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

2020 ◽  
Vol 9 (1) ◽  
pp. 196 ◽  
Author(s):  
Carolina Gutierrez-Repiso ◽  
Ailec Ho-Plagaro ◽  
Concepción Santiago-Fernandez ◽  
Sara Garcia-Serrano ◽  
Francisca Rodríguez-Pacheco ◽  
...  

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.

2021 ◽  
Vol 12 ◽  
Author(s):  
Alicja Maria Nogacka ◽  
Clara G. de los Reyes-Gavilán ◽  
Silvia Arboleya ◽  
Patricia Ruas-Madiedo ◽  
Ceferino Martínez-Faedo ◽  
...  

The intestinal microbiota plays important roles in the maintenance of health. Strategies aiming at its modulation, such as probiotics, have received a deal of attention. Several strains have been studied in different in vitro models; however, the correlation of results obtained with the in vivo data has been limited. This questions the usefulness of such in vitro selection models, traditionally relying on over-simplified tests, not considering the influence of the accompanying microbiota or focusing on microbiota composition without considering functional traits. Here we assess the potential of six Bifidobacterium, Lactobacillus and Lacticaseibacillus strains in an in vitro model to determine their impact on the microbiota not just in terms of composition but also of functionality. Moreover, we compared the responses obtained in two different population groups: normal-weight and severely obese subjects. Fecal cultures were conducted to evaluate the impact of the strains on specific intestinal microbial groups, on the production of short-chain fatty acids, and on two functional responses: the production of gas and the interaction with human intestinal epithelial cells. The response to the different probiotics differed between both human groups. The addition of the probiotic strains did not induce major changes on the microbiota composition, with significant increases detected almost exclusively for the species added. Higher levels of gas production were observed in cultures from normal-weight subjects than in the obese population, with some strains being able to significantly reduce gas production in the latter group. Moreover, in obese subjects all the Bifidobacterium strains tested and Lacticaseibacillus rhamnosus GG were able to modify the response of the intestinal cells, restoring values similar to those obtained with the microbiotas of normal-weight subjects. Our results underline the need for the screening and selection of probiotics in a target-population specific manner by using appropriate in vitro models before enrolling in clinical intervention trials.


2007 ◽  
Vol 92 (3) ◽  
pp. 1168-1171 ◽  
Author(s):  
Dominik G. Haider ◽  
Karin Schindler ◽  
Gerhard Prager ◽  
Arthur Bohdjalian ◽  
Anton Luger ◽  
...  

Abstract Context: Administration of retinol-binding protein 4 (RBP-4) impairs insulin sensitivity in animals, and elevated serum concentrations have been associated with insulin resistance in humans. Objective: We have studied whether weight loss influences RBP-4. Patients and Methods: Fasting serum concentrations of RBP-4 were measured before and 6 months after gastric banding surgery in 33 morbidly obese patients aged 40 ± 11 yr with a body mass index (BMI) of 46 ± 5 kg/m2. Fourteen healthy subjects aged 29 ± 5 yr with a BMI less than 25 kg/m2 served as controls. To characterize the association of weight loss with central and peripheral appetite regulation, the signaling protein agouti-related protein (AGRP), the orexigenic hormone ghrelin, and its recently identified antagonist obestatin were determined. Results: At baseline, RBP-4 levels were markedly higher in obese than in lean subjects (2.7 ± 0.5 vs. 0.9 ± 0.5 μg/ml; P < 0.001). In contrast, AGRP and obestatin were lower in obese subjects compared with lean controls (all P < 0.001). Six months after gastric banding, BMI was reduced to 40 ± 5 kg/m2, RBP-4 was reduced to 2.0 ± 0.7 μg/ml, AGRP increased from 1.8 ± 1.1 to 3.4 ± 1.1 ng/ml, ghrelin increased from 93 ± 58 to 131 ± 70 pg/ml, and obestatin increased from 131 ± 52 to 173 ± 35 pg/ml (all P < 0.05). Individual changes of RBP-4 were associated with changes of BMI (r = 0.72), the homeostasis model assessment insulin resistance-index (r = 0.53), and total cholesterol (r = 0.42, for all P < 0.05). Conclusion: Reductions in circulating RBP-4 may contribute to improved insulin resistance in morbidly obese subjects after weight loss. This is accompanied by favorable changes in appetite-regulating hormones, which might support the sustained weight loss after obesity surgery.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Akhila Mallipedhi ◽  
Sarah L. Prior ◽  
Gareth Dunseath ◽  
Richard M. Bracken ◽  
Jonathan Barry ◽  
...  

Aim. We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance.Methods. A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA).Results. Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r=0.55,P=0.01), HOMA-IR (r=0.61,P=0.009), and HOMA %S (r=-0.71,P=0.002). OEA was correlated with weight (r=0.49,P=0.03), waist circumference (r=0.52,P=0.02), fasting insulin (r=0.49,P=0.04), and HOMA-IR (r=0.48,P=0.05). PEA was correlated with fasting insulin (r=0.49,P=0.04). 2-AG had a negative correlation with fasting glucose (r=-0.59,P=0.04).Conclusion. Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis.


Author(s):  
Julian P. Heath ◽  
Buford L. Nichols ◽  
László G. Kömüves

The newborn pig intestine is adapted for the rapid and efficient absorption of nutrients from colostrum. In enterocytes, colostral proteins are taken up into an apical endocytotic complex of channels that transports them to target organelles or to the basal surface for release into the circulation. The apical endocytotic complex of tubules and vesicles clearly is a major intersection in the routes taken by vesicles trafficking to and from the Golgi, lysosomes, and the apical and basolateral cell surfaces.Jejunal tissues were taken from piglets suckled for up to 6 hours and prepared for electron microscopy and immunocytochemistry as previously described.


2001 ◽  
Vol 120 (5) ◽  
pp. A504-A504
Author(s):  
A NEUMANN ◽  
M DEPKAPRONDZINSKI ◽  
C WILHELM ◽  
K FELGENHAUER ◽  
T CASPRITZ ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document