The living record of
peptide science.

Acute interleukin-1β antagonism decreases systemic inflammation, increases GLP-1 release, and modulates insulin secretion in individuals with prediabetes.

Am J Physiol Endocrinol Metab

Justus S Fischer, Matthias Hepprich, Marco Cattaneo +3 more

Metabolic stress in obesity and diabetes activates innate immunity. Chronic IL-1β antagonism improves insulin secretion in type 2 diabetes. However, it is unclear how rapidly this effect occurs, whether it is also present in individuals with prediabetes, and if IL-1β influences GLP-1 secretion. Therefore, we acutely antagonized IL-1β in patients with prediabetes overnight. Two injections of anakinra significantly reduced total leucocyte count (P < 0.001), neutrophils (P < 0.001), monocytes (P = 0.006), and CRP (P = 0.030) compared with placebo. Lymphocytes were slightly elevated (P = 0.045). A mixed meal tolerance tests showed a trend toward increased early insulin (P = 0.11) and GLP-1 responses (P = 0.055), with GLP-1 (P = 0.020) and glucagon (P = 0.003) levels being significantly higher at 120 min under anakinra. Cytokine analysis showed elevated baseline concentrations of IL-1β, IL-6, and IL-1Ra under anakinra (all P < 0.001), with IL-1β (P < 0.001) and IL-18BP (P = 0.048) decreased, and IL-6 increased (P = 0.059) after 60 min. Therefore, an acute injection of anakinra significantly reduces CRP and leucocyte counts in individuals with prediabetes, indicating effective innate immune modulation even after immediate treatment. Despite seeing no significant improvements in insulin secretion or glucose metabolism, we observed a trend toward earlier insulin secretion, along with increased release of IL-6 and GLP-1. We conclude that acute IL-1 antagonism dampens systemic inflammation in prediabetes, with the potential to improve insulin secretion via IL-6-induced GLP-1.NEW & NOTEWORTHY Acute IL-1 blockade with anakinra markedly reduced CRP and leukocyte counts within 12 h, demonstrating rapid anti-inflammatory efficacy. Anakinra induced a trend toward earlier insulin secretion and significantly increased postprandial IL-6 and GLP-1 levels. The study demonstrates that even short-term IL-1 blockade can modulate both immune and incretin responses in prediabetes. Early IL-1β antagonism may represent a preventive, anti-inflammatory approach to preserve GLP-1 secretion and β-cell function in individuals with prediabetes.

Brainstem GLP-1 neurons modulate physiological satiation and drive sustained weight loss in obese mice.

Mol Metab

Wanqing Jiang, Cecilia Skoug, Ian Rodrigues +6 more

Glucagon-like peptide-1 receptor (GLP-1R) activation in the brain strongly reduces appetite, but most brain GLP-1Rs are not accessible for systemically administered GLP-1R agonists. Acute activation of nucleus tractus solitarius (NTS) GLP-1 neurons, known as preproglucagon (PPG) neurons, strongly suppresses food intake separate from GLP-1R agonists. However, it is unknown if chronic stimulation of PPG neurons is a viable strategy for appetite suppression, or if obesity disrupts their function. Here we demonstrate that PPG neurons in the NTS and intermediate reticular nucleus (IRT) determine meal size, and that their total number is inversely correlated with bodyweight gain. We report that PPGNTS and PPGIRT neurons receive distinct monosynaptic inputs, but have convergent efferent projection targets throughout the brain, and that combined ablation of both populations delays the onset of physiological satiation to a degree sufficient to promote weight gain under ad libitum chow fed conditions. Crucially, chronic daily chemogenetic activation of PPGNTS+IRT neurons drives robust and sustained hypophagia and weight loss in obese mice without notable adverse effects, demonstrating their value as targets for obesity pharmacotherapy.

Glucagon-like peptide-1 agonists' effects on glycemic control, weight loss, and beta cells function in type 1 diabetes.

