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Molecular and Cellular Endocrinology Dec 2023The lining of our intestinal surface contains an array of hormone-producing cells that are collectively our bodies' largest endocrine cell reservoir. These...
The lining of our intestinal surface contains an array of hormone-producing cells that are collectively our bodies' largest endocrine cell reservoir. These "enteroendocrine" (EE) cells reside amongst the billions of absorptive epithelial and other cell types that line our gastrointestinal tract and can sense and respond to the ever-changing internal environment in our gut. EE cells release an array of important signalling molecules that can act as hormones, including glucagon-like peptide (GLP-1) and peptide YY (PYY) which are co-secreted from L cells. While much is known about the effects of these hormones on metabolism, insulin secretion and food intake, less is understood about their secretion from human intestinal tissue. In this study we assess whether GLP-1 and PYY release differs across human small and large intestinal tissue locations within the gastrointestinal tract, and/or by sex, body weight and the age of an individual. We identify that the release of both hormones is greater in more distal regions of the human colon, but is not different between sexes. We observe a negative correlation of GLP-1 and BMI in the small, but not large, intestine. Increased aging correlates with declining secretion of both GLP-1 and PYY in human large, but not small, intestine. When the data for large intestine is isolated by region, this relationship with age remains significant for GLP-1 in the ascending and descending colon and in the descending colon for PYY. This is the first demonstration that site-specific differences in GLP-1 and PYY release occur in human gut, as do site-specific relationships of L cell secretion with aging and body mass.
PubMed: 37739120
DOI: 10.1016/j.mce.2023.112072 -
International Journal of Molecular... May 2024Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of motor neurons. Emerging evidence suggests a potential...
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of motor neurons. Emerging evidence suggests a potential link between metabolic dysregulation and ALS pathogenesis. This study aimed to investigate the relationship between metabolic hormones and disease progression in ALS patients. A cross-sectional study was conducted involving 44 ALS patients recruited from a tertiary care center. Serum levels of insulin, total amylin, C-peptide, active ghrelin, GIP (gastric inhibitory peptide), GLP-1 active (glucagon-like peptide-1), glucagon, PYY (peptide YY), PP (pancreatic polypeptide), leptin, interleukin-6, MCP-1 (monocyte chemoattractant protein-1), and TNFα (tumor necrosis factor alpha) were measured, and correlations with ALSFRS-R, evolution scores, and biomarkers were analyzed using Spearman correlation coefficients. Subgroup analyses based on ALS subtypes, progression pattern of disease, and disease progression rate patterns were performed. Significant correlations were observed between metabolic hormones and ALS evolution scores. Insulin and amylin exhibited strong correlations with disease progression and clinical functional outcomes, with insulin showing particularly robust associations. Other hormones such as C-peptide, leptin, and GLP-1 also showed correlations with ALS progression and functional status. Subgroup analyses revealed differences in hormone levels based on sex and disease evolution patterns, with male patients showing higher amylin and glucagon levels. ALS patients with slower disease progression exhibited elevated levels of amylin and insulin. Our findings suggest a potential role for metabolic hormones in modulating ALS progression and functional outcomes. Further research is needed to elucidate the underlying mechanisms and explore the therapeutic implications of targeting metabolic pathways in ALS management.
Topics: Humans; Amyotrophic Lateral Sclerosis; Male; Female; Middle Aged; Aged; Islet Amyloid Polypeptide; Cross-Sectional Studies; Biomarkers; Insulin; Disease Progression; Leptin; Glucagon-Like Peptide 1; C-Peptide; Ghrelin; Glucagon; Adult; Hormones
PubMed: 38791099
DOI: 10.3390/ijms25105059 -
Nutricion Hospitalaria Dec 2023Background: infants receiving full breastfeeding (FBF) regulate their appetites differently from those receiving human milk substitutes (HMS). In addition, early...
Background: infants receiving full breastfeeding (FBF) regulate their appetites differently from those receiving human milk substitutes (HMS). In addition, early exposure to the dietary cholesterol in human milk could lead to better cholesterol regulation in later stages of life. Therefore, the purpose was to compare lipid profiles in 4-month-old infants and to correlate lipid profile with anthropometric indicators and appetite-regulating hormones according to the type of feeding. Methods: this was a cross-sectional and correlational study, which included 145 mother-infant dyads according to the type of feeding; 64 received FBF, 47 partial breastfeeding (PBF), and 34 HMS. The complete lipid profile, total ghrelin, leptin, peptide YY, and glucagon-like peptide type 1 were measured. Z-scores for weight/age, length/age, weight/length, triceps (TSF) and subscapular folds (SSF) and body mass index for age were also obtained. Results: there were significant differences in triglycerides and LDL cholesterol according to the type of feeding. In the HMS group, an inverse relationship was observed between ghrelin and triglycerides (p = 0.038), ghrelin and total cholesterol (TC) (p = 0.026), and peptide YY and HDL cholesterol (p = 0.017). In the PBF group, a direct relationship was observed between length/age (z) and triglycerides (p = 0.001) and between subscapular folds and TC (p = 0.049). In infants receiving HMS, a direct correlation was observed between weight/age (z) and TC (p = 0.045) and between length/age (z) and LDL cholesterol (p = 0.010). Conclusion: these findings show a relationship between growth, energy reserve, lipid profile, and modulation of appetite-regulating hormones according to the type of feeding they received.
