نتائج البحث

1

Comparative clinical outcomes of insulin degludec and insulin glargine 300 U/mL after switching from other basal insulins in real‐world patients with type 1 and type 2 diabetes

المؤلفون: Yukiko Hasegawa, Tetsuya Babazono, Junko Oya, Aki Katamine, Tomoko Nakagami, Yuichiro Kondo

المصدر: Journal of Diabetes Investigation, Vol 12, Iss 11, Pp 1983-1991 (2021)
Journal of Diabetes Investigation

مصطلحات موضوعية: Insulin degludec, Male, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Insulins, Insulin Glargine, Type 2 diabetes, 030204 cardiovascular system & hematology, Body Mass Index, chemistry.chemical_compound, 0302 clinical medicine, Japan, Drug Substitution, Insulin glargine 300 U/mL, General Medicine, Articles, Middle Aged, Insulin, Long-Acting, Treatment Outcome, Clinical Science and Care, Female, Original Article, medicine.drug, Adult, medicine.medical_specialty, 030209 endocrinology & metabolism, Real‐world clinical setting, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Aged, Retrospective Studies, Glycated Hemoglobin, Type 1 diabetes, Insulin glargine, business.industry, Insulin, medicine.disease, RC648-665, Endocrinology, Diabetes Mellitus, Type 1, Logistic Models, Basal (medicine), chemistry, Diabetes Mellitus, Type 2, Glycated hemoglobin, business

الوصف: Aims/Introduction To evaluate and compare the efficacy of insulin degludec (IDeg) and insulin glargine 300 U/mL (Gla300) 6 months after switching from other basal insulins by assessing the changes in glycated hemoglobin (HbA1c), body mass index (BMI), and insulin doses in patients with type 1 and type 2 diabetes in a real‐world clinical setting. Materials and Methods A total of 307 patients with type 1 diabetes and 294 patients with type 2 diabetes with HbA1c >7.0% were studied. Adjusted mean changes in HbA1c, BMI, and insulin doses were compared between IDeg (IDeg group) and Gla300 (Gla300 group) switchers. Multivariable logistic regression analyses were carried out to examine whether the IDeg or Gla300 group was associated with HbA1c or insulin dose reduction and BMI gain. Results HbA1c was significantly decreased in both the IDeg and Gla300 groups. Adjusted mean changes in HbA1c (approximately −0.3% and −0.5% in type 1 diabetes and type 2 diabetes patients, respectively) and BMI were similar between both groups. The mean change in insulin dose was slightly larger for dose reduction in the IDeg group than in the Gla300 group. Multivariable logistic regression models showed that the IDeg group was significantly associated with insulin dose reduction after adjusting for basal insulin type, insulin dose, and number of basal insulin injections at baseline and other confounding factors. Conclusions The current study suggested that IDeg and Gla300 have similar effects in reducing HbA1c and gaining BMI after switching from other basal insulins in Japanese patients with type 1 diabetes and type 2 diabetes. IDeg selection was associated with insulin dose reduction.
Insulin degludec and insulin glargine 300 U/mL showed similar values of reduction in glycated hemoglobin with body mass index almost unchanged 6 months after switching from other basal insulins in both type 1 and type 2 diabetes patients. Switching to insulin degludec was significantly associated with a reduction of basal and total insulin doses in both type 1 and type 2 diabetes patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cd8e343952d329f98d4b6977a3a8fce5Test
https://doaj.org/article/33e2f17798204034beea375b21f2d506Test

2

Serum urate and cardiovascular events in the DCCT/EDIC study

المؤلفون: Amisha Wallia, Samuel Dagogo-Jack, Ionut Bebu, Trevor J. Orchard, Barbara H. Braffett, Timothy J. Lyons, Alicia J. Jenkins, Arpita Basu, W. Timothy Garvey, Maria F. Lopes-Virella, John M. Lachin

