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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(1): 63-70, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35048602

RESUMO

Objective: To study the role of M2 macrophage-derived exosomes (M2-exo) in osteogenic differentiation and Hedgehog signaling pathway of mouse bone marrow mesenchymal stem cells (BMSCs) under in vitro high-glucose and high-insulin conditions. Methods: RAW 264.7 cells were induced toward M2 macrophage polarization and then M2-exo were extracted and identified. Immunofluorescence assay was performed to detect the internalization of M2-exo by BMSCs. BMSCs were divided into the normal control group (Control group), the high-glucose and high-insulin group (HGI group), and the HGI with M2-exo intervention group (HGI+M2e group). BMSCs in the Control group were cultured in osteogenic inductive medium with 5.5 mmol/L glucose, but no insulin or M2-exo. BMSCs in the HGI group were cultured in osteogenic inductive medium with 25 mmol/L glucose and 174 nmol/L insulin. BMSCs in the HGI+M2e group were cultured in the same medium as that of the HGI group, with the additional treatment of 6, 30, 60 µg/mL M2-exo, respectively. After osteogenic induction for 7 days and 14 days, alkaline phosphatase (ALP) staining and alizarin red staining were performed respectively to assess the osteogenic differentiation potential of BMSCs from different groups. In addition, BMSCs in the Control group, HGI group, and HGI+M2e group treated with 30 µg/mL M2-exo were examined with qPCR after osteogenic induction for 14 days and Western blot after osteogenic induction for 21 days to assess the osteogenesis and the expression of Hedgehog pathway-related genes and proteins. Results: M2 macrophage polarization was induced successfully, with highly positive expression of CD206, the M2 polarization surface marker. The M2-exo had the typical structure of round or oval-shaped bilayered-membrane vesicles. The diameter distribution of M2-exo ranged from 50 to 125 nm (accounting for 99.14% of all M2-exo). M2-exo samples showed positive expression of exosomal markers CD9, CD63 and CD81 proteins. Immunofluorescence staining showed that M2-exo were taken up and internalized by BMSCs. After osteogenic induction for 7 days, the ALP activity of BMSCs in the HGI group was lower than that of the Control group. After interventions of 6 µg/mL, 30 µg/mL, and 60 µg/mL M2-exo, the ALP activity of the HGI+M2-exo group was significantly increased compared with that of the HGI group ( P<0.05). After osteogenic induction for 14 days, the number of mineralized nodules in the HGI group was lower than that in the Control group, and after intervention, only the HGI+M2e group treated with 30 µg/mL M2-exo showed higher level of mineralization than that in the HGI group ( P<0.05). qPCR analysis revealed that the expression levels of the osteogenesis-related genes, including Runx2, Alp and Ocn, and Hedgehog pathway-related genes, including Gli1, Smo and Ptch1, were downregulated in the HGI group, all being lower than those of the Control group to varying degrees, while 30 µg/mL M2-exo treatment could promote the up-regulation of these genes, showing significant difference in comparison with their expression levels in the HGI group ( P<0.05). In addition, Western blot analysis showed that the expression of the osteogenesis-related proteins, including RUNX2 and COL1A1, and GLI1, the Hedgehog signaling pathway protein, was down-regulated in the HGI group, while the expression of COL1A1 and GLI1 was up-regulated after 30 µg/mL M2-exo treatment, showing significant difference when compared with that of the HGI group ( P<0.05). Conclusion: High glucose and high insulin had inhibitory effect on the osteogenic differentiation potential of BMSCs. After intervention with M2-exo, the Hedgehog signaling pathway in BMSCs was activated and the osteogenic differentiation potential was enhanced, suggesting that M2-exo might have therapeutic potentials for the treatment of diabetic bone disease.


Assuntos
Exossomos , Insulinas , Células-Tronco Mesenquimais , Animais , Células da Medula Óssea , Diferenciação Celular , Células Cultivadas , Glucose , Proteínas Hedgehog , Macrófagos , Camundongos , Osteogênese
2.
Appetite ; 168: 105750, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34648911

RESUMO

OBJECTIVES: The objective of this study was to evaluate the relationship between food intake and serum levels of leptin and ghrelin in the luteal (LP) and follicular (FP) phases of the MC (menstrual cycle) in participants with and without PMS (premenstrual syndrome). METHODS: This was a case-control study with healthy participants aged 20-45 years with regular menstrual cycles (24-35 days) with and without PMS. After the Daily Record of Severity of Problems (DRSP) was filled out for two months (PMS diagnosis), a nutritional assessment was carried out based on twelve food intake records (for two menstrual cycles) to quantify food intake. RESULTS: Of the 69 participants analyzed, 35 experienced PMS and 34 did not experience PMS. For participants with PMS, calorie and carbohydrate intake was higher during LP than in FP (p = 0.004 and p = 0.003, respectively), whereas these changes were not observed in participants without PMS (p > 0.05). There were interactions between the groups and the MC phases (LP and FP) for the intake of calories (p = 0.028) and carbohydrates (p = 0.001). There was a marginal negative relationship between the levels of ghrelin and calorie intake in FP (rS = -0.314, p = 0.066) in the PMS group and a negative relationship between the levels of ghrelin and leptin in LP (rS = -0.490, p = 0.004) in the group without PMS. CONCLUSIONS: These results indicated a higher calorie and carbohydrate intake during LP in participants with PMS, in addition to the hypothesis that the roles of ghrelin and leptin in energy regulation may be different in participants with PMS compared to those without PMS.