Topics: Infant; Female; Humans; Ghrelin; Appetite; Cholesterol, LDL; Peptide YY; Cross-Sectional Studies; Breast Feeding; Cholesterol; Triglycerides
PubMed: 37522456
DOI: 10.20960/nh.04477 -
BMC Cardiovascular Disorders Dec 2023To analyze the association of serum Asprosin concentrations with heart failure (HF).
BACKGROUND
To analyze the association of serum Asprosin concentrations with heart failure (HF).
METHODS
A total of 103 patients with HF were included in the HF group, and 103 patients with health checkups were included in the non-HF group. The serum Asprosin levels of the two groups were measured, and relevant clinical data were collected for statistical analysis.
RESULTS
Compared with the non-HF group, the serum Asprosin concentration was significantly higher in the HF group, and the difference was statistically significant (P < 0.001). According to the serum Asprosin levels, we divided all the subjects into three quartiles. We found that the prevalence of HF increased with increasing serum Asprosin levels in the three groups (P < 0.001). Serum Asprosin levels were positively correlated with NT-ProBNP (P < 0.05) and negatively correlated with LVEF (P < 0.001). Dichotomous logistic regression analysis found Asprosin and age to be independent risk factors for HF (OR = 1.010, 95% CI: 1.003-1.018; OR = 1.058, 95% CI:1.004-1.665, respectively). Combining Asprosin and NT-proBNP indicators to draw ROC curves can improve the specificity and sensitivity of HF diagnosis.
CONCLUSIONS
Serum Asprosin levels were significantly elevated in HF patients. The serum Asprosin level is an independent risk factor for HF, and the combined detection of Asprosin and NT-proBNP levels can improve the accuracy of HF diagnosis.
Topics: Humans; Heart Failure; ROC Curve; Risk Factors; Natriuretic Peptide, Brain; Peptide Fragments; Biomarkers
PubMed: 38097977
DOI: 10.1186/s12872-023-03668-z -
Journal of Eating Disorders Jul 2023Avoidant/restrictive food intake disorder (ARFID) is a restrictive eating disorder commonly associated with medical complications of undernutrition and low weight. In...
BACKGROUND
Avoidant/restrictive food intake disorder (ARFID) is a restrictive eating disorder commonly associated with medical complications of undernutrition and low weight. In adolescence, a critical time for bone accrual, the impact of ARFID on bone health is uncertain. We aimed to study bone health in low-weight females with ARFID, as well as the association between peptide YY (PYY), an anorexigenic hormone with a role in regulation of bone metabolism, and bone mineral density (BMD) in these individuals. We hypothesized that BMD would be lower in low-weight females with ARFID than healthy controls (HC), and that PYY levels would be negatively associated with BMD.
METHODS
We performed a cross-sectional study in 14 adolescent low-weight females with ARFID and 20 HC 10-23 years old. We assessed BMD (total body, total body less head and lumbar spine) using dual x-ray absorptiometry (DXA) and assessed fasting total PYY concentration in blood.
RESULTS
Total body BMD Z-scores were significantly lower in ARFID than in HC (- 1.41 ± 0.28 vs. - 0.50 ± 0.25, p = 0.021). Mean PYY levels trended higher in ARFID vs. HC (98.18 ± 13.55 pg/ml vs. 71.40 ± 5.61 pg/ml, p = 0.055). In multivariate analysis within the ARFID group, PYY was negatively associated with lumbar BMD adjusted for age (β = -0.481, p = 0.032).
CONCLUSION
Our findings suggest that female adolescents with low-weight ARFID may have lower BMD than healthy controls and that higher PYY levels may be associated with lower BMD at some, but not all, sites in ARFID. Further research with larger samples will be important to investigate whether high PYY drives bone loss in ARFID.
PubMed: 37393263
DOI: 10.1186/s40337-023-00822-y -
Appetite May 2024Research on exercise-induced appetite suppression often does not include resistance training (RT) exercise and only compared matched volumes.