المصدر: Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
Scientific Reports

الوصف: In type 2 diabetes, hyperuricemia is associated with cardiovascular disease (CVD) and the metabolic syndrome (MetS), but associations in type 1 diabetes (T1D) have not been well-defined. This study examined the relationships between serum urate (SU) concentrations, clinical and biochemical factors, and subsequent cardiovascular events in a well-characterized cohort of adults with T1D. In 973 participants with T1D in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), associations were defined between SU, measured once in blood collected 1997–2000, and (a) concurrent MetS and (b) incident ‘any CVD’ and major adverse cardiovascular events (MACE) through 2013. SU was higher in men than women [mean (SD): 4.47 (0.99) vs. 3.39 (0.97) mg/dl, respectively, p Trial registration clinicaltrials.gov NCT00360815 and NCT00360893.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0db6a0485c835ecd5ee1065359316a30Test
https://doaj.org/article/f9fee4388877495b97606fb3d560869cTest

3

Initial Basal and Bolus Rates and Basal Rate Variability During Pump Treatment in Children and Adolescents

المؤلفون: Samim Özen, Yasemin Atik Altınok, Şükran Darcan, Damla Gökşen, Günay Demir

المصدر: Journal of Clinical Research in Pediatric Endocrinology
JCRPE, Vol 13, Iss 2, Pp 198-203 (2021)

مصطلحات موضوعية: Male, Time Factors, Endocrinology, Diabetes and Metabolism, Physiology, Dawn phenomenon, Pediatrics, 0302 clinical medicine, Endocrinology, Bolus (medicine), American-Diabetes-Association, Insulin, 030212 general & internal medicine, insulin infusion pump therapy, Child, Morning, basal rates, Infusion Pumps, Implantable, Growth hormone secretion, Circadian Rhythm, Subcutaneous Insulin Infusion, Type 1 diabetes, Child, Preschool, Original Article, Female, Insulin pump, Adult, Basal rate, Adolescent, 030209 endocrinology & metabolism, RJ1-570, Diseases of the endocrine glands. Clinical endocrinology, European-Association, 03 medical and health sciences, Young Adult, Age, Insulin Infusion Systems, medicine, Humans, Hypoglycemic Agents, Circadian rhythm, basal insulin, business.industry, Mellitus, Consensus Statement, Infant, RC648-665, medicine.disease, Diabetes Mellitus, Type 1, Pediatrics, Perinatology and Child Health, Therapy, Insulin Resistance, Young-Adults, business, Appraisal

الوصف: Objective: Pump-treated children with type 1 diabetes (T1DM) have widely differing basal insulin (BI) infusion profiles for specific periods of the day. The pattern of BI requirements depends on the timing and magnitude of cortisol and growth hormone secretion within each age group. In adolescents and young adults, a decreased insulin sensitivity is seen, particularly in the early morning (dawn phenomenon) and to a lesser extent, in the late afternoon (dusk phenomenon). Different approaches exist for the inititation of basal rates. However, there is a lack of evidence-based recommendation, especially in young children. Usually the basal rates are set equally throughout day and night or the day is divided into tertiles. The aim of this study was to analyze the change of the initial, equally distributed, BI rates over the first year of standard insulin pump therapy. Methods: A total of 154 patients with T1DM, aged between 0 and 18 years, (n=5). Distribution of hourly basal rates at the initiation of the pump and at the end of first year were evaluated. Results: Median (range) age and diabetes duration was 14.46 (1.91-26.15) and 7.89 (1.16-17.15) years, respectively. Forty-four percent were male, 56% were female. Mean total insulin dose/kg in the whole cohort at the initiation and after one year of pump therapy was 0.86 +/- 0.23 U/kg and 0.78 +/- 0.19 U/kg, respectively and differed significantly between each age group (p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::042811ee54a19ba17a3880a5ce10811bTest
http://europepmc.org/articles/PMC8186333Test

4

Insulin micro-secretion in Type 1 diabetes and related microRNA profiles

المؤلفون: Anthony C Keech, Yoon Hi Cho, Ryan J. Farr, Emma S. Scott, David N O'Neal, Anandwardhan A. Hardikar, Paul Z. Benitez-Aguirre, Mugdha V. Joglekar, Andrzej S. Januszewski, Luke M. Carroll, Alicia J. Jenkins, Maria E. Craig, Yik Wen Loh, Wilson K. M. Wong, Kim C. Donaghue

