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Bioorganic Chemistry Nov 2023Peptide YY (PYY) is a gastrointestinal hormone consisting of 36 amino acids, that is predominantly secreted by intestinal l-cells. Originally extracted from pig... (Review)
Review
Peptide YY (PYY) is a gastrointestinal hormone consisting of 36 amino acids, that is predominantly secreted by intestinal l-cells. Originally extracted from pig intestines, it belongs to the pancreatic polypeptide (PP) family, but has functions distinct from those of PP and neuropeptide Y (NPY). PYY is a potential treatment for type 2 diabetes mellitus (T2DM) because of its ability to delay gastric emptying, reduce appetite, decrease weight, and lower blood glucose. However, the clinical use of PYY is limited because it is rapidly cleared by the kidneys and degraded by enzymes. In recent years, researchers have conducted various structural modifications, including amino acid substitution, PEGylation, lipidation, and fusion of PYY with other proteins to prolong its half-life and enhance its biological activity. This study presents an overview of the recent progress on PYY, including its physiological functions, metabolites and structure-activity relationships.
Topics: Animals; Swine; Peptide YY; Diabetes Mellitus, Type 2; Obesity; Amino Acid Substitution; Amino Acids
PubMed: 37666110
DOI: 10.1016/j.bioorg.2023.106808 -
Journal of Clinical Medicine Jul 2023Pancreatic fistulas are highly feared complications following surgery on or near the pancreas, abdominal trauma, or severe inflammation. These fistulas arise from leaks... (Review)
Review
Pancreatic fistulas are highly feared complications following surgery on or near the pancreas, abdominal trauma, or severe inflammation. These fistulas arise from leaks in the pancreatic ductal system, leading to various complications such as abscesses, delayed gastric emptying, and hemorrhage. Severe cases present with sepsis or organ failure, dramatically increasing mortality and morbidity. Risk factors include smoking, high BMI, male gender, age, and surgery-related factors like prolonged operation time and non-ligation of the main pancreatic duct. Therefore, treatment options and preventive measurements have become a hot topic in recent years. Studies have investigated the use of fibrin sealants, different closure methods, and less invasive surgical techniques. Treatment options consist of conservative measurements and the use of percutaneous drainage, prophylactic transpapillary stenting, and surgery in severe cases. As EUS has become widely available, transmural stenting started to influence the management of pancreatic fluid collections (PFCs). However, studies on its use for the management of pancreatic fistulas are lacking. Medical treatment options like somatostatin analogs and pasireotide have been investigated but yielded mixed results.
PubMed: 37568446
DOI: 10.3390/jcm12155046 -
Metabolites Dec 2023Advances in high-throughput DNA sequencing have propelled research into the human microbiome and its link to metabolic health. We explore microbiome analysis methods,... (Review)
Review
Advances in high-throughput DNA sequencing have propelled research into the human microbiome and its link to metabolic health. We explore microbiome analysis methods, specifically emphasizing metabolomics, how dietary choices impact the production of microbial metabolites, providing an overview of studies examining the connection between enterotypes and diet, and thus, improvement of personalized dietary recommendations. Acetate, propionate, and butyrate constitute more than 95% of the collective pool of short-chain fatty acids. Conflicting data on acetate's effects may result from its dynamic signaling, which can vary depending on physiological conditions and metabolic phenotypes. Human studies suggest that propionate has overall anti-obesity effects due to its well-documented chemistry, cellular signaling mechanisms, and various clinical benefits. Butyrate, similar to propionate, has the ability to reduce obesity by stimulating the release of appetite-suppressing hormones and promoting the synthesis of leptin. Tryptophan affects systemic hormone secretion, with indole stimulating the release of GLP-1, which impacts insulin secretion, appetite suppression, and gastric emptying. Bile acids, synthesized from cholesterol in the liver and subsequently modified by gut bacteria, play an essential role in the digestion and absorption of dietary fats and fat-soluble vitamins, but they also interact directly with intestinal microbiota and their metabolites. One study using statistical methods identified primarily two groupings of enterotypes and . The -dominated enterotype, P-type, in humans correlates with vegetarians, high-fiber and carbohydrate-rich diets, and traditional diets. Conversely, individuals who consume diets rich in animal fats and proteins, typical in Western-style diets, often exhibit the Bacteroides-dominated, B-type, enterotype. The P-type showcases efficient hydrolytic enzymes for plant fiber degradation but has limited lipid and protein fermentation capacity. Conversely, the B-type features specialized enzymes tailored for the degradation of animal-derived carbohydrates and proteins, showcasing an enhanced saccharolytic and proteolytic potential. Generally, models excel at predictions but often struggle to fully elucidate why certain substances yield varied responses. These studies provide valuable insights into the potential for personalized dietary recommendations based on enterotypes.
