Publications
ULB CENTER FOR DIABETES RESEARCH
2017
Baroj Abdulkarim; Miriam Hernangomez; Mariana Igoillo-Esteve; Daniel A Cunha; Lorella Marselli; Piero Marchetti; Laurence Ladriere; Miriam Cnop
Guanabenz Sensitizes Pancreatic β Cells to Lipotoxic Endoplasmic Reticulum Stress and Apoptosis Journal Article
In: Endocrinology, vol. 158, no. 6, pp. 1659–1670, 2017, ISSN: 1945-7170.
@article{pmid28323924,
title = {Guanabenz Sensitizes Pancreatic β Cells to Lipotoxic Endoplasmic Reticulum Stress and Apoptosis},
author = {Baroj Abdulkarim and Miriam Hernangomez and Mariana Igoillo-Esteve and Daniel A Cunha and Lorella Marselli and Piero Marchetti and Laurence Ladriere and Miriam Cnop},
doi = {10.1210/en.2016-1773},
issn = {1945-7170},
year = {2017},
date = {2017-06-01},
journal = {Endocrinology},
volume = {158},
number = {6},
pages = {1659--1670},
abstract = {Deficient as well as excessive/prolonged endoplasmic reticulum (ER) stress signaling can lead to pancreatic β cell failure and the development of diabetes. Saturated free fatty acids (FFAs) such as palmitate induce lipotoxic ER stress in pancreatic β cells. One of the main ER stress response pathways is under the control of the protein kinase R-like endoplasmic reticulum kinase (PERK), leading to phosphorylation of the eukaryotic translation initiation factor 2 (eIF2α). The antihypertensive drug guanabenz has been shown to inhibit eIF2α dephosphorylation and protect cells from ER stress. Here we examined whether guanabenz protects pancreatic β cells from lipotoxicity. Guanabenz induced β cell dysfunction in vitro and in vivo in rodents and led to impaired glucose tolerance. The drug significantly potentiated FFA-induced cell death in clonal rat β cells and in rat and human islets. Guanabenz enhanced FFA-induced eIF2α phosphorylation and expression of the downstream proapoptotic gene C/EBP homologous protein (CHOP), which mediated the sensitization to lipotoxicity. Thus, guanabenz does not protect β cells from ER stress; instead, it potentiates lipotoxic ER stress through PERK/eIF2α/CHOP signaling. These data demonstrate the crucial importance of the tight regulation of eIF2α phosphorylation for the normal function and survival of pancreatic β cells.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Deficient as well as excessive/prolonged endoplasmic reticulum (ER) stress signaling can lead to pancreatic β cell failure and the development of diabetes. Saturated free fatty acids (FFAs) such as palmitate induce lipotoxic ER stress in pancreatic β cells. One of the main ER stress response pathways is under the control of the protein kinase R-like endoplasmic reticulum kinase (PERK), leading to phosphorylation of the eukaryotic translation initiation factor 2 (eIF2α). The antihypertensive drug guanabenz has been shown to inhibit eIF2α dephosphorylation and protect cells from ER stress. Here we examined whether guanabenz protects pancreatic β cells from lipotoxicity. Guanabenz induced β cell dysfunction in vitro and in vivo in rodents and led to impaired glucose tolerance. The drug significantly potentiated FFA-induced cell death in clonal rat β cells and in rat and human islets. Guanabenz enhanced FFA-induced eIF2α phosphorylation and expression of the downstream proapoptotic gene C/EBP homologous protein (CHOP), which mediated the sensitization to lipotoxicity. Thus, guanabenz does not protect β cells from ER stress; instead, it potentiates lipotoxic ER stress through PERK/eIF2α/CHOP signaling. These data demonstrate the crucial importance of the tight regulation of eIF2α phosphorylation for the normal function and survival of pancreatic β cells.