Front Endocrinol (Lausanne)

Hyder O Mirghani, Laila Albishi, Sawsan Mohmed Alblewi

Insulin is an effective treatment for type 1 diabetes mellitus (T1DM), and a significant proportion of patients are not controlled, develop hypoglycemia, and gain weight. Therefore, adjuvant therapies to mitigate the above are highly needed. Meta-analyses on the effect of glucagon peptide agonists (GLP-1 agonists) on weight loss and HbA1c are scarce. We aimed to assess the effects of GLP-1 agonists on HbA1c, weight, and C-peptide in patients with T1DM with obesity/overweight and normal weight.

Semaglutide Plus Low-Dose Metformin Combination Therapy for the Treatment of Obesity and Prediabetes in a Woman with Partial Deletion of the X Chromosome Long Arm.

Reports (MDPI)

Vincenzo Marzolla, Stefania Gorini, Massimiliano Caprio +1 more

Background and Clinical Significance: Over the last two decades, glucagon-like peptide-1 (GLP-1) receptor agonists have dramatically improved the management of type 2 diabetes mellitus and obesity. Currently, little is known about the use of semaglutide (a second-generation GLP-1 receptor agonist) in patients with X chromosome abnormalities. Herein, we describe the therapeutic use of semaglutide in a woman with a partial deletion of the X chromosome long arm (partial Xq deletion) and comorbid obesity. We also conducted a narrative mini-review on overweight, obesity and common metabolic derangements in patients with partial Xq deletions and Turner syndrome. Case Presentation: A 65-year-old Italian woman with a partial Xq deletion, class 1 obesity, insulin resistance, prediabetes, hypercholesterolemia and metabolic dysfunction-associated steatotic liver disease (MASLD) was referred to our Institution for persistent difficulty in managing excess body weight despite regular adherence to different structured physical activity programs and hypocaloric diets. Therefore, we prescribed a combination therapy based on low-dose metformin (500 mg/day) and once-weekly subcutaneous semaglutide (as an adjunct to lifestyle intervention). At 5 months after initiation of the combination therapy, blood tests showed metabolic improvements, including improvement of prediabetes (0.3-percentage-point reduction in glycated hemoglobin [HbA1c] values) and normalization of markers of insulin sensitivity and insulin resistance (QUICKI, HOMA-IR and TyG index). At 8 months, the patient showed substantial weight loss, which amounted to 13.8 kg (percent total body weight loss: 20.95%), and was accompanied by a notable reduction in waist circumference (-14.1 cm). Moreover, body mass index (BMI)-based weight status improved from class 1 obesity to overweight: BMI value of 25.1 kg/m2 at 8 months vs. 31.8 kg/m2 at baseline (near-normalization of BMI values). Bioelectrical impedance analysis (BIA) revealed that the patient's overall weight loss consisted of 74.6% fat mass (FM) loss (-10.3 kg) and 25.4% fat-free mass (FFM) loss (-3.5 kg). Despite the expected FFM reduction in absolute terms, percent FFM increased at 8 months (+9.6%). This increase in percent FFM was accompanied by a reduction in percent FM at 8 months (-9.6%), indicating an overall improvement in body composition. Normalization of percent FM and FFM values (28.6% and 71.4%, respectively) was also achieved at 8 months. These body composition changes are in line with those observed in clinical trials investigating the use of semaglutide in patients with overweight or obesity. At 6 months, an abdominal ultrasound also showed the disappearance of the sonographic characteristics suggestive of mild-to-moderate hepatic steatosis. Low-dose metformin (500 mg/day) and subcutaneous semaglutide (up to a weekly dose of 1.7 mg) were well tolerated by the patient. Conclusions: To the best of our knowledge, this is the first case documenting the effective use of once-weekly subcutaneous semaglutide plus low-dose metformin combination therapy for the treatment of obesity and prediabetes in a woman with a partial Xq deletion. Large prospective cohort studies are warranted to better investigate the safety and efficacy profile of semaglutide (alone or in combination with metformin) in patients with numerical and structural X chromosome abnormalities, comorbid overweight/obesity and related metabolic disorders.

