Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types
We report the synthesis of a novel, Zn2+-chelating derivative of the pan-BETi (+)-JQ1, (+)-JQ1-DPA, in which (+)-JQ1 was conjugated to dipicolyl amine (DPA). As controls, we synthesized (+)-JQ1-DBA, a non-Zn2+-chelating derivative, and (-)-JQ1-DPA, an inactive enantiomer that chelates Zn2+. Molecular modeling and biophysical assays showed that (+)-JQ1-DPA and (+)-JQ1-DBA retain potent binding to BET bromodomains in vitro. Cellular assays demonstrated (+)-JQ1-DPA attenuated NF-ĸB target gene expression in β-cells stimulated with the pro-inflammatory cytokine interleukin 1β. To assess β-cell selectivity, we isolated isle...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 15, 2024 Category: Physiology Authors: Rachel A Jones Lipinski Jennifer S Stancill Raymundo Nu ñez Sarah L Wynia-Smith Daniel J Sprague Joshua A Nord Amir Bird John A Corbett Brian C Smith Source Type: research

Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types
We report the synthesis of a novel, Zn2+-chelating derivative of the pan-BETi (+)-JQ1, (+)-JQ1-DPA, in which (+)-JQ1 was conjugated to dipicolyl amine (DPA). As controls, we synthesized (+)-JQ1-DBA, a non-Zn2+-chelating derivative, and (-)-JQ1-DPA, an inactive enantiomer that chelates Zn2+. Molecular modeling and biophysical assays showed that (+)-JQ1-DPA and (+)-JQ1-DBA retain potent binding to BET bromodomains in vitro. Cellular assays demonstrated (+)-JQ1-DPA attenuated NF-ĸB target gene expression in β-cells stimulated with the pro-inflammatory cytokine interleukin 1β. To assess β-cell selectivity, we isolated isle...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 15, 2024 Category: Physiology Authors: Rachel A Jones Lipinski Jennifer S Stancill Raymundo Nu ñez Sarah L Wynia-Smith Daniel J Sprague Joshua A Nord Amir Bird John A Corbett Brian C Smith Source Type: research

ß-cell selective regulation of gene expression by nitric oxide
In this report, the time- and concentration-dependent effects of nitric oxide on the expression of 6 genes known to participate in the response of β-cells to this free radical were examined. The genes included Gadd45α (DNA repair), Puma (apoptosis), Hmox1 (antioxidant defense), Hsp70 (heat shock), Chop (UPR), and ßPpargc1α (mitochondrial biogenesis). We show that nitric oxide stimulates β-cell gene expression in a narrow concentration range of ~0.5-1 µM, or levels corresponding to iNOS-derived nitric oxide. At concentrations greater than 1 µM, nitric oxide fails to stimulate gene expression in β-cells, and this is ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 8, 2024 Category: Physiology Authors: Aaron Naatz Chay Teng Yeo Neil Hogg John A Corbett Source Type: research

Weight loss in adult male Wistar rats by Roux-en-Y gastric bypass is primarily explained by caloric intake reduction and pre-surgery body weight
Am J Physiol Regul Integr Comp Physiol. 2024 Apr 8. doi: 10.1152/ajpregu.00169.2023. Online ahead of print.ABSTRACTDiets varying in macronutrient composition, energy density, and/or palatability may cause differences in outcome of bariatric surgery. In the present study, rats feeding a healthy low fat (LF) diet or an obesogenic high fat/sucrose diet (HF/S) were either subjected to Roux-en-Y gastric bypass surgery (RYGB) or sham surgery, and weight loss trajectories and various energy balance parameters were assessed. Before RYGB, rats eating a HF/S (n=14) diet increased body weight relative to rats eating a LF diet (n=20; ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 8, 2024 Category: Physiology Authors: C Warner Hoornenborg Edit Somogyi Jan E Bruggink Christina N Boyle Thomas A Lutz Marloes Emous Andr é P van Beek Csaba Nyakas Gertjan van Dijk Source Type: research

ß-cell selective regulation of gene expression by nitric oxide
In this report, the time- and concentration-dependent effects of nitric oxide on the expression of 6 genes known to participate in the response of β-cells to this free radical were examined. The genes included Gadd45α (DNA repair), Puma (apoptosis), Hmox1 (antioxidant defense), Hsp70 (heat shock), Chop (UPR), and ßPpargc1α (mitochondrial biogenesis). We show that nitric oxide stimulates β-cell gene expression in a narrow concentration range of ~0.5-1 µM, or levels corresponding to iNOS-derived nitric oxide. At concentrations greater than 1 µM, nitric oxide fails to stimulate gene expression in β-cells, and this is ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 8, 2024 Category: Physiology Authors: Aaron Naatz Chay Teng Yeo Neil Hogg John A Corbett Source Type: research