UNLABELLED
Research on exercise-induced appetite suppression often does not include resistance training (RT) exercise and only compared matched volumes.
PURPOSE
To compare the effects of low-load and high-load RT exercise completed to volitional fatigue on appetite-regulation.
METHODS
11 resistance-trained males (24 ± 2 y) completed 3 sessions in a crossover experimental design: 1) control (CTRL); 2) RT exercise at 30% 1-repetition maximum (RM); and 3) RT exercise at 90% 1-RM. RT sessions consisted of 3 sets of 5 exercises completed to volitional fatigue. Acylated ghrelin, active glucagon-like peptide-1 (GLP-1), active peptide tyrosine (PYY), lactate, and subjective appetite perceptions were measured pre-exercise, 0-, 60-, and 120-min post-exercise. Energy intake was recorded the day before, of, and after each session.
RESULTS
Lactate was elevated following both 30% (0-, 60-, 120-min post-exercise) and 90% (0-, 60-min post-exercise; P < 0.001, d > 3.92) versus CTRL, with 30% greater than 90% (0-min post-exercise; P = 0.011, d = 1.14). Acylated ghrelin was suppressed by 30% (P < 0.007, d > 1.22) and 90% (P < 0.028, d > 0.096) post-exercise versus CTRL, and 30% suppressed concentrations versus 90% (60-min post-exercise; P = 0.032, d = 0.95). There was no effect on PYY (P > 0.171, η <0.149) though GLP-1 was greater at 60-min post-exercise in 90% (P = 0.052, d = 0.86) versus CTRL. Overall appetite was suppressed 0-min post-exercise following 30% and 90% versus CTRL (P < 0.013, d > 1.10) with no other differences (P > 0.279, d < 0.56). There were no differences in energy intake (P > 0.101, η <0.319).
CONCLUSIONS
RT at low- and high-loads to volitional fatigue induced appetite suppression coinciding with changes in acylated ghrelin though limited effects on anorexigenic hormones or free-living energy intake were present.
Topics: Male; Humans; Appetite; Ghrelin; Resistance Training; Peptide YY; Appetite Regulation; Glucagon-Like Peptide 1; Energy Intake; Lactic Acid
PubMed: 38417533
DOI: 10.1016/j.appet.2024.107286 -
Frontiers in Pharmacology 2024Bone is a highly dynamic organ that changes with the daily circadian rhythm. During the day, bone resorption is suppressed due to eating, while it increases at night.... (Review)
Review
Bone is a highly dynamic organ that changes with the daily circadian rhythm. During the day, bone resorption is suppressed due to eating, while it increases at night. This circadian rhythm of the skeleton is regulated by gut hormones. Until now, gut hormones that have been found to affect skeletal homeostasis include glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), and peptide YY (PYY), which exerts its effects by binding to its cognate receptors (GLP-1R, GLP-2R, GIPR, and Y1R). Several studies have shown that GLP-1, GLP-2, and GIP all inhibit bone resorption, while GIP also promotes bone formation. Notably, PYY has a strong bone resorption-promoting effect. In addition, gut microbiota (GM) plays an important role in maintaining bone homeostasis. This review outlines the roles of GLP-1, GLP-2, GIP, and PYY in bone metabolism and discusses the roles of gut hormones and the GM in regulating bone homeostasis and their potential mechanisms.
PubMed: 38725663
DOI: 10.3389/fphar.2024.1372399 -
Frontiers in Endocrinology 2023To verify whether the oral insulin N11005 is administered as a prandial insulin by assessing the pharmacokinetics (PK), pharmacodynamics (PD), and safety profiles of... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
To verify whether the oral insulin N11005 is administered as a prandial insulin by assessing the pharmacokinetics (PK), pharmacodynamics (PD), and safety profiles of N11005 with a short-acting biosynthetic human insulin (Novolin R) as reference.
METHODS
This was a randomized, open-label, single-dose, crossover hyperinsulinemic-euglycemic clamp study in healthy Chinese male subjects. A total of 12 subjects were enrolled in the test (T) group (N11005, 300 IU, p.o.) and the reference (R) group (Novolin R, 0.1 IU/Kg, i.h.) with a washout period of 14 days. All subjects were administered on the same day of the clamp study. Glucose Infusion Rates (GIR), serum insulin, and C-peptide concentration were determined during every 8-hour clamp cycle. Trial registration: Clinicaltrials.gov identifier NCT04975022.
RESULTS
After administration, the ratios of mean serum C-peptide concentration to baseline concentration in both T and R groups were lower than 50%, which confirmed the stability of the clamp platform. T group (N11005) showed a more rapid onset of action (tGIR≈11 min) and a comparable duration of action to the R group, which was basically in line with the characteristics of prandial insulins. No adverse events (AEs) occurred throughout the study, which demonstrated that N11005 and Novolin R are safe and well-tolerated.