Transient adrenocorticotropic hormone elevation with a disproportionate cortisol response prior to the onset of immune checkpoint inhibitor-related hypophysitis.

Hormones (Athens)

Hina Inui-Yasuda, Hironori Bando, Miki Watanabe +10 more

Hypothalamic-pituitary-adrenal axis activity and neurotrophic factors in drug-naive children and adolescents with attention-deficit/hyperactivity disorder.

Front Psychiatry

Hurşit Ferahkaya, Necati Uzun, Hasibe Ağır +5 more

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a complex and not fully understood etiology. Increasing evidence suggests that neurotrophic factors involved in neurodevelopment and synaptic plasticity, as well as hormones of the hypothalamic-pituitary-adrenal (HPA) axis that regulate the stress response, may contribute to the pathophysiology of ADHD.

Pulmonary neuroendocrine tumour-associated ectopic Cushing's syndrome: diagnostic challenges and multidisciplinary management.

Endocrinol Diabetes Metab Case Rep

Rubén D Carrasco B, Alba Juanes, Carmen Marrón +3 more

Ectopic adrenocorticotropic hormone (ACTH) secretion is a rare cause of Cushing's syndrome (CS), often associated with neuroendocrine tumours (NETs). Early diagnosis can be difficult due to variable clinical manifestations and psychiatric symptoms that may obscure the underlying endocrine disorder. We report a case of severe ectopic ACTH-dependent Cushing's syndrome secondary to a pulmonary NET, highlighting the importance of multidisciplinary management, advanced imaging with positron emission tomography/computed tomography with gallium-68-labelled DOTA-D-Phe-Tyr-octreotide (68Ga-DOTATOC PET-CT) and aggressive biochemical control to enable curative surgery and full clinical recovery.

Titanium nanotube arrays promote the activity of anastomotic healing-related cells by increasing fibronectin adsorption and activating the RGD-integrin pathway.

Biomed Mater

Pengyu Chen, Bang Liu, Yijia Li +2 more

The smooth titanium staples of stapling devices cannot reduce the incidence of gastrointestinal anastomotic leakage due to their bioinert nature and lack of active wound-healing promotion capability. This study aims to investigate whether titanium nanotube arrays (TNTs) can enhance the activity of cells involved in gastrointestinal anastomotic healing and further explore the potential mechanisms. TNTs were fabricated on pure titanium sheets via anodic oxidation, and characterized using scanning electron microscopy, roughness analysis, contact angle measurement, and x-ray photoelectron spectroscopy. Cell adhesion, proliferation, spreading, collagen secretion, and integrin expression were evaluated using methods such as CCK-8, immunofluorescence, qPCR, enzyme-linked immunosorbent assay (ELISA), and Western blot. Fibronectin (FN) adsorption and Arg-Gly-Asp tripeptide sequence (RGD domain) exposure were detected via bicinchoninic acid assay, fluorescent staining, and ELISA. The role of the RGD-integrin pathway was further investigated by supplementing serum-reduced medium with exogenous FN and using RGD-specific antagonists. The results showed that TNTs increased the roughness, hydrophilicity, and surface free energy of titanium surfaces. Compared with smooth pure titanium, TNTs promoted the adhesion, proliferation, spreading, and integrin expression of gastric mucosal epithelial cells and fibroblasts, while enhancing the collagen secretion capacity of fibroblasts. Moreover, TNTs adsorbed more FN and exposed more RGD domains, thereby upregulating integrinα5β1 expression. The RGD antagonist could reverse these enhanced cellular responses, confirming the pivotal role of the FN-RGD-integrin pathway. The conclusion indicates that TNTs enhance the adhesion, proliferation, and functional activity of gastrointestinal anastomosis-related cells by promoting FN adsorption and activating the RGD-integrin pathway, which demonstrates that TNT-modified titanium materials hold significant potential for developing bioactive anastomotic devices and promoting tissue healing.

