Author Interviews, Diabetes, Gastrointestinal Disease / 04.05.2023
DDW23: Endoscopic ReCET Procedure Plus Semaglutide Eliminates Need for Insulin in Type 2 Diabetes
MedicalResearch.com Interview with:
Celine B. E. Busch, Research Associate
Gastroenterology and Hepatology Standard PhD Candidate
Dr. Jacques Bergman
Professor, Gastroenterology and Hepatology
Amsterdam UMC
MedicalResearch.com: What is the background for this study? Would you describe the ReCET procedure?
Response: Currently more than 400 million people worldwide have type 2 diabetes (T2D) and these numbers are rapidly increasing. At the moment there is no treatment option available that effectively treats the root cause of T2D, i.e. insulin resistance, the increasing loss of response to our body’s own insulin. T2D is generally treated with drug therapy, yet drug therapy can be expensive, requires the patient to take their drugs every day, and at best “controls” the disease without actually resolving it. Despite the availability of many T2D drugs, less than 50% of all T2D have adequately controlled blood glucose levels.
The duodenum (the first part of the small bowel, immediately distal to the stomach) has proven to play a crucial role in glucose homeostasis in T2D. We know from bariatric surgery, that bypassing the duodenum by an Roux-en-Y Gastric Bypass has an immediate and profound effect on T2D by improving the sensitivity to the body’s own insulin resistance. However, performing invasive bariatric surgery for many T2D is not feasible. But we can reach the duodenum easily via upper GI endoscopy.
ReCET is a single endoscopic procedure, performed under deep sedation. The ReCET catheter is advanced next to the scope, and once it is placed in the duodenum the flex circuit is unfolded until it touches the full circumference of the duodenum. The flex circuit contains the electrodes that create a pulsed electric field which “electroporates” the cells. Electroporation irreversibly makes small, that cause the cell to die of natural cell death, or apoptosis. This process can be precisely titrated for its depth of damage and does not generate heat thus avoiding damage to deeper wall layers, a major hurdle for standard endoscopic ablation techniques. The ReCET procedure lasts about 60 minutes to treat a 10-15 cm segment of the duodenum. The procedure does not cause significant side-effects and patients are discharged the same day.
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Response: We were broadly interested in discovering instances of bacterial genes that have been acquired by diverse animal genomes over millions of years of evolution by the process of horizontal gene transfer (HGT). Since these events are quite rare and most previous discoveries have been serendipitous, we developed computational methods to identify genes acquired by HGT in animals. One of the exciting discoveries from our work was that vertebrate IRBP appeared to have originated in bacteria and is now a critical component of the vertebrate visual cycle, so this paper focuses on that one discovery.
IRBP or interphotoreceptor retinoid binding protein is an important protein present in the space between two major cell types in our eyes, photoreceptor cells and RPE cells. Our ability to see involves an intricate set of steps where light is first sensed by causing a change (isomerization) in the chemical structure of molecules in the eye called retinoids. This sensing of light occurs in our photoreceptor cells. Following this change in the chemical structure, the retinoid needs to be recycled back to the chemical structure that can again sense light. This recycling occurs in RPE cells. IRBP performs the essential function of shuttling retinoids between the photoreceptors and the RPE cells, which allows the cycle of sensing and regeneration to work. Supporting its importance, mutations in IRBP (also known as retinol binding protein 3 or RBP3) can cause several severe human eye diseases.
Larissa K. Samuelson, PhD
Professor
Developmental Dynamics Lab
School of Psychology; UK 14th for Research Quality
Psychology, Psychiatry, and Neuroscience
University of East Anglia, United Kingdom
MedicalResearch.com: What is the background for this study?
Response: Words direct the attention of infants, children and adults to mentioned objects in the environment. When someone says “Can you find the candy,” you look to the candy sitting on the counter. This fact is the basis of many tests of infant cognition in laboratories. To find out if a child knows the word “bike” we put a picture of a bike and a truck on a TV screen, say the word “bike” and see if they look at the correct object.
There is also evidence that words can direct attention even if you don’t know what they mean yet. For example, in studies of learning in the lab novel made up words like “modi” can direct children’s attention to specific features of objects. One particular example of this is the “shape bias”. If a two-year-old is shown a novel object and told a novel name, for example “This is my blicket,” and then asked, “Can you get your blicket” and shown one object that matches the named one in shape and another that is made from the same material, they will attend to the one that matches in shape. Researchers think the naming event “This is my…” cues children to look at things that are the same shape because they already know many names for things in sets that are similar in shape; cups are all cup-shaped, keys are all key-shaped, spoons are all spoon-shaped, etc.
Prior research suggests there may be differences in the way children who struggle with language decide what a new word means. For example, children with Developmental Language Disorder do not pay attention to the same things when learning new words as children with typical language development. These children do not look to an object that matches a named exemplar in shape when asked to “get your blicket”. But you can’t diagnose children with DLD until they are 3 or 4. We want to see if we can identify these children earlier, so they can get early support.