Weight loss in adult male Wistar rats by Roux-en-Y gastric bypass is primarily explained by caloric intake reduction and pre-surgery body weight
Am J Physiol Regul Integr Comp Physiol. 2024 Apr 8. doi: 10.1152/ajpregu.00169.2023. Online ahead of print.ABSTRACTDiets varying in macronutrient composition, energy density, and/or palatability may cause differences in outcome of bariatric surgery. In the present study, rats feeding a healthy low fat (LF) diet or an obesogenic high fat/sucrose diet (HF/S) were either subjected to Roux-en-Y gastric bypass surgery (RYGB) or sham surgery, and weight loss trajectories and various energy balance parameters were assessed. Before RYGB, rats eating a HF/S (n=14) diet increased body weight relative to rats eating a LF diet (n=20; ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 8, 2024 Category: Physiology Authors: C Warner Hoornenborg Edit Somogyi Jan E Bruggink Christina N Boyle Thomas A Lutz Marloes Emous Andr é P van Beek Csaba Nyakas Gertjan van Dijk Source Type: research

ß-cell selective regulation of gene expression by nitric oxide
In this report, the time- and concentration-dependent effects of nitric oxide on the expression of 6 genes known to participate in the response of β-cells to this free radical were examined. The genes included Gadd45α (DNA repair), Puma (apoptosis), Hmox1 (antioxidant defense), Hsp70 (heat shock), Chop (UPR), and ßPpargc1α (mitochondrial biogenesis). We show that nitric oxide stimulates β-cell gene expression in a narrow concentration range of ~0.5-1 µM, or levels corresponding to iNOS-derived nitric oxide. At concentrations greater than 1 µM, nitric oxide fails to stimulate gene expression in β-cells, and this is ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 8, 2024 Category: Physiology Authors: Aaron Naatz Chay Teng Yeo Neil Hogg John A Corbett Source Type: research

Weight loss in adult male Wistar rats by Roux-en-Y gastric bypass is primarily explained by caloric intake reduction and pre-surgery body weight
Am J Physiol Regul Integr Comp Physiol. 2024 Apr 8. doi: 10.1152/ajpregu.00169.2023. Online ahead of print.ABSTRACTDiets varying in macronutrient composition, energy density, and/or palatability may cause differences in outcome of bariatric surgery. In the present study, rats feeding a healthy low fat (LF) diet or an obesogenic high fat/sucrose diet (HF/S) were either subjected to Roux-en-Y gastric bypass surgery (RYGB) or sham surgery, and weight loss trajectories and various energy balance parameters were assessed. Before RYGB, rats eating a HF/S (n=14) diet increased body weight relative to rats eating a LF diet (n=20; ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 8, 2024 Category: Physiology Authors: C Warner Hoornenborg Edit Somogyi Jan E Bruggink Christina N Boyle Thomas A Lutz Marloes Emous Andr é P van Beek Csaba Nyakas Gertjan van Dijk Source Type: research

ß-cell selective regulation of gene expression by nitric oxide
In this report, the time- and concentration-dependent effects of nitric oxide on the expression of 6 genes known to participate in the response of β-cells to this free radical were examined. The genes included Gadd45α (DNA repair), Puma (apoptosis), Hmox1 (antioxidant defense), Hsp70 (heat shock), Chop (UPR), and ßPpargc1α (mitochondrial biogenesis). We show that nitric oxide stimulates β-cell gene expression in a narrow concentration range of ~0.5-1 µM, or levels corresponding to iNOS-derived nitric oxide. At concentrations greater than 1 µM, nitric oxide fails to stimulate gene expression in β-cells, and this is ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 8, 2024 Category: Physiology Authors: Aaron Naatz Chay Teng Yeo Neil Hogg John A Corbett Source Type: research

Weight loss in adult male Wistar rats by Roux-en-Y gastric bypass is primarily explained by caloric intake reduction and pre-surgery body weight
Am J Physiol Regul Integr Comp Physiol. 2024 Apr 8. doi: 10.1152/ajpregu.00169.2023. Online ahead of print.ABSTRACTDiets varying in macronutrient composition, energy density, and/or palatability may cause differences in outcome of bariatric surgery. In the present study, rats feeding a healthy low fat (LF) diet or an obesogenic high fat/sucrose diet (HF/S) were either subjected to Roux-en-Y gastric bypass surgery (RYGB) or sham surgery, and weight loss trajectories and various energy balance parameters were assessed. Before RYGB, rats eating a HF/S (n=14) diet increased body weight relative to rats eating a LF diet (n=20; ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 8, 2024 Category: Physiology Authors: C Warner Hoornenborg Edit Somogyi Jan E Bruggink Christina N Boyle Thomas A Lutz Marloes Emous Andr é P van Beek Csaba Nyakas Gertjan van Dijk Source Type: research

