Jerome, B, Elisabetta, B, Christopher, B, Graciela E, C, Abhijit, C, Helena, C, Donna, C, Kenneth, C, Mohamed, E, Samuel, K, Wayne, E, Jiangao, F, Samer, G, Cynthia D, G, Stephen A, H, Seung Up, K, Bart, K, Marko, K, Kris, K, Florence, L, Rohit, L, Robert, M, Timothy R, M, Elisabeth, P, Michael, R, Manuel, R, Marcelo, S, Shivaram Prasad, S, Silvia C, S, C Wendy, S, Dina, T, Luca, V, Miriam B, V, Vincent, W, Stavra, X, Yusuf, Y, Zobair, Y, Ansley, H, Marcela, V, Newsome, NVeeral Ajmeral, P, Alazawi, W, Alkhatry, M, Alkhouri, N, Allen, A, Allison, M, Alswat, K, R Alvares-da-Silva, M, Alves-Bezerra, M, J Armstrong, M, Arufe, D, Aschner, P, Baffy, G, Bansal, M, Bedossa, P, Belfort, R, Berg, T, Berzigotti, A, Betel, M, Bianco, C, Brass, C, L Brosgart, C, Matthews Brunt, E, Buti, M, Caldwell, S, Carr, R, Casanovas, T, Castera, L, Caussy, C, Cerda, E, Chalasani, N, Kheong Chan, W, Charatcharoenwitthaya, P, Charlton, M, Cheung, A, Chiodi, D, Chung, R, Cohen, D, Corey, K, P Cotrim, H, Crespo, J, Dassanayake, A, Davidson, N, De Knegt, R, De Ledinghen, V, Demir, M, Diaz, S, Mae Diehl, A, Dimmig, B, Dirchwolf, M, Duseja, A, Dvorak, K, Ekstedt, M, El Wakil, R, Lucía Ferraz, M, Friedman, S, Fuchs, M, Gastaldelli, A, Geerts, A, Geier, A, Girala, M, Goh, G, Goossens, N, Graupera, I, Hagström, H, Henry, Z, Hunyady, B, Hutchison, A, Isaacs, S, Jornayvaz, F, Kemp, C, Kile, D, Kim, W, Kleiner, D, Kohli, R, Kugelmas, M, Lavine, J, Lazo, M, Leite, N, Lozano, A, Luukkonen, P, Macedo, P, Mansour, D, Mantzoros, C, Marchesini, G, Marciano, S, Martinez, K, Vladimirova Mateva, L, M Mato, J, Mccary, A, Miele, L, Mikolasevic, I, Miller, V, Moreno, R, Moylan, C, Nakajima, A, Charles Nault, J, Norris, S, Noureddin, M, P Oliveira, C, Ong, A, Padilla, M, Pais, R, Panduro, A, K Panigrahi, M, Papatheodoridis, G, Pelusi, S, Pérez, M, Perez Escobar, J, Perseghin, G, Pessoa, M, Petta, S, Pinzani, M, Platon Lupsor, M, Rabiee, A, Romeo, S, Rotman, Y, Rowe, I, Salupere, R, Satapathy, S, M Schattenberg, J, Schaufert, W, Schnabl, B, Seim, L, Serfaty, L, Shapiro, D, K Singal, A, Skladany, L, Stefan, N, Stine, J, Sundaram, S, Svegliati-Baroni, G, Szabo, G, Tacke, F, Tanwandee, T, Targher, G, Terrault, N, Tetri, B, Thiele, M, Tisthammer, B, Torre Delgadillo, A, Trauner, M, Tsochatzis, E, Van Kleef, L, Van Mil, S, Vanwagner, L, Antonio Velarde Ruiz Velasco, J, Vesterhus, M, Vilar-Gomez, E, Watt, K, Wattacheril, J, Wilkins, F, Willemse, J, Zekry, A, Zelber-Sagi, S, and Vincent Wai-Sun, W

Subjects
steatotic liver disease, MASLD, alcohol, steatohepatiti, MetALD, NASH, nonalcoholic, Delphi, Fatty liver disease, NAFLD, cardiometabolic, nomenclature, mafld, type 2 diabetes, MED/13 - ENDOCRINOLOGIA
Abstract

Unlabelled: The principal limitations of the terms nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. Methods: A modified Delphi process was led by three large pan-national liver associations. Consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. Results: A total of 236 panellists from 56 countries participated in four online surveys and two hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83% and 78%, respectively. 74% of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms 'non-alcoholic' and 'fatty' were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease (SLD) was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least one of five cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic SLD. A new category, outside pure MASLD, termed MetALD was selected to describe those with MASLD who consume greater amounts of alcohol per week (140 to 350g/week and 210 to 420g/week for females and males respectively). Conclusions: The new nomenclature and diagnostic criteria are widely supported, non-stigmatising and can improve awareness and patient identification.