المصدر: Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
Scientific Reports

مصطلحات موضوعية: Blood Glucose, Male, 0301 basic medicine, Diabetes duration, medicine.medical_treatment, Autoimmunity, 0302 clinical medicine, Insulin-Secreting Cells, Insulin Secretion, Medicine, Child, Aged, 80 and over, Multidisciplinary, C-Peptide, Age Factors, Middle Aged, Type 1 diabetes, Female, Adult, medicine.medical_specialty, Adolescent, Science, 030209 endocrinology & metabolism, Article, Young Adult, 03 medical and health sciences, Diabetes mellitus, Internal medicine, microRNA, Humans, Secretion, Circulating MicroRNA, Insulin secretion, Aged, Autoantibodies, Glycated Hemoglobin, business.industry, Insulin, medicine.disease, MicroRNAs, Diabetes Mellitus, Type 1, 030104 developmental biology, Endocrinology, Gene Expression Regulation, Genetic markers, Age of onset, business, Biomarkers

الوصف: The aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood ( 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n = 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p p p = 0.02, respectively]. In the childhood-onset group more people with longer diabetes duration (> 20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cbd5b712c5082c4c879f559920494d80Test
https://doaj.org/article/b1ec56fdb12a4c0cb5cb32be78d2f006Test

5

Parathyroid hormone receptor stimulation induces human adipocyte lipolysis and browning

المؤلفون: Niels Jessen, Bjørn Richelsen, Steen B. Pedersen, Peter Breining, Jacob B. Hansen, Mads Kjolby

المصدر: Breining, P, Pedersen, S B, Kjolby, M, Hansen, J B, Jessen, N & Richelsen, B 2021, ' Parathyroid hormone receptor stimulation induces human adipocyte lipolysis and browning ', European Journal of Endocrinology, vol. 184, no. 5, pp. 687-697 . https://doi.org/10.1530/EJE-20-0713Test

مصطلحات موضوعية: Adult, Male, endocrine system, medicine.medical_specialty, Adipose Tissue, Brown/metabolism, Lipolysis, Endocrinology, Diabetes and Metabolism, Receptor expression, Parathyroid hormone, Adipose tissue, Parathyroid Hormone/pharmacology, 030209 endocrinology & metabolism, White adipose tissue, Lipolysis/drug effects, Adipose Tissue/drug effects, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Adipose Tissue, Brown, Receptor, Parathyroid Hormone, Type 1/metabolism, Adipocyte, Internal medicine, Brown adipose tissue, Adipocytes, medicine, Humans, Uncoupling Protein 1, Receptor, Parathyroid Hormone, Type 1, Aged, Chemistry, Thermogenesis/drug effects, Thermogenesis, Uncoupling Protein 1/metabolism, General Medicine, Middle Aged, Thermogenin, Cross-Sectional Studies, medicine.anatomical_structure, Adipose Tissue, Parathyroid Hormone, 030220 oncology & carcinogenesis, Female, hormones, hormone substitutes, and hormone antagonists, Adipocytes/drug effects

الوصف: Objective Activation of brown adipose tissue is a promising strategy to treat and prevent obesity and obesity-related disorders. Activation of uncoupling protein 1 (UCP1) leads to uncoupled respiration and dissipation of stored energy as heat. Induction of UCP1-rich adipocytes in white adipose tissue, a process known as ‘browning’, serves as an alternative strategy to increase whole body uncoupling capacity. Here, we aim to assess the association between parathyroid hormone (PTH) receptor expression and UCP1 expression in human adipose tissues and to study PTH effects on human white and brown adipocyte lipolysis and UCP1 expression. Design A descriptive study of human neck adipose tissue biopsies substantiated by an interventional study on human neck-derived adipose tissue cell models. Methods Thermogenic markers and PTH receptor gene expression are assessed in human neck adipose tissue biopsies and are related to individual health records. PTH-initiated lipolysis and thermogenic gene induction are assessed in cultured human white and brown adipocyte cell models. PTH receptor involvement is investigated by PTH receptor silencing. Results PTH receptor gene expression correlates with UCP1 gene expression in the deep-neck adipose tissue in humans. In cell models, PTH receptor stimulation increases lipolysis and stimulates gene transcription of multiple thermogenic markers. Silencing of the PTH receptor attenuates the effects of PTH indicating a direct PTH effect via this receptor. Conclusion PTH 1 receptor stimulation by PTH may play a role in human adipose tissue metabolism by affecting lipolysis and thermogenic capacity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b9393d6212f2abdcb21a7db48ea58f29Test
https://doi.org/10.1530/eje-20-0713Test

