title: Jejunal gluconeogenesis associated with insulin resistance level and its evolution after Roux-en-Y gastric bypass.
abstract: BACKGROUND
  Intestinal gluconeogenesis (GNG) may play an important role in glucose homeostasis, but there is little information about the condition in humans.
  
  
  OBJECTIVE
  To study the relationship between intestinal GNG and insulin resistance, its association with the evolution of morbidly obese patients after bariatric surgery, and the effect of insulin and or leptin.
  
  
  METHODS
  Regional university hospital, Malaga (Spain).
  
  
  METHODS
  Jejunal mRNA expression of genes involved in GNG was analyzed in 3 groups of morbidly obese patients who underwent Roux-en-Y gastric bypass: with low insulin resistance (MO-low-IR), with high insulin resistance (MO-high-IR), and with type 2 diabetes treated with metformin (MO-metf-T2D). Also, intestinal epithelial cells (IEC) from MO-low-IR were incubated with different doses of insulin and or leptin.
  
  
  RESULTS
  In MO-high-IR, glutaminase, phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6 Pase), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 α), and sterol regulatory element-binding proteins 1 c (SREBP-1 c) expressions were significantly higher than in MO-low-IR. In MO-metf-T2 D, only PEPCK was significantly lower than in MO-high-IR. In IEC, an incubation with a high glucose and insulin dose produced an increase of PEPCK and SREBP-1 c, and a decrease of glutaminase, fructose 1,6-bisphosphatase (FBPase), and PGC-1 α expression. At high doses of leptin, G6 Pase and FBPase were significantly increased. The improvement of insulin resistance 3 months after bariatric surgery was positively associated with high G6 Pase and FBPase expression.
  
  
  CONCLUSIONS
  mRNA expression of genes involved in GNG is increased in the jejunum of MO-high-IR, and regulated by insulin and or leptin. High mRNA expression of genes involved in GNG is associated with a better evolution of insulin resistance after bariatric surgery.
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga/Hospital Regional Universitario, Málaga, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gutierrez-Repiso
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga/Hospital Regional Universitario, Málaga, Spain; CIBERDEM, Instituto de Salud Carlos III, Málaga, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Garcia-Serrano
authors.affiliation: Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Instituto de Investigación Biomédica de Málaga/Hospital Regional Universitario, Málaga, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Moreno-Ruiz
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga/Hospital Clínico Virgen de la Victoria, Málaga, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Alcain-Martinez
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga/Hospital Regional Universitario, Málaga, Spain. Electronic address: paqui.endocrino@gmail.com.
authors.forename: Francisca
authors.initials: F
authors.lastname: Rodriguez-Pacheco
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga/Hospital Clínico Virgen de la Victoria, Málaga, Spain; CIBEROBN, Instituto de Salud Carlos III, Málaga, Spain. Electronic address: edugf1@gmail.com.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Garcia-Fuentes
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D015390:Gastric Bypass; D005786:Gene Expression Regulation; D005943:Gluconeogenesis / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007583:Jejunum / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D008297:Male; D009767:Obesity, Morbid / Q000150:complications / Q000378:metabolism / Q000601:surgery*; D011184:Postoperative Period; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013030:Spain; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger
keywords: Bariatric surgery; Gluconeogenesis; Insulin; Insulin resistance; Jejunum; Leptin; Metformin; Morbid obesity; Type 2 diabetes