ß-cell selective regulation of gene expression by nitric oxide
In this report, the time- and concentration-dependent effects of nitric oxide on the expression of 6 genes known to participate in the response of β-cells to this free radical were examined. The genes included Gadd45α (DNA repair), Puma (apoptosis), Hmox1 (antioxidant defense), Hsp70 (heat shock), Chop (UPR), and ßPpargc1α (mitochondrial biogenesis). We show that nitric oxide stimulates β-cell gene expression in a narrow concentration range of ~0.5-1 µM, or levels corresponding to iNOS-derived nitric oxide. At concentrations greater than 1 µM, nitric oxide fails to stimulate gene expression in β-cells, and this is ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 8, 2024 Category: Physiology Authors: Aaron Naatz Chay Teng Yeo Neil Hogg John A Corbett Source Type: research

Weight loss in adult male Wistar rats by Roux-en-Y gastric bypass is primarily explained by caloric intake reduction and pre-surgery body weight
Am J Physiol Regul Integr Comp Physiol. 2024 Apr 8. doi: 10.1152/ajpregu.00169.2023. Online ahead of print.ABSTRACTDiets varying in macronutrient composition, energy density, and/or palatability may cause differences in outcome of bariatric surgery. In the present study, rats feeding a healthy low fat (LF) diet or an obesogenic high fat/sucrose diet (HF/S) were either subjected to Roux-en-Y gastric bypass surgery (RYGB) or sham surgery, and weight loss trajectories and various energy balance parameters were assessed. Before RYGB, rats eating a HF/S (n=14) diet increased body weight relative to rats eating a LF diet (n=20; ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 8, 2024 Category: Physiology Authors: C Warner Hoornenborg Edit Somogyi Jan E Bruggink Christina N Boyle Thomas A Lutz Marloes Emous Andr é P van Beek Csaba Nyakas Gertjan van Dijk Source Type: research

Alterations of Whole-Body Glucose Metabolism in a Feline SARS-CoV-2 Infection Model
Am J Physiol Regul Integr Comp Physiol. 2024 Apr 4. doi: 10.1152/ajpregu.00228.2023. Online ahead of print.ABSTRACTSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been especially devastating to patients with comorbidities, including metabolic and cardiovascular diseases. Elevated blood glucose during SARS-CoV-2 infection increased mortality of COVID-19 patients, although the mechanisms are not well understood. It has been previously demonstrated that glucose transport and utilization is a crucial pathway for other highly infectious RNA viruses. Thus, we hypothesized that SARS-CoV-2 infection could lead to ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 4, 2024 Category: Physiology Authors: Matthew T Rochowski Kaushalya Jayathilake John-Michael Balcerak Miruthula Tamil Selvan Sachithra Gunasekara Jennifer Rudd Craig Miller V éronique A Lacombe Source Type: research

Alterations of Whole-Body Glucose Metabolism in a Feline SARS-CoV-2 Infection Model
Am J Physiol Regul Integr Comp Physiol. 2024 Apr 4. doi: 10.1152/ajpregu.00228.2023. Online ahead of print.ABSTRACTSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been especially devastating to patients with comorbidities, including metabolic and cardiovascular diseases. Elevated blood glucose during SARS-CoV-2 infection increased mortality of COVID-19 patients, although the mechanisms are not well understood. It has been previously demonstrated that glucose transport and utilization is a crucial pathway for other highly infectious RNA viruses. Thus, we hypothesized that SARS-CoV-2 infection could lead to ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 4, 2024 Category: Physiology Authors: Matthew T Rochowski Kaushalya Jayathilake John-Michael Balcerak Miruthula Tamil Selvan Sachithra Gunasekara Jennifer Rudd Craig Miller V éronique A Lacombe Source Type: research

Alterations of Whole-Body Glucose Metabolism in a Feline SARS-CoV-2 Infection Model
Am J Physiol Regul Integr Comp Physiol. 2024 Apr 4. doi: 10.1152/ajpregu.00228.2023. Online ahead of print.ABSTRACTSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been especially devastating to patients with comorbidities, including metabolic and cardiovascular diseases. Elevated blood glucose during SARS-CoV-2 infection increased mortality of COVID-19 patients, although the mechanisms are not well understood. It has been previously demonstrated that glucose transport and utilization is a crucial pathway for other highly infectious RNA viruses. Thus, we hypothesized that SARS-CoV-2 infection could lead to ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - April 4, 2024 Category: Physiology Authors: Matthew T Rochowski Kaushalya Jayathilake John-Michael Balcerak Miruthula Tamil Selvan Sachithra Gunasekara Jennifer Rudd Craig Miller V éronique A Lacombe Source Type: research