Earthworm Powder Mitigates Soybean Meal-Induced Growth Inhibition in Rice Field Eel (Monopterus albus) by Regulating Appetite and Improving Intestinal Health.

Biology (Basel)

Kaiwen Hou, Hui Wang, Lin Zhang +7 more

The substitution of fish meal with soybean meal (SBM) in aquafeeds aligns with sustainable development but often leads to depressed feed intake and growth in fish. This study aimed to investigate the mitigating effect of earthworm powder (EP) on these negative impacts in rice field eels (Monopterus albus), focusing on appetite regulation, intestinal health, and gut microbiota. Three isonitrogenous (~41% crude protein) and isolipidic (~6.4% crude lipid) diets (control [CON], high-SBM [SBM], and SBM + 2.5% EP [EP]) were tested in a 56-day trial. Juveniles (initial weight 18.00 ± 0.01 g) were stocked at 40 fish per net (0.5 m × 0.5 m× 0.5 m) and fed to visual satiety once daily. The results indicated that EP improved growth performance through a dual mechanism. Firstly, it was associated with significantly increased feed intake, correlated with the upregulated expression of orexigenic genes (agrp, npy) in the brain, and associated with reduced levels of anorexigenic hormones (Cholecystokinin, Leptin). Secondly, it correlated with enhanced intestinal health, evidenced by improved morphology (villus height, goblet cells), improved digestive enzyme activity, enhanced antioxidant capacity (increased Catalase and Superoxide Dismutase activities), repaired intestinal barrier function (upregulated zo-1, cla-12), and alleviated intestinal inflammation (downregulated tnf-α, il-1β). Furthermore, EP supplementation was associated with a shift in gut microbiota, including the suppression of the potential pathogen g_Clostridium_T and promotion of the beneficial bacterium g_Lactococcus_A, alongside increased concentrations of major short-chain fatty acids (acetate, propionate, and butyrate). These correlative observations suggest that EP may help mitigate the growth-inhibiting effects of SBM in Monopterus albus, offering a potential functional strategy for high-SBM aquafeeds.

Involvement of peripheral and central sensitization in prolonged mechanical allodynia of the tongue in a rat.

Odontology

Saki Kishimoto, Sho Katsura, Yoshie Okamoto +3 more

This study aimed to characterize peripheral and central sensitization in mechanical allodynia of the tongue induced by sleep-related disorders, neuropathic pain, and inflammatory pain. Male rats were exposed to chronic intermittent hypoxia (CIH) for 16 days using an obstructive sleep apnea model. Lingual nerve injury (LNI) was induced to establish a neuropathic tongue pain model, while complete Freund's adjuvant was injected into the tongue to establish a tongue inflammation (TI) model. The expression levels of calcitonin gene-related peptide (CGRP), hypoxia-inducible factor (HIF)-1α, piezo-type mechanosensitive ion channel component 2 (Piezo2), transient receptor potential cation channel subfamily V member 4 (TRPV4), and glial fibrillary acidic protein (GFAP) in the trigeminal ganglion (TG) and cFos in the trigeminal spinal subnucleus were determined using immunohistochemistry on day 16. All CIH, LNI, and TI rat models exhibited prolonged mechanical allodynia of the tongue. CIH and TI increased the number of CGRP-immunoreactive (IR) neurons and HIF-1α-IR cells. However, only CIH increased the number of Piezo2-IR neurons and GFAP-positive satellite glial cells. The number of TRPV4-IR neurons was elevated in the LNI and TI groups but not in the CIH group. Only CIH induced persistent cFos expression in the trigeminal spinal subnucleus caudalis, indicating long-lasting central sensitization. These findings indicate that CIH-induced tongue pain arises through distinct peripheral and central sensitization processes, highlighting the diverse mechanisms underlying chronic mechanical allodynia of the tongue.