Published
2023

20. Supplementation with L-Glutamine and L-Alanyl-L-Glutamine Changes Biochemical Parameters and Jejunum Morphophysiology in Type 1 Diabetic Wistar Rats.

Author

da Rosa CV, Azevedo SC, Bazotte RB, Peralta RM, Buttow NC, Pedrosa MM, de Godoi VA, and Natali MR

Subjects
Animals, Blood Glucose metabolism, Diabetes Mellitus, Experimental blood, Diabetes Mellitus, Experimental metabolism, Dietary Supplements, Dipeptides pharmacokinetics, Glutamine pharmacokinetics, Intestinal Absorption drug effects, Jejunum metabolism, Jejunum physiopathology, Male, Rats, Rats, Wistar, Diabetes Mellitus, Experimental drug therapy, Dipeptides pharmacology, Glutamine pharmacology, Jejunum drug effects
Abstract

We evaluated the effects of the supplementation with L-glutamine and glutamine dipeptide (GDP) on biochemical and morphophysiological parameters in streptozotocin-diabetic rats. For this purpose, thirty animals were distributed into six groups treated orally (gavage) during thirty days: non diabetic rats (Control) + saline, diabetic + saline; Control + L-glutamine (248 mg/kg), Diabetic + L-glutamine (248 mg/kg), Control + GDP (400 mg/kg), Diabetic + GDP (400 mg/kg). Diabetes was induced by an intravenous injection of streptozotocin (60 mg/kg) and confirmed by fasting glucose ≥ 200 mg/dL. Physiological parameters, i.e., body mass, food intake, blood glucose, water intake, urine and faeces were evaluated during supplementation. After the period of supplementation, the animals were euthanized. The blood was collected for biochemical assays (fructosamine, transaminases, lipid profile, total protein, urea, ammonia). Moreover, the jejunum was excised and stored for morphophysiological assays (intestinal enzyme activity, intestinal wall morphology, crypt proliferative index, number of serotoninergic cells from the mucosa, and vipergic neurons from the submucosal tunica). The physiological parameters, protein metabolism and intestinal enzyme activity did not change with the supplementation with L-glutamine or GDP. In diabetic animals, transaminases and fructosamine improved with L-glutamine and GDP supplementations, while the lipid profile improved with L-glutamine. Furthermore, both forms of supplementation promoted changes in jejunal tunicas and wall morphometry of control and diabetic groups, but only L-glutamine promoted maintenance of serotoninergic cells and vipergic neurons populations. On the other hand, control animals showed changes that may indicate negative effects of L-glutamine. Thus, the supplementation with L-glutamine was more efficient for maintaining intestinal morphophysiology and the supplementation with GDP was more efficient to the organism as a whole. Thus, we can conclude that local differences in absorption and metabolism could explain the differences between the supplementation with L-glutamine or GDP.

Published
2015
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21. Nicotine-mediated signals modulate cell death and survival of T lymphocytes.

Author

Oloris SC, Frazer-Abel AA, Jubala CM, Fosmire SP, Helm KM, Robinson SR, Korpela DM, Duckett MM, Baksh S, and Modiano JF

Subjects
Humans, Jurkat Cells, Leukemia, T-Cell metabolism, Receptors, Nicotinic drug effects, Receptors, Nicotinic metabolism, Signal Transduction drug effects, T-Lymphocytes metabolism, Apoptosis drug effects, Cell Survival drug effects, Nicotine pharmacology, Nicotinic Agonists pharmacology, T-Lymphocytes drug effects
Abstract

The capacity of nicotine to affect the behavior of non-neuronal cells through neuronal nicotinic acetylcholine receptors (nAChRs) has been the subject of considerable recent attention. Previously, we showed that exposure to nicotine activates the nuclear factor of activated T cells (NFAT) transcription factor in lymphocytes and endothelial cells, leading to alterations in cellular growth and vascular endothelial growth factor production. Here, we extend these studies to document effects of nicotine on lymphocyte survival. The data show that nicotine induces paradoxical effects that might alternatively enforce survival or trigger apoptosis, suggesting that depending on timing and context, nicotine might act both as a survival factor or as an inducer of apoptosis in normal or transformed lymphocytes, and possibly other non-neuronal cells. In addition, our results show that, while having overlapping functions, low and high affinity nAChRs also transmit signals that promote distinct outcomes in lymphocytes. The sum of our data suggests that selective modulation of nAChRs might be useful to regulate lymphocyte activation and survival in health and disease., (Copyright 2009 Elsevier Inc. All rights reserved.)

Published
2010
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