Understanding Carbohydrate Metabolism and Insulin Resistance in Acute Intermittent Porphyria
Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks associated with high production, accumulation and urinary excretion of heme precursors, δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). The estimated clinical pene...
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/72333 |
| Acceso en línea: | https://hdl.handle.net/20.500.14352/72333 |
| Access Level: | acceso abierto |
| Palabra clave: | 616.3 Hepatic porphyrias Acute intermittent porphyria Fasting Glucose homeostasis Insulin resistance Mitochondrial function and biogenesis Medicina Endocrinología Gastroenterología y hepatología Medicina interna 32 Ciencias Médicas 3205.02 Endocrinología 3205.03 Gastroenterología 3205 Medicina Interna |
| id |
ES_d8c0bd1fbcfe626fda4608a9d0d843a2 |
|---|---|
| oai_identifier_str |
oai:docta.ucm.es:20.500.14352/72333 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| spelling |
Understanding Carbohydrate Metabolism and Insulin Resistance in Acute Intermittent PorphyriaSolares, IsabelJericó, DanielCórdoba, Karol MarcelaMorales Conejo, MontserratEna, JavierEnríquez De Salamanca Lorente, RafaelFontanellas, Antonio616.3Hepatic porphyriasAcute intermittent porphyriaFastingGlucose homeostasisInsulin resistanceMitochondrial function and biogenesisMedicinaEndocrinologíaGastroenterología y hepatologíaMedicina interna32 Ciencias Médicas3205.02 Endocrinología3205.03 Gastroenterología3205 Medicina InternaPorphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks associated with high production, accumulation and urinary excretion of heme precursors, δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). The estimated clinical penetrance for AIP is extremely low (<1%), therefore it is likely that other factors may play an important role in the predisposition to developing attacks. Fasting is a known triggering factor. Given the increased prevalence of insulin resistance in patients and the large urinary loss of succinyl-CoA to produce ALA and PBG, we explore the impact of reduced availability of energy metabolites in the severity of AIP pathophysiology. Classic studies found clinical improvement in patients affected by AIP associated with the administration of glucose and concomitant insulin secretion, or after hyperinsulinemia associated with diabetes. Molecular studies have confirmed that glucose and insulin administration induces a repressive effect on hepatic ALA Synthase, the first and regulatory step of the heme pathway. More recently, the insulin-mimicking α-lipoic acid has been shown to improve glucose metabolism and mitochondrial dysfunction in a hepatocyte cell line transfected with interfering RNA targeting PBGD. In AIP mice, preventive treatment with an experimental fusion protein of insulin and apolipoprotein A-I improved the disease by promoting fat mobilization in adipose tissue, increasing the metabolite bioavailability for the TCA cycle and inducing mitochondrial biogenesis in the liver. In this review, we analyze the possible mechanisms underlying abnormal hepatocellular carbohydrate homeostasis in AIP.MDPIUniversidad Complutense de Madrid20222022-12-2020222022-12-20journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/72333reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengInstituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII) PI18%2F00860 ENSAYO PRECLINICO CON ARN MENSAJERO PARA EL TRATAMIENTO ETIOLOGICO DE LA PORFIRIA AGUDA INTERMITENTE. EFICACIA Y SEGURIDAD EN PRIMATES NO HUMANOS Y EN UN NUEVO MODELO DE PORFIRIA HEPATICA EN CONEJO .Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI21%2F00546 EVALUACION DE MEDICAMENTOS INNOVADORES BASADOS EN ARN EN LA CORRECCION DE LAS VIAS METABÓLICAS DE HEMO, GLICOLIPIDOS Y HOMOCISTEINA EN PACIENTES CON PORFIRIA AGUDA INTERMITENTE Y MODELOS EXPERIMENTALES DE RATÓN Y PRIMATES-NO-HUMANOS.open accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/723332026-06-02T12:44:21Z |
| dc.title.none.fl_str_mv |
Understanding Carbohydrate Metabolism and Insulin Resistance in Acute Intermittent Porphyria |
| title |
Understanding Carbohydrate Metabolism and Insulin Resistance in Acute Intermittent Porphyria |
| spellingShingle |
Understanding Carbohydrate Metabolism and Insulin Resistance in Acute Intermittent Porphyria Solares, Isabel 616.3 Hepatic porphyrias Acute intermittent porphyria Fasting Glucose homeostasis Insulin resistance Mitochondrial function and biogenesis Medicina Endocrinología Gastroenterología y hepatología Medicina interna 32 Ciencias Médicas 3205.02 Endocrinología 3205.03 Gastroenterología 3205 Medicina Interna |
| title_short |
Understanding Carbohydrate Metabolism and Insulin Resistance in Acute Intermittent Porphyria |
| title_full |