The expression characteristics of miR-206-3p in musculoskeletal tissue and its clinical significance.

J Orthop Surg Res

Khan Akhtar Ali, Xuefeng Yuan, Tianxiang Cui +3 more

Osteosarcopenia, a comorbidity of osteoporosis and sarcopenia in the elderly, involves bone-muscle crosstalk, but its core molecular mechanism remains unclear. miR-206 is traditionally considered muscle-specific; this study explores miR-206-3p's expression in musculoskeletal tissue and correlation with clinical parameters.

Cellular Senescence in Skeletal Muscle: Myogenic and Non-Myogenic Cell Populations, Mechanisms, and Therapeutic Opportunities.

Am J Physiol Cell Physiol

Konstantinos Papanikolaou, Angad Yadav, Robert T Mankowski +5 more

Skeletal muscle plays a central role in systemic metabolism, physical function, and overall health. Aging and disease diminish the ability of myogenic and non-myogenic skeletal muscle cells to coordinate adaptation and repair, but the mechanisms underlying this decline are not fully understood. Growing evidence implicates cellular senescence, a stress response marked by irreversible cell-cycle arrest and pro-inflammatory signaling, as a key contributor to muscle pathology. In this review, we synthesize current insights into the molecular mechanisms that govern cellular senescence in skeletal muscle, its effects on myogenic and non-myogenic cell populations, and recent technologies that have clarified key aspects of senescence biology. We further explore emerging therapeutic strategies aimed at targeting senescent cells and discuss key knowledge gaps that must be addressed to advance our understanding of senescent myogenic and non-myogenic cells in skeletal muscle.

Tirzepatide as adjunct therapy in patients with type 1 diabetes: a systematic review and meta-analysis.

J Diabetes Metab Disord

Ahmed Soliman, Bishoy Hamour, Abdelwahab Hammad +7 more

Tirzepatide, a dual agonist of the glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1R) receptors, has demonstrated efficacy in glycemic control and weight loss in patients with Type 2 diabetes mellitus (T2DM). Its role as adjunctive therapy in individuals with Type 1 diabetes mellitus (T1DM), particularly those who are overweight or obese, remains underexplored. This review aims to evaluate the efficacy of tirzepatide as an adjunct to insulin therapy in adults with Type 1 diabetes mellitus (T1DM) and overweight or obesity, focusing on changes in glycemic control, body weight, body mass index (BMI), and insulin dose requirements.

Incretin polyagonists as an alternative to bariatric surgery to manage obesity.

World J Gastrointest Pathophysiol

Rohit Jacob Manoj, Cornelius J Fernandez, Sunil Nair +1 more

Incretins are gut hormones involved in maintaining metabolic homeostasis in the human body, and disorders of the incretin system are recognized as contributing to the pathobiology of metabolic dysfunction and obesity. Incretin polyagonists are transforming the landscape of obesity treatment by offering potent, non-surgical alternatives to bariatric procedures. Acting on multiple incretin and related receptors, these novel pharmacological agents harness the synergistic effects of gut hormones such as glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, and glucagon to achieve unprecedented weight loss and metabolic improvements. Recent clinical trials demonstrate that dual and triple agonists can produce weight reductions comparable to, or in some cases approaching, those seen with bariatric surgery, while simultaneously improving glycemic control, lipid profiles, liver fat, and cardiovascular risk factors. Unlike conventional monotherapies, these polyagonists address the complexity of energy homeostasis and metabolic dysfunction in obesity, with some agents displaying a favorable side effect profile and thereby enhancing patient tolerability. Practical considerations, such as ease of administration, cost, long-term safety, and accessibility, remain evolving challenges; yet, incretin polyagonists have rapidly gained prominence in clinical guidelines for the management of obesity and type 2 diabetes mellitus. As evidence mounts regarding their efficacy, safety, and potential to modify cardiometabolic disease risk, incretin polyagonists emerge as promising alternatives, especially for patients unable or unwilling to undergo bariatric surgery. Ongoing research will further define their long-term role, comparative effectiveness, and optimal integration into multidisciplinary obesity care. This review discusses the current evidence-base for optimal use of incretin polyagonists as an alternative to bariatric surgery.