PubMed: 38132864
DOI: 10.3390/metabo13121182 -
British Journal of Pharmacology Apr 2024The objective is to review the newer pharmacological interventions for obesity, specifically single, dual and triple incretin receptor agonists that are either available... (Review)
Review
The objective is to review the newer pharmacological interventions for obesity, specifically single, dual and triple incretin receptor agonists that are either available or in the pipeline for treatment of obesity. The three incretin receptor targets are glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and glucagon. There are several approved single or dual incretin agonists which can be administered subcutaneously daily (e.g., liraglutide) or weekly (e.g., semaglutide, dulaglutide, and exenatide QW), and other experimental dual or triple incretin agonists. Analogues of amylin, peptide YY and oxyntomodulin, as well as the combination of a GLP1R agonist and GIPR antagonist also are in development. Oral semaglutide (administered daily) is approved for type 2 diabetes mellitus and is on track for regulatory review for obesity. The review includes specifically perspectives on the effects of these mechanisms and pharmacological agents on gastric emptying, which contribute to satiation and weight loss, in addition to the established evidence on effects on central mechanisms controlling appetite. In the future, it is anticipated that small molecule GLP-1 receptor agonists (e.g., oral danuglipron) will be developed for treating obesity. These pharmacological agents are having significant impact on glycaemic control and obesity and on their co-morbidities.
Topics: Humans; Incretins; Diabetes Mellitus, Type 2; Obesity; Glucagon-Like Peptide 1; Gastric Inhibitory Polypeptide; Hypoglycemic Agents; Glucagon-Like Peptide-1 Receptor
PubMed: 37917871
DOI: 10.1111/bph.16278 -
Gut Nov 2023Symptoms in gastroparesis (Gp) and functional dyspepsia (FD) overlap; using egg protein substitute to measure gastric emptying of solids (GES), ~40% of patients are... (Clinical Trial)
Clinical Trial
OBJECTIVE
Symptoms in gastroparesis (Gp) and functional dyspepsia (FD) overlap; using egg protein substitute to measure gastric emptying of solids (GES), ~40% of patients are reclassified from Gp to FD, and vice versa. Our aim was to assess inter-individual and intra-individual coefficients of variation (COV) in GES in symptomatic patients with Gp or FD with documented slow or normal GES, respectively.
DESIGN
Scintigraphic GES (T and GE% at 2 and 4 hours) using a 320 kcal real egg meal (30% fat) was tested in the following: single measurements in 20 patients with diabetes mellitus (10 each type 1 and type 2); repeat GES to estimate COV measured: 3 days apart in 9 Gp, 4 weeks apart in 21 Gp and 18 with FD with normal GE assigned to placebo and in 70 patients at 94.3 weeks (median) apart.
RESULTS
COV for GE% at 4 hours and GE T were respectively 14.2% and 23.5% in FD and 27.5% and 33% in Gp; COV for GE% at 4 hours and GE T up to 4 weeks apart were 23.4% and 37.9% in FD and 20.1% and 33% in Gp. GE% at 2 hours showed less consistent results. However, >85% retained original diagnosis as normal or delayed. From clinical GES to baseline research for Gp group, repeat GES (after treatment) showed the COV for GE% at 4 hours was 37.3% at median 94.3 weeks, with 26/70 changed diagnoses.
CONCLUSION
The 320 kcal (30% fat) GES scintigraphic test provides consistent diagnosis in >85% and should be the standard test for suspected gastric emptying disorders.