Marina Boscolo; Francoise Féry; Miriam Cnop
Beneficial Outcomes of Sleeve Gastrectomy in a Morbidly Obese Patient With Bardet-Biedl Syndrome
2017.
@{pmid29264490,
title = {Beneficial Outcomes of Sleeve Gastrectomy in a Morbidly Obese Patient With Bardet-Biedl Syndrome},
author = {Marina Boscolo and Francoise Féry and Miriam Cnop},
doi = {10.1210/js.2017-00071},
issn = {2472-1972},
year = {2017},
date = {2017-04-01},
journal = {J Endocr Soc},
volume = {1},
number = {4},
pages = {317--322},
abstract = {CONTEXT: Severe obesity is one of the major features of Bardet-Biedl syndrome (BBS) and causes reduced life expectancy. Bariatric surgery is an effective treatment of morbid obesity. Data on the effect of bariatric surgery for monogenic obesity is essentially lacking. We present the clinical and metabolic 3-year follow-up of sleeve gastrectomy in a BBS patient.
CASE DESCRIPTION: A 37-year-old obese woman with BBS (body mass index, 40 kg/m) was referred to our clinic for uncontrolled diabetes, dyslipidemia, hypertension, and nonalcoholic fatty liver disease (NAFLD). After sleeve gastrectomy, progressive weight loss was observed, with a 32% total weight loss at 3-year follow-up. Glycemic control and NAFLD improved significantly. Blood pressure normalized, and treatment was discontinued 3 months after surgery.
CONCLUSIONS: Laparoscopic sleeve gastrectomy can be a safe and effective treatment of morbid BBS-related obesity in adult patients. Significant and sustained weight loss leads to the improvement of several obesity-related comorbidities such as diabetes, hypertension, and NAFLD, as in polygenic obesity. Further data are needed to confirm the long-term efficacy and safety of bariatric surgery in BBS.},
keywords = {},
pubstate = {published},
tppubtype = {}
}
CONTEXT: Severe obesity is one of the major features of Bardet-Biedl syndrome (BBS) and causes reduced life expectancy. Bariatric surgery is an effective treatment of morbid obesity. Data on the effect of bariatric surgery for monogenic obesity is essentially lacking. We present the clinical and metabolic 3-year follow-up of sleeve gastrectomy in a BBS patient.
CASE DESCRIPTION: A 37-year-old obese woman with BBS (body mass index, 40 kg/m) was referred to our clinic for uncontrolled diabetes, dyslipidemia, hypertension, and nonalcoholic fatty liver disease (NAFLD). After sleeve gastrectomy, progressive weight loss was observed, with a 32% total weight loss at 3-year follow-up. Glycemic control and NAFLD improved significantly. Blood pressure normalized, and treatment was discontinued 3 months after surgery.
CONCLUSIONS: Laparoscopic sleeve gastrectomy can be a safe and effective treatment of morbid BBS-related obesity in adult patients. Significant and sustained weight loss leads to the improvement of several obesity-related comorbidities such as diabetes, hypertension, and NAFLD, as in polygenic obesity. Further data are needed to confirm the long-term efficacy and safety of bariatric surgery in BBS.
CASE DESCRIPTION: A 37-year-old obese woman with BBS (body mass index, 40 kg/m) was referred to our clinic for uncontrolled diabetes, dyslipidemia, hypertension, and nonalcoholic fatty liver disease (NAFLD). After sleeve gastrectomy, progressive weight loss was observed, with a 32% total weight loss at 3-year follow-up. Glycemic control and NAFLD improved significantly. Blood pressure normalized, and treatment was discontinued 3 months after surgery.
CONCLUSIONS: Laparoscopic sleeve gastrectomy can be a safe and effective treatment of morbid BBS-related obesity in adult patients. Significant and sustained weight loss leads to the improvement of several obesity-related comorbidities such as diabetes, hypertension, and NAFLD, as in polygenic obesity. Further data are needed to confirm the long-term efficacy and safety of bariatric surgery in BBS.