Glucagon-like Peptide-1 Receptor Agonists in Liver Transplant Recipients: A Retrospective Cohort Study.

Transplant Direct

Hesham Sheashaa, Ramzi Ibrahim, Amani Elshaer +14 more

Liver transplant recipients face high risks of cardiometabolic events after transplant, driven by posttransplant weight gain, diabetes, hypertension, as well as immunosuppression-related side effects. Glucagon-like peptide-1 receptor agonists (GLP1RAs) improve metabolic and cardiorenal outcomes in nontransplant populations, but their role in liver transplant recipients remains understudied.

Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials.

JAMA Netw Open

Rodolfo J Galindo, Kimberly A Gudzune, Michelle Look +5 more

Given the common use of weight-inducing (WI) medications, it is crucial to understand the potential association of these medications with the effectiveness of obesity treatments.

Not All GLP-1 Receptor Agonists Are Alike: Real-World Evidence of Differential Endocrine and Dermatologic Safety.

Diabetes Metab Res Rev

Nai Lee, Yun Kim

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for metabolic disorders, but emerging safety concerns include alopecia and reproductive or endocrine-related adverse events (AEs). This study investigated the association between specific GLP-1 RAs and these endocrine-related AEs using a large-scale pharmacovigilance database.

New and currently investigated pharmacotherapies for the erythropoietic protoporphyrias: spotlight on dersimelagon and bitopertin.

Expert Opin Pharmacother

Jasmin Barman-Aksözen, Francesca Granata, Sebastian Wäscher +2 more

The erythropoietic protoporphyrias (EPP) are ultra-rare inborn errors of the heme biosynthesis characterized by painful and debilitating phototoxic reactions in the blood vessels upon exposure to visible light. Afamelanotide is the only approved treatment for EPP and effectively prevents pain and prolongs the time patients can spend in sunlight. However, afamelanotide does not address the underlying disease mechanism and is currently only approved for use in adult patients, leaving children and adolescents without a treatment option. The two investigational pharmacotherapies dersimelagon and bitopertin could offer benefits such as treatment options for children and prevention of some of the associated disease complications.

Angiotensin-(1-7) Alleviates Isoproterenol-Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor.

Acta Physiol (Oxf)

Xiaomei Wang, Fei Guo, Xiaoqian Wang +4 more

The aim of this study is to determine whether Angiotensin-(1-7) [Ang-(1-7)] alleviates isoproterenol (ISO)-induced cardiac hypertrophy by suppressing excessive autophagy and apoptosis through coordinated Mas receptor (MasR) and angiotensin II type-2 receptor (AT2R) signaling, and to elucidate the underlying mechanisms.

Mid-regional pro-atrial natriuretic peptide in managing cardiovascular and cerebrovascular diseases.

Crit Rev Clin Lab Sci

Xu-Lei Hao, Gjin Ndrepepa, Wen-Qi Zheng +1 more

Mid-regional pro-atrial natriuretic peptide (MR-proANP), along with B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), is a type of natriuretic peptide hormone that is released by atrial muscle cells upon stress. Previous studies have shown that MR-proANP has high diagnostic accuracy for heart failure (HF) in several clinical settings, and it also helps in the risk stratification of patients with HF. In the general population, elevated MR-proANP levels indicate a high risk of cerebrovascular and cardiovascular diseases, including stroke and atrial fibrillation. In patients with established cardiovascular and cerebrovascular diseases, elevated MR-proANP levels are associated with a poor prognosis. This review summarizes the value and the use of MR-proANP in assessing the risk, diagnosis, and prognosis of patients with cardiovascular and cerebrovascular disease(s).