Topics: Humans; Diabetes Mellitus; Dyspepsia; Gastric Emptying; Gastroparesis; Radionuclide Imaging
PubMed: 37726164
DOI: 10.1136/gutjnl-2023-330733 -
Frontiers in Bioscience (Landmark... Nov 2023Glucagon-like peptide-1 (GLP-1), an incretin hormone primarily secreted by intestinal L cells, regulates glucose metabolism by increasing insulin synthesis and... (Review)
Review
Glucagon-like peptide-1 (GLP-1), an incretin hormone primarily secreted by intestinal L cells, regulates glucose metabolism by increasing insulin synthesis and secretion, decreasing plasma glucagon levels, reducing food intake, and slowing gastric emptying. This has led to the development of GLP-1 receptor (GLP-1R) agonists as a treatment for diabetes and obesity. In addition to being present in beta cells, GLP-1R has also been identified in blood vessels and the heart, suggesting that GLP-1R agonists may have an impact on cardiovascular health. There is now substantial evidence supporting GLP-1's protective effects on the cardiovascular system. This review summarizes the current research on GLP-1-based therapy for coronary artery disease (CAD) by examining its protective effects against inflammation and ischemia/reperfusion injury and analyzing clinical trials on GLP-1-based therapies for CAD. Although results from various studies were inconsistent, the challenge of transitioning GLP-1-based therapies from the laboratory to the clinical setting remains. Further well-designed and high-quality studies are necessary to determine the efficacy and safety of GLP-1 for patients with CAD.
Topics: Humans; Glucagon-Like Peptide 1; Coronary Artery Disease; Diabetes Mellitus, Type 2; Incretins; Cardiovascular System
PubMed: 38062835
DOI: 10.31083/j.fbl2811315 -
Journal of Gastroenterology and... Nov 2023Low-intensity pulsed ultrasound (LIPUS) can effectively regulate the central and peripheral nervous system. However, whether LIPUS could act on acupuncture points to...
BACKGROUND AND AIM
Low-intensity pulsed ultrasound (LIPUS) can effectively regulate the central and peripheral nervous system. However, whether LIPUS could act on acupuncture points to modulate the activity of peripheral nervous has rarely been studied. Our study aimed to investigate whether LIPUS at ST36 could improve gastric emptying in diabetic gastroparesis rats.
METHODS
Sprague-Dawley male rats were divided into three groups: control group (CON), diabetic gastroparesis group (DM), and diabetic gastroparesis LIPUS treated group (LIPUS). The body weight and blood glucose were recorded every week. Glucose tolerance, gastric emptying rate, and gastric motility were measured before and after treatment. Gastric motility was assessed by ultrasonic examination and Muscle strip experiment. The expression level of c-Kit was assessed by immunohistochemistry staining. Levels of TNF-α, p-NF-κB p-65, NF-κB p-65, and p-IKKβ, IKKβ were measured by western blot.
RESULTS
We reported LIPUS at an intensity of 0.88 W/cm exhibited significant differences in functional recovery of gastric delayed emptying in diabetic rats. Through ultrasound gastric motility functional testing and analysis of gastric antral smooth muscle strips indirectly and directly proved the effectiveness of LIPUS for the recovery of gastric delayed emptying. Pathological analysis and western blot indicated that the mechanism by which LIPUS applied to ST36 improved gastric motility may be partially attributed to the inhibition of the TNF-α/IKKβ/NF-κB signaling pathway, thereby rescuing the damaged interstitial cells of Cajal network.
CONCLUSION
LIPUS at ST36 improved the gastric motility and rescued the damaged networks of interstitial cells of Cajal. LIPUS may have a promising therapeutic potential for diabetic gastroparesis.
Topics: Rats; Male; Animals; NF-kappa B; Gastroparesis; I-kappa B Kinase; Tumor Necrosis Factor-alpha; Rats, Sprague-Dawley; Diabetes Mellitus, Experimental; Signal Transduction; Ultrasonic Waves; Protein Serine-Threonine Kinases
PubMed: 37581362
DOI: 10.1111/jgh.16321 -
Life (Basel, Switzerland) Aug 2023Gastroparesis (GP) is a chronic disease characterized by upper gastrointestinal symptoms, primarily nausea and vomiting, and delayed gastric emptying (GE), in the... (Review)
Review
Gastroparesis (GP) is a chronic disease characterized by upper gastrointestinal symptoms, primarily nausea and vomiting, and delayed gastric emptying (GE), in the absence of mechanical GI obstruction. The underlying pathophysiology of GP remains unclear, but factors contributing to the condition include vagal nerve dysfunction, impaired gastric fundic accommodation, antral hypomotility, gastric dysrhythmias, and pyloric dysfunction. Currently, gastric emptying scintigraphy (GES) is considered the gold standard for GP diagnosis. However, the overall delay in GE weakly correlates with GP symptoms and their severity. Recent research efforts have focused on developing treatments that address the presumed underlying pathophysiological mechanisms of GP, such as pyloric hypertonicity, with Gastric Peroral Endoscopic Myotomy (G-POEM) one of these procedures. New promising diagnostic tools for gastroparesis include wireless motility capsule (WMC), the 13 carbon-GE breath test, high-resolution electrogastrography, and the Endoluminal Functional Lumen Imaging Probe (EndoFLIP). Some of these tools assess alterations beyond GE, such as muscular electrical activity and pyloric tone. These modalities have the potential to characterize the pathophysiology of gastroparesis, identifying patients who may benefit from targeted therapies. The aim of this review is to provide an overview of the current knowledge on diagnostic pathways in GP, with a focus on the association between diagnosis, symptoms, and treatment.