6

RPS6 phosphorylation occurs to a greater extent in the periphery of human skeletal muscle fibers, near focal adhesions, after anabolic stimuli

المؤلفون: Nathan Hodson, Dinesh Kumbhare, Daniel R. Moore, Maksym N. H. Holowaty, Michael Mazzulla

المصدر: American Journal of Physiology-Cell Physiology. 322:C94-C110

الوصف: Following anabolic stimuli (mechanical loading and/or amino acid provision), the mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of protein synthesis, translocates toward the cell periphery. However, it is unknown if mTORC1-mediated phosphorylation events occur in these peripheral regions or before translocation (i.e., in central regions). We therefore aimed to determine the cellular location of a mTORC1-mediated phosphorylation event, RPS6Ser240/244, in human skeletal muscle following anabolic stimuli. Fourteen young, healthy males either ingested a protein-carbohydrate beverage (0.25 g/kg protein and 0.75 g/kg carbohydrate) alone [ n = 7; 23 ± 5 yr; 76.8 ± 3.6 kg; and 13.6 ± 3.8% body fat (BF), FED] or following a whole body resistance exercise bout ( n = 7; 22 ± 2 yr; 78.1 ± 3.6 kg; and 12.2 ± 4.9%BF, EXFED). Vastus lateralis muscle biopsies were obtained at rest (PRE) and 120 and 300 min following anabolic stimuli. RPS6Ser240/244 phosphorylation measured by immunofluorescent staining or immunoblot was positively correlated ( r = 0.76, P < 0.001). Peripheral staining intensity of p-RPS6Ser240/244 increased above PRE in both FED and EXFED at 120 min (∼54% and ∼138%, respectively, P < 0.05) but was greater in EXFED at both poststimuli time points ( P < 0.05). The peripheral-to-central ratio of p-RPS6240/244 staining displayed a similar pattern, even when corrected for total RPS6 distribution, suggesting RPS6 phosphorylation occurs to a greater extent in the periphery of fibers. Moreover, p-RPS6Ser240/244 intensity within paxillin-positive regions, a marker of focal adhesion complexes, was elevated at 120 min irrespective of stimulus ( P = 0.006) before returning to PRE at 300 min. These data confirm that RPS6Ser240/244 phosphorylation occurs in the region of human muscle fibers to which mTOR translocates following anabolic stimuli and identifies focal adhesion complexes as a potential site of mTORC1 regulation in vivo.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0773e32cf8569831d8f3f24029e16447Test
https://doi.org/10.1152/ajpcell.00357.2021Test

7

Pancreatic beta cell autophagy is impaired in type 1 diabetes

المؤلفون: Amelia K. Linnemann, Charanya Muralidharan, Abass M. Conteh, Pascal de Boer, Jeroen Kuipers, Michelle Marasco, Justin J. Crowder

المصدر: Diabetologia, 64(4), 865-877. SPRINGER
Diabetologia

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Autophagosome, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Autophagy-Related Proteins, Nod, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Mice, Inbred NOD, Insulin-Secreting Cells, Internal medicine, Diabetes mellitus, Macroautophagy, Internal Medicine, medicine, Autophagy, Animals, Humans, NOD mice, Proinsulin, Type 1 diabetes, business.industry, Autoantibody-positive, medicine.disease, Lysosome, Disease Models, Animal, Diabetes Mellitus, Type 1, 030104 developmental biology, Endocrinology, Crinophagy, Case-Control Studies, Female, Beta cell, Lysosomes, business, 030217 neurology & neurosurgery, Signal Transduction