Understanding Carbohydrate Metabolism and Insulin Resistance in Acute Intermittent Porphyria |
| title_fullStr |
Understanding Carbohydrate Metabolism and Insulin Resistance in Acute Intermittent Porphyria |
| title_full_unstemmed |
Understanding Carbohydrate Metabolism and Insulin Resistance in Acute Intermittent Porphyria |
| title_sort |
Understanding Carbohydrate Metabolism and Insulin Resistance in Acute Intermittent Porphyria |
| dc.creator.none.fl_str_mv |
Solares, Isabel Jericó, Daniel Córdoba, Karol Marcela Morales Conejo, Montserrat Ena, Javier Enríquez De Salamanca Lorente, Rafael Fontanellas, Antonio |
| author |
Solares, Isabel |
| author_facet |
Solares, Isabel Jericó, Daniel Córdoba, Karol Marcela Morales Conejo, Montserrat Ena, Javier Enríquez De Salamanca Lorente, Rafael Fontanellas, Antonio |
| author_role |
author |
| author2 |
Jericó, Daniel Córdoba, Karol Marcela Morales Conejo, Montserrat Ena, Javier Enríquez De Salamanca Lorente, Rafael Fontanellas, Antonio |
| author2_role |
author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidad Complutense de Madrid |
| dc.subject.none.fl_str_mv |
616.3 Hepatic porphyrias Acute intermittent porphyria Fasting Glucose homeostasis Insulin resistance Mitochondrial function and biogenesis Medicina Endocrinología Gastroenterología y hepatología Medicina interna 32 Ciencias Médicas 3205.02 Endocrinología 3205.03 Gastroenterología 3205 Medicina Interna |
| topic |
616.3 Hepatic porphyrias Acute intermittent porphyria Fasting Glucose homeostasis Insulin resistance Mitochondrial function and biogenesis Medicina Endocrinología Gastroenterología y hepatología Medicina interna 32 Ciencias Médicas 3205.02 Endocrinología 3205.03 Gastroenterología 3205 Medicina Interna |
| description |
Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks associated with high production, accumulation and urinary excretion of heme precursors, δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). The estimated clinical penetrance for AIP is extremely low (<1%), therefore it is likely that other factors may play an important role in the predisposition to developing attacks. Fasting is a known triggering factor. Given the increased prevalence of insulin resistance in patients and the large urinary loss of succinyl-CoA to produce ALA and PBG, we explore the impact of reduced availability of energy metabolites in the severity of AIP pathophysiology. Classic studies found clinical improvement in patients affected by AIP associated with the administration of glucose and concomitant insulin secretion, or after hyperinsulinemia associated with diabetes. Molecular studies have confirmed that glucose and insulin administration induces a repressive effect on hepatic ALA Synthase, the first and regulatory step of the heme pathway. More recently, the insulin-mimicking α-lipoic acid has been shown to improve glucose metabolism and mitochondrial dysfunction in a hepatocyte cell line transfected with interfering RNA targeting PBGD. In AIP mice, preventive treatment with an experimental fusion protein of insulin and apolipoprotein A-I improved the disease by promoting fat mobilization in adipose tissue, increasing the metabolite bioavailability for the TCA cycle and inducing mitochondrial biogenesis in the liver. In this review, we analyze the possible mechanisms underlying abnormal hepatocellular carbohydrate homeostasis in AIP. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022-12-20 2022 2022-12-20 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/20.500.14352/72333 |
| url |
https://hdl.handle.net/20.500.14352/72333 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII) PI18%2F00860 ENSAYO PRECLINICO CON ARN MENSAJERO PARA EL TRATAMIENTO ETIOLOGICO DE LA PORFIRIA AGUDA INTERMITENTE. EFICACIA Y SEGURIDAD EN PRIMATES NO HUMANOS Y EN UN NUEVO MODELO DE PORFIRIA HEPATICA EN CONEJO . Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI21%2F00546 EVALUACION DE MEDICAMENTOS INNOVADORES BASADOS EN ARN EN LA CORRECCION DE LAS VIAS METABÓLICAS DE HEMO, GLICOLIPIDOS Y HOMOCISTEINA EN PACIENTES CON PORFIRIA AGUDA INTERMITENTE Y MODELOS EXPERIMENTALES DE RATÓN Y PRIMATES-NO-HUMANOS. |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Atribución 3.0 España https://creativecommons.org/licenses/by/3.0/es/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Atribución 3.0 España https://creativecommons.org/licenses/by/3.0/es/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
MDPI |
| publisher.none.fl_str_mv |
MDPI |
| dc.source.none.fl_str_mv |
reponame:Docta Complutense instname:Universidad Complutense de Madrid (UCM) |
| instname_str |
Universidad Complutense de Madrid (UCM) |
| reponame_str |
Docta Complutense |
| collection |
Docta Complutense |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869421203395969024 |
| score |
15,301603 |