CONCLUSIONS
The PD profiles of the single-dose N11005 in the human body are similar to those of prandial insulins, with an excellent safety profile.
CLINICAL TRIAL REGISTRATION
Clinicaltrials.gov, identifier NCT04975022.
Topics: Humans; Male; C-Peptide; Glucose Clamp Technique; Healthy Volunteers; Insulin; Cross-Over Studies
PubMed: 37564986
DOI: 10.3389/fendo.2023.1172327 -
Diabetes Research and Clinical Practice Sep 2023To understand glucagon-like peptide-1 receptor agonist (GLP-1RA) use in patients with type 2 diabetes (T2D) in Japan.
AIMS
To understand glucagon-like peptide-1 receptor agonist (GLP-1RA) use in patients with type 2 diabetes (T2D) in Japan.
METHODS
Characteristics of people receiving GLP-1RAs between 2016 and 2020 in the J-DREAMS database were investigated. Changes in HbA, body weight (BW), body mass index (BMI), and proportion reaching HbA targets were analysed in GLP-1RA-naïve patients 6-24 months after GLP-1RA initiation.
RESULTS
The proportion of patients with GLP-1RA prescriptions increased from 3.6% to 9.6% during 2016-2020. Among GLP-1RA-naïve patients (n = 569), HbA reduced -0.6% (95% confidence interval [CI] -0.7, -0.5; -6 mmol/mol [95% CI -7, -5]) 6 months after treatment initiation and stabilised until 24 months (P < 0.001); mean BW and BMI reduced -1.05 kg (95% CI -1.31, -0.80) and -0.43 kg/m (95% CI -0.53, -0.32), respectively, at 6 months (P < 0.001). The proportion of GLP-1RA-naïve patients with HbA < 7.0% (<53 mmol/mol) and <8.0% (<64 mmol/mol) increased from 16% to 27% and 43% to 65%, respectively, and an HbA reduction of ≥1.0% (≥11 mmol/mol) was observed in 33% of patients after 6 months (P < 0.001).
CONCLUSIONS
This study shows increased GLP-1RA prescriptions over 5 years. HbA and BW reduced 6 months after GLP-1RA initiation in patients with T2D in a Japanese real-world setting.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glucagon-Like Peptide-1 Receptor; Retrospective Studies; East Asian People; Glycated Hemoglobin; Body Weight
PubMed: 37481115
DOI: 10.1016/j.diabres.2023.110841 -
Peptides Nov 2023Glucagon-like peptide 2 (GLP-2) is an important regulator of intestinal growth and function. In adherable mixed meals the macronutrient composition with the best... (Randomized Controlled Trial)
Randomized Controlled Trial
Glucagon-like peptide 2 (GLP-2) is an important regulator of intestinal growth and function. In adherable mixed meals the macronutrient composition with the best potential for stimulating GLP-2 secretion is not known. We compared the effect of 3 iso-energetic meals, where approximately 60 % of the energy ratio was provided as either carbohydrate, fat, or protein, respectively, on the post-prandial endogenous GLP-2 secretion. The responses were compared to secretion profiles of peptide YY (PYY), and glucose-dependent insulinotropic peptide (GIP). Ten healthy subjects were admitted on three occasions, at least a week apart, after a night of fasting. In an open-label, crossover design, they were randomized to receive a high carbohydrate (HC), high fat (HF) or high protein (HP) meal. The meals were approximately ∼3.9 MJ. Venous blood was collected for 240 min, and plasma concentrations of GLP-2, GIP and PYY were measured with specific radioimmunoassays. Mean GLP-2 levels peaked already at 30 min for the HC meal, however the HP meal induced the highest mean GLP-2 peaking levels, resulting in significantly higher mean GLP-2 area under the curve (AUC) from baseline of 7279 pmol*min/L, 95 %-CI [6081;8477] compared to the HC meal: 4764 pmol*min/L, 95 %-CI [3498;6029], p = 0.020 and the HF meal: 4796 pmol*min/L, [3385;6207], p = 0.011. Findings were similar for the PYY. The HC meal provided a greater AUC for GIP compared to the HP- and HF meals. The HP meal was most effective with respect to stimulation of the postprandial GLP-2 and PYY secretion, whereas the HC meal was more effective for GIP.
Topics: Humans; Carbohydrates; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 2; Healthy Volunteers; Meals; Nutrients; Peptide YY; Cross-Over Studies
PubMed: 37640265
DOI: 10.1016/j.peptides.2023.171091