الوصف: Aims/hypothesis Pancreatic beta cells are subjected to exogenous damaging factors such as proinflammatory cytokines or excess glucose that can cause accumulation of damage-inducing reactive oxygen species during the pathogenesis of diabetes. We and others have shown that beta cell autophagy can reduce reactive oxygen species to protect against apoptosis. While impaired islet autophagy has been demonstrated in human type 2 diabetes, it is unknown if islet autophagy is perturbed in the pathogenesis of type 1 diabetes. We hypothesised that beta cell autophagy is dysfunctional in type 1 diabetes, and that there is a progressive loss during early diabetes development. Methods Pancreases were collected from chloroquine-injected and non-injected non-obese diabetes-resistant (NOR) and non-obese diabetic (NOD) mice. Age- and BMI-matched pancreas tissue sections from human organ donors (N = 34) were obtained from the Network for Pancreatic Organ Donors with Diabetes (nPOD). Tissue sections were stained with antibodies against proinsulin or insulin (beta cell markers), microtubule-associated protein 1 light chain 3 A/B (LC3A/B; autophagosome marker), lysosomal-associated membrane protein 1 (LAMP1; lysosome marker) and p62 (autophagy adaptor). Images collected on a scanning laser confocal microscope were analysed with CellProfiler and ImageJ. Secondary lysosomes and telolysosomes were assessed in electron micrographs of human pancreatic tissue sections (n = 12), and energy dispersive x-ray analysis was performed to assess distribution of elements (n = 5). Results We observed increased autophagosome numbers in islets of diabetic NOD mice (p = 0.008) and increased p62 in islets of both non-diabetic and diabetic NOD mice (p p p p = 0.003) and non-diabetic NOD mice (p p p p p = 0.002). Conclusions/interpretation We provide evidence of islet macroautophagy/crinophagy impairment in human type 1 diabetes. We also document accumulation of telolysosomes with peripheral nitrogen in beta cells of autoantibody-positive donors, demonstrating altered lysosome content that may be associated with lysosome dysfunction before clinical hyperglycaemia. Similar macroautophagy impairments are present in the NOD mouse model of type 1 diabetes. Graphical abstract

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aca8a2e71e6e61e43eb7bea2f3d7a3e4Test
https://doi.org/10.1007/s00125-021-05387-6Test

8

Separating insulin-mediated and non-insulin-mediated glucose uptake during and after aerobic exercise in type 1 diabetes

المؤلفون: Thanh-Tin P. Nguyen, Jessica R. Castle, Peter G. Jacobs, Michael C. Riddell, Kerry S. Kuehl, Joseph El Youssef, Deborah Branigan, Ahmad Haidar, Florian H. Guillot, Leah M. Wilson, Virginia Gabo

المصدر: Am J Physiol Endocrinol Metab

الوصف: Aerobic exercise in type 1 diabetes (T1D) causes rapid increase in glucose utilization due to muscle work during exercise, followed by increased insulin sensitivity after exercise. Better understanding of these changes is necessary for models of exercise in T1D. Twenty-six individuals with T1D underwent three sessions at three insulin rates (100%, 150%, 300% of basal). After 3-h run-in, participants performed 45 min aerobic exercise (moderate or intense). We determined area under the curve for endogenous glucose production (AUC(EGP)) and rate of glucose disappearance (AUC(Rd)) over 45 min from exercise start. A novel application of linear regression of R(d) across the three insulin sessions allowed separation of insulin-mediated from non-insulin-mediated glucose uptake before, during, and after exercise. AUC(Rd) increased 12.45 mmol/L (CI = 10.33–14.58, P < 0.001) and 13.13 mmol/L (CI = 11.01–15.26, P < 0.001) whereas AUC(EGP) increased 1.66 mmol/L (CI = 1.01–2.31, P < 0.001) and 3.46 mmol/L (CI = 2.81–4.11, P < 0.001) above baseline during moderate and intense exercise, respectively. AUC(EGP) increased during intense exercise by 2.14 mmol/L (CI = 0.91–3.37, P < 0.001) compared with moderate exercise. There was significant effect of insulin infusion rate on AUC(Rd) equal to 0.06 mmol/L per % above basal rate (CI = 0.05–0.07, P < 0.001). Insulin-mediated glucose uptake rose during exercise and persisted hours afterward, whereas non-insulin-mediated effect was limited to the exercise period. To our knowledge, this method of isolating dynamic insulin- and non-insulin-mediated uptake has not been previously employed during exercise. These results will be useful in informing glucoregulatory models of T1D. The study has been registered at www.clinicaltrials.gov as NCT03090451. NEW & NOTEWORTHY Separating insulin and non-insulin glucose uptake dynamically during exercise in type 1 diabetes has not been done before. We use a multistep process, including a previously described linear regression method, over three insulin infusion sessions, to perform this separation and can graph these components before, during, and after exercise for the first time.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2498af9d2d8494887b23717a316bf729Test
https://doi.org/10.1152/ajpendo.00534.2020Test

