A lower duodenal immune response is associated with an increase of insulin resistance in patients with morbid obesity

Ho-Plágaro, Ailec; Santiago‐Fernández, Concepción; García‐Serrano, Sara; Rodriguez, Cristina; Garrido‐Sánchez, Lourdes; Escamilla, Alejandro; Gonzalo, Montserrat; Montiel-Casado, Custodia; Alcaín‐Martínez, Guillermo; García‐Muñoz, B.; Ruiz-Santana, Natalia; Vázquez‐Pedreño, Luis; Garcı́a-Fuentes, Eduardo

doi:10.1038/s41366-019-0458-1

Cited by 8 publications

(16 citation statements)

References 43 publications

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“…Previous studies have shown the involvement of insulin resistance in the intestinal metabolism dysregulation [4]. However, changes in the human intestinal metabolism in insulin resistance and/or type 2 diabetes mellitus (T2DM) have not been explored in depth [3,[5][6][7]. Intestinal glucose-6 phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase-cytosolic form (PEPCK-c), which are involved in the gluconeogenesis pathway and in the control of endogenous glucose production [8], are targets of insulin [9].…”

Section: Introductionmentioning

confidence: 99%

Jejunal Insulin Signalling Is Increased in Morbidly Obese Subjects with High Insulin Resistance and Is Regulated by Insulin and Leptin

Gutiérrez-Repiso

Ho-Plágaro

Santiago‐Fernández

et al. 2020

JCM

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Little is known about the jejunal insulin signalling pathways in insulin resistance/diabetes states and their possible regulation by insulin/leptin. We study in jejunum the relation between insulin signalling and insulin resistance in morbidly obese subjects with low (MO-low-IR) or with high insulin resistance (MO-high-IR), and with type 2 diabetes treated with metformin (MO-metf-T2DM), and the effect of insulin/leptin on intestinal epithelial cells (IEC). Insulin receptor substrate-1 (IRS1) and the catalytic p110β subunit (p110β) of phosphatidylinositol 3-kinase (PI3K) were higher in MO-high-IR than in MO-low-IR. The regulatory p85α subunit of PI3K (p85α)/p110β ratio was lower in MO-high-IR and MO-metf-T2DM than in MO-low-IR. Akt-phosphorylation in Ser473 was reduced in MO-high-IR compared with MO-low-IR. IRS1 and p110-β were associated with insulin and leptin levels. The improvement of body mass index (BMI) and HOMA-IR (homeostasis model assessment of insulin resistance index) after bariatric surgery was associated with a higher IRS1 and a lower p85α/p110β ratio. IEC (intestinal epithelial cells) incubation with a high glucose + insulin dose produced an increase of p85α and p110β. High dose of leptin produced an increase of IRS1, p85α and p110β. In conclusion, despite the existence of insulin resistance, the jejunal expression of genes involved in insulin signalling was increased in MO-high-IR. Their expressions were regulated mainly by leptin. IRS1 and p85α/p110β ratio was associated with the evolution of insulin resistance after bariatric surgery.

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Section: Introductionmentioning

confidence: 99%

Jejunal Insulin Signalling Is Increased in Morbidly Obese Subjects with High Insulin Resistance and Is Regulated by Insulin and Leptin

Gutiérrez-Repiso

Ho-Plágaro

Santiago‐Fernández

et al. 2020

JCM

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“…Functional analysis and the KEGG pathway mapping tool showed functions mainly related to antimicrobial and immune response, cancer, diabetes, xenobiotic metabolism, maintenance of gastrointestinal epithelium, digestion, and lipid metabolism. In a previous study, we showed that insulin resistance was associated with a decrease of the duodenal proteins (cytokines and chemokines) involved in the immune response (9). However, there have been few studies in human duodenum analyzing the association between inflammation and T2DM.…”

Section: Discussionmentioning

confidence: 99%

“…OBESITY BIOLOGY AND INTEGRATED PHYSIOLOGY function is altered in obesity, at least in animal studies (8). Previously, in human duodenum we found a relationship between insulin resistance with the expression of pro-and anti-inflammatory cytokines and intestinal permeability (9). Likewise, the intestine of obese mice showed a disorganized distribution of cell junctions and increased intestinal permeability (10).…”

Section: Original Articlementioning

confidence: 98%

“…One month before sleeve gastrectomy, they underwent programmed gastroscopy to exclude alterations in the stomach, at which time duodenal biopsies were taken. The women with obesity were classified into two groups according to the homeostatic model assessment of insulin resistance (HOMA-IR) level: those with lower HOMA-IR value (< 4.7) ("MO-lower-IR") and those with higher HOMA-IR value (> 4.7) ("MO-higher-IR") (both groups without treatment for T2DM) (9). The nonobese women were selected among those who underwent programmed gastroscopy at the Virgen de la Victoria University Hospital (Málaga, Spain) for a possible dysphagia and uncomplicated cases of acid reflux, with nonpathological results, at which time duodenal biopsies were taken.…”

Section: Patientsmentioning

confidence: 99%

“…Duodenal biopsies from nonobese women and women with obesity from the second part of the duodenum were obtained in the fasting state during the gastroscopy that the women underwent (9).…”

Section: Duodenal Samplesmentioning

confidence: 99%

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Different Expression of Duodenal Genes Related to Insulin Resistance Between Nonobese Women and Those with Severe Obesity

Ho-Plágaro

Santiago‐Fernández

Rodríguez‐Díaz

et al. 2020

Obesity

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Objective The study aim was to identify changes in duodenal gene expression associated with the development of insulin resistance according to the BMI of women. Methods Duodenal samples were assessed by microarray in four groups of women, nonobese women and women with severe obesity, with both low and high insulin resistance. Results There was a group of shared downregulated differentially expressed genes (DEGs) related to tissue homeostasis and antimicrobial humoral response in women with higher insulin resistance both with severe obesity and without obesity. In the exclusive DEGs found in severe obesity, downregulated DEGs related to the regulation of the defense response to bacterium and cell adhesion, involving pathways related to the immune system, inflammation, and xenobiotic metabolism, were observed. In the exclusive DEGs from nonobese women with higher insulin resistance, upregulated DEGs mainly related to the regulation of lipoprotein lipase activity, very low‐density lipoprotein particle remodeling, lipid metabolic process, antigen processing, and the presentation of peptide antigen were found. Conclusions Independent of BMI, higher insulin resistance was associated with a downregulation of duodenal DEGs mainly related to the immune system, inflammation, and xenobiotic metabolism. Also, intestinal lipoprotein metabolism may have a certain relevance in the regulation of insulin resistance in nonobese women.

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Biochemical and immunological changes in obesity

Barakat

Almeida

2021

Archives of Biochemistry and Biophysics

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A lower duodenal immune response is associated with an increase of insulin resistance in patients with morbid obesity

Cited by 8 publications

References 43 publications

Jejunal Insulin Signalling Is Increased in Morbidly Obese Subjects with High Insulin Resistance and Is Regulated by Insulin and Leptin

Jejunal Insulin Signalling Is Increased in Morbidly Obese Subjects with High Insulin Resistance and Is Regulated by Insulin and Leptin

Different Expression of Duodenal Genes Related to Insulin Resistance Between Nonobese Women and Those with Severe Obesity

Biochemical and immunological changes in obesity

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