ABSTRACT
The role of integrins, in particular αv integrins, in regulating insulin resistance is incompletely understood. We have previously shown that the αvß5 integrin ligand milk fat globule epidermal growth factor like 8 (MFGE8) regulates cellular uptake of fatty acids. In this work, we evaluated the impact of MFGE8 on glucose homeostasis. We show that acute blockade of the MFGE8/ß5 pathway enhances while acute augmentation dampens insulin-stimulated glucose uptake. Moreover, we find that insulin itself induces cell-surface enrichment of MFGE8 in skeletal muscle, which then promotes interaction between the αvß5 integrin and the insulin receptor leading to dampening of skeletal-muscle insulin receptor signaling. Blockade of the MFGE8/ß5 pathway also enhances hepatic insulin sensitivity. Our work identifies an autoregulatory mechanism by which insulin-stimulated signaling through its cognate receptor is terminated through up-regulation of MFGE8 and its consequent interaction with the αvß5 integrin, thereby establishing a pathway that can potentially be targeted to improve insulin sensitivity.
Subject(s)
Antigens, Surface/genetics , Insulin Resistance/genetics , Insulin/genetics , Milk Proteins/genetics , Receptors, Vitronectin/genetics , Animals , Antigens, CD/genetics , Fatty Acids/genetics , Fatty Acids/metabolism , Glucose/metabolism , Glycolipids/genetics , Glycoproteins/genetics , Homeostasis/genetics , Humans , Integrin alphaVbeta3/genetics , Lipid Droplets , Mice , Muscle, Skeletal/metabolism , Receptor, Insulin/genetics , Signal Transduction/geneticsABSTRACT
Endoscopic bariatric therapies can provide treatment options for obesity in non-surgical candidates, as a part of combination or serial treatment plans, and for the reduction of obesity-related comorbidities. Several complications of intragastric balloons have been documented, but spontaneous hyperinflation is a risk that has not been well reported previously. We describe two cases of spontaneous intragastric balloon hyperinflation and their outcomes.
Subject(s)
Gastric Balloon , Obesity, Morbid , Humans , Gastric Balloon/adverse effects , Female , Obesity, Morbid/surgery , Obesity, Morbid/complications , Obesity, Morbid/physiopathology , Adult , Treatment Outcome , Middle Aged , Male , Weight LossABSTRACT
Endoscopic ultrasound-guided tissue acquisition is now an imperative technique for the diagnosis of multiple diseases in the gastrointestinal tract and nearby structures. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and fine needle biopsy via dedicated FNB needles (EUS-FNB) are two standard-essential tools for tissue acquisition. The choice of needle type is an important factor determining appropriate tissue acquisition. Multiple studies have compared EUS-FNA versus EUS-FNB on different lesions also there are several studies evaluated different needles in terms of sampling adequacy and cytological and histological accuracy. Prior studies comparing prior-generation FNB needles to FNA did not show an increased diagnostic yield with FNB. However, the newer-generation needles have demonstrated enhanced performance compared with their predecessors. As they may provide a large amount of tissue for the cytological and histological evaluation, rapid onsite specimen evaluation (ROSE), and immunohistochemical and molecular analyses, which may be very important for targeted therapy. In this review, we discuss current evidence and literature on the use of the newer generation needles for pancreatic and non-pancreatic lesions.