9

Association of protein tyrosine phosphatase 1B gene polymorphism with the effects of weight reduction therapy on bodyweight and glycolipid profiles in obese patients

المؤلفون: Yoshihiro Miyamoto, Hiroko Morisaki, Kazuya Muranaka, Kikuko Hotta, Takayuki Morisaki, Noriko Satoh-Asahara, Yousuke Konishi, Hajime Yamakage

المصدر: Journal of Diabetes Investigation, Vol 12, Iss 8, Pp 1462-1470 (2021)
Journal of Diabetes Investigation

مصطلحات موضوعية: Male, Endocrinology, Diabetes and Metabolism, 030204 cardiovascular system & hematology, Body Mass Index, Cohort Studies, 0302 clinical medicine, Japan, Weight loss, Prospective Studies, Prospective cohort study, Weight reduction therapy, Protein Tyrosine Phosphatase, Non-Receptor Type 1, education.field_of_study, Protein tyrosine phosphatase 1B, General Medicine, Articles, Middle Aged, Clinical Science and Care, Original Article, Female, medicine.symptom, Waist Circumference, Adult, medicine.medical_specialty, Waist, Population, 030209 endocrinology & metabolism, Polymorphism, Single Nucleotide, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Weight Loss, Internal Medicine, medicine, Humans, Obesity, education, Life Style, Alleles, Aged, Polymorphism, Genetic, business.industry, Body Weight, medicine.disease, RC648-665, Endocrinology, Gene polymorphism, Glycolipids, business, Energy Metabolism, Body mass index

الوصف: Aims/Introduction Weight reduction therapy is the primary treatment to prevent complications of obesity, such as lifestyle diseases and cardiovascular disease; however, to date, useful methods and genetic factors for predicting the outcomes of weight reduction therapy in obese patients have not been established. Protein tyrosine phosphatase 1B (PTP1B), a negative regulator for insulin and leptin signaling, potentially modulates glucose and energy homeostasis. This study aimed to investigate the contribution of PTPN1 polymorphisms on weight reduction and diabetes in obese Japanese patients. Materials and Methods PTPN1‐tagged single‐nucleotide polymorphisms (SNPs) rs3787348 and rs6067484 were genotyped in 447 obese Japanese patients from the general population. In this prospective cohort study, all obese patients underwent a 3‐month weight reduction therapy with lifestyle modifications, as recommended by guidelines. Results In obese patients (male/female 196/251, age 50 ± 15 years, body mass index [BMI] 32 ± 6 kg/m2), the minor allele appeared at a frequency of 45.5% in rs3787348 SNP of the PTPN1 gene. The T allele of rs3787348 was significantly associated with a higher BMI (P = 0.041 in the additive model). The patients with the T allele in SNP rs3787348 of PTPN1 had significantly smaller reductions in BMI, bodyweight and waist circumference levels during weight reduction therapy (BMI G/G, −1.9 ± 0.2; G/T, −1.5 ± 0.1; T/T, −1.2 ± 0.1; P = 0.001 in the additive model). Conclusions Our findings show that the SNP rs3787348 in PTPN1 was associated with the effects of weight reduction therapy on BMI and waist circumference among obese Japanese patients.
Protein tyrosine phosphatase 1B negatively regulates insulin and leptin signaling. The rs3787348 in PTPN1 was associated with the effects of weight reduction therapy. The single‐nucleotide polymorphism of PTPN1 might predict the efficacy of weight reduction in obese patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d5f8847344172785eb3cdd8f9ad787dcTest
https://doaj.org/article/3ac3560632e64164bdc41c46f81b08e8Test