PubMed: 37629600
DOI: 10.3390/life13081743 -
Journal of Neurology Nov 2023Multiple system atrophy (MSA) is a sporadic, fatal, and rapidly progressive neurodegenerative disease of unknown etiology that is clinically characterized by autonomic... (Review)
Review
Multiple system atrophy (MSA) is a sporadic, fatal, and rapidly progressive neurodegenerative disease of unknown etiology that is clinically characterized by autonomic failure, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination. Early onset and extensive autonomic dysfunction, including cardiovascular dysfunction characterized by orthostatic hypotension (OH) and supine hypertension, urinary dysfunction characterized by overactive bladder and incomplete bladder emptying, sexual dysfunction characterized by sexual desire deficiency and erectile dysfunction, and gastrointestinal dysfunction characterized by delayed gastric emptying and constipation, are the main features of MSA. Autonomic dysfunction greatly reduces quality of life and increases mortality. Therefore, early diagnosis and intervention are urgently needed to benefit MSA patients. In this review, we aim to discuss the systematic treatment of autonomic dysfunction in MSA, and focus on the current methods, starting from non-pharmacological methods, such as patient education, psychotherapy, diet change, surgery, and neuromodulation, to various drug treatments targeting autonomic nerve and its projection fibers. In addition, we also draw attention to the interactions among various treatments, and introduce novel methods proposed in recent years, such as gene therapy, stem cell therapy, and neural prosthesis implantation. Furthermore, we elaborate on the specific targets and mechanisms of action of various drugs. We would like to call for large-scale research to determine the efficacy of these methods in the future. Finally, we point out that studies on the pathogenesis of MSA and pathophysiological mechanisms of various autonomic dysfunction would also contribute to the development of new promising treatments and concepts.
Topics: Male; Humans; Multiple System Atrophy; Quality of Life; Autonomic Nervous System Diseases; Erectile Dysfunction; Parkinsonian Disorders
PubMed: 37477834
DOI: 10.1007/s00415-023-11876-y -
Appetite Oct 2023Older adults are advised to increase their protein intake to maintain their muscle mass. However, protein is considered the most satiating macronutrient and this... (Randomized Controlled Trial)
Randomized Controlled Trial
Older adults are advised to increase their protein intake to maintain their muscle mass. However, protein is considered the most satiating macronutrient and this recommendation may cause a decrease in total energy intake. To date, satiety studies comparing all three macronutrients have been undertaken in young adults, and it is unclear if the same response is seen in older adults. The objective of this study was to compare the effect of preloads high in protein, fat, and carbohydrate but equal in energy (∼300 kcal) and volume (250 ml) on energy intake, perceived appetite, and gastric emptying in younger and older adults. Twenty older and 20 younger adults completed a single-blinded randomised crossover trial involving three study visits. Participants consumed a standard breakfast, followed by a preload milkshake high in either carbohydrate, fat, or protein. Three hours after the preload, participants were offered an ad libitum meal to assess food intake. Visual analogue scales were used to measure perceived appetite and gastric emptying was measured via the C-octanoic acid breath test. There was no significant effect of preload type or age on energy intake either at the ad libitum meal, self-recorded food intake for the rest of the test day or subjective appetite ratings. There was a significant effect of preload type on gastric emptying latency phase and ascension time, and an effect of age on gastric emptying latency and lag phase such that older adults had faster emptying. In conclusion, energy intake, and perceived appetite were not affected by macronutrient content of the preloads in both younger and older adults, but gastric emptying times differed.
Topics: Young Adult; Humans; Aged; Satiation; Appetite; Energy Intake; Nutrients; Eating; Carbohydrates; Cross-Over Studies
PubMed: 37507052
DOI: 10.1016/j.appet.2023.106982