10

Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans

المؤلفون: Chin Wong, Thomas Gelzleichter, Junichiro Sonoda, Amos Baruch, Linda Morrow, Suresh Dheerendra, Leslie W. Chinn, Richard Boismenu, Eric Wakshull, Maria E. Wilson, Puneet S. Arora, Shan Chen, Anjali Vaze, Johnny Gutierrez, Nicholas Lewin-Koh

المصدر: Proceedings of the National Academy of Sciences of the United States of America

مصطلحات موضوعية: Male, 0301 basic medicine, obesity, Medical Sciences, FGF21, Adipose tissue, Mice, 0302 clinical medicine, Weight loss, Homeostasis, Medicine, Multidisciplinary, biology, Middle Aged, Biological Sciences, Adipose Tissue, Female, Adiponectin, Antibody, medicine.symptom, FGF21 receptor activation, Adult, Agonist, medicine.medical_specialty, Adolescent, medicine.drug_class, 030209 endocrinology & metabolism, Antibodies, Food Preferences, Young Adult, 03 medical and health sciences, Internal medicine, Weight Loss, Animals, Humans, Receptor, Fibroblast Growth Factor, Type 1, Aged, business.industry, Fibroblast growth factor receptor 1, Body Weight, medicine.disease, Obesity, Fibroblast Growth Factors, stomatognathic diseases, Macaca fascicularis, 030104 developmental biology, Endocrinology, biology.protein, food preference, business, metabolism, Biomarkers

الوصف: Significance Fibroblast growth factor 21 (FGF21) controls metabolic organ homeostasis and eating behavior via FGF receptor 1/Klothoβ (FGFR1/KLB) complexes. Here we show that a bispecific anti-FGFR1/KLB agonist antibody, BFKB8488A, mimics the actions of FGF21 in monkeys and humans. BFKB8488A induced marked weight loss in obese monkeys while elevating expression of FGFR1 target genes in adipose tissue. A clinical study in overweight human participants demonstrated that a single dose of BFKB8488A caused transient body weight reduction, sustained improvement in cardiometabolic parameters, and a trend toward reduction in preference for sweet taste and carbohydrate intake. These data suggest that antibody-mediated activation of the FGFR1/KLB complex in humans recapitulates the effects of FGF21 and can be used as therapy for obesity-related metabolic defects.
Fibroblast growth factor 21 (FGF21) controls metabolic organ homeostasis and eating/drinking behavior via FGF receptor 1/Klothoβ (FGFR1/KLB) complexes expressed in adipocytes, pancreatic acinar cells, and the nervous system in mice. Chronic administration of recombinant FGF21 or engineered variants improves metabolic health in rodents, nonhuman primates, and humans; however, the rapid turnover of these molecules limits therapeutic utility. Here we show that the bispecific anti-FGFR1/KLB agonist antibody BFKB8488A induced marked weight loss in obese cynomolgus monkeys while elevating serum adiponectin and the adipose expression of FGFR1 target genes, demonstrating its action as an FGF21 mimetic. In a randomized, placebo-controlled, single ascending-dose study in overweight/obese human participants, subcutaneous BFKB8488A injection caused transient body weight reduction, sustained improvement in cardiometabolic parameters, and a trend toward reduction in preference for sweet taste and carbohydrate intake. These data suggest that specific activation of the FGFR1/KLB complex in humans can be used as therapy for obesity-related metabolic defects.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ecb1e6fc5999a3fd66bc3ad16e368b18Test
https://doi.org/10.1073/pnas.2012073117Test

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