Assuntos
Insulinas , Síndrome Pré-Menstrual , Estudos de Casos e Controles , Ingestão de Alimentos , Feminino , Grelina , Humanos , Leptina
3.
Talanta ; 238(Pt 1): 122947, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34857352

RESUMO

An ultrasensitive novel electrochemical nano-biosensor for rapid detection of insulin antibodies against diabetes antigens was developed in this research. The presence of insulin antibodies has been demonstrated to be a strong predictor for the development of type 1 diabetes in individuals who do not have diabetes but are genetically predisposed. The proposed nano-biosensor fabrication process was based on the optimized sequential electropolymerization of polyaniline and electrodeposition of gold nanoparticles on the surface of the functionalized gold electrode. The morphological and chemical characterization of the modified electrode was studied by field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and micro Raman spectroscopy. Moreover, the role of each component in the modification of the electrode was studied by electrochemical methods systematically. After immobilizing insulin antigen and blocking with bovine serum albumin, the nano-biosensor was used for determining different concentrations of insulin antibody under the optimal conditions. This nano-biosensor could respond to insulin antibody with a linear calibration range from 0.001 ng ml-1 to 1000 ng ml-1 with the detection limit of 0.017 pg ml-1 and 0.034 pg ml-1 and selectivity of 18.544 µA ng-1 ml.cm-2 and 31.808 µA ng-1 ml.cm-2 via differential pulse voltammetry and square wave voltammetry, respectively. This novel nano-biosensor exhibited a short response time, high sensitivity, and good reproducibility. It was successfully used in determining the insulin antibody in human samples with a standard error of less than 0.178. Therefore, the nano-biosensor has the potential for the application of early detection of type 1 diabetes. To our best knowledge, label-free electrochemical detection of insulin antibody based on immunosensor is developed for the first time.


Assuntos
Técnicas Biossensoriais , Insulinas , Nanopartículas Metálicas , Técnicas Eletroquímicas , Eletrodos , Ouro , Humanos , Imunoensaio , Anticorpos Anti-Insulina , Limite de Detecção , Reprodutibilidade dos Testes
6.
Nat Commun ; 12(1): 6185, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702819

RESUMO

The circadian system cyclically regulates many physiological and behavioral processes within the day. Desynchronization between physiological and behavioral rhythms increases the risk of developing some, including metabolic, disorders. Here we investigate how the oscillatory nature of metabolic signals, resembling feeding-fasting cycles, sustains the cell-autonomous clock in peripheral tissues. By controlling the timing, period and frequency of glucose and insulin signals via microfluidics, we find a strong effect on Per2::Luc fibroblasts entrainment. We show that the circadian Per2 expression is better sustained via a 24 h period and 12 h:12 h frequency-encoded metabolic stimulation applied for 3 daily cycles, aligned to the cell-autonomous clock, entraining the expression of hundreds of genes mostly belonging to circadian rhythms and cell cycle pathways. On the contrary misaligned feeding-fasting cycles synchronize and amplify the expression of extracellular matrix-associated genes, aligned during the light phase. This study underlines the role of the synchronicity between life-style-associated metabolic signals and peripheral clocks on the circadian entrainment.


Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano/genética , Comportamento Alimentar/fisiologia , Animais , Ciclo Celular/genética , Linhagem Celular , Relógios Circadianos/genética , Meios de Cultura/metabolismo , Matriz Extracelular/genética , Jejum/fisiologia , Glucose/metabolismo , Insulinas/metabolismo , Dispositivos Lab-On-A-Chip , Camundongos , Proteínas Circadianas Period/genética , Transcriptoma
7.
Diabetes Metab J ; 45(5): 629-640, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34610718

RESUMO

The year 2021 marks the 100th anniversary of the discovery of insulin, which has greatly changed the lives of people with diabetes and become a cornerstone of advances in medical science. A rapid bench-to-bedside application of the lifesaving pancreatic extract and its immediate commercialization was the result of a promising idea, positive drive, perseverance, and collaboration of Banting and colleagues. As one of the very few proteins isolated in a pure form at that time, insulin also played a key role in the development of important methodologies and in the beginning of various fields of modern science. Since its discovery, insulin has evolved continuously to optimize the care of people with diabetes. Since the 1980s, recombinant DNA technology has been employed to engineer insulin analogs by modifying their amino acid sequence, which has resulted in the production of insulins with various profiles that are currently used. However, unmet needs in insulin treatment still exist, and several forms of future insulins are under development. In this review, we discuss the past, present, and future of insulin, including a history of ceaseless innovations and collective intelligence. We believe that this story will be a solid foundation and an unerring guide for the future.


Assuntos
Diabetes Mellitus , Insulinas , Sequência de Aminoácidos , Diabetes Mellitus/tratamento farmacológico , Humanos , Insulina/uso terapêutico , Insulina Regular Humana
8.
J Dairy Sci ; 104(12): 12616-12627, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34538499

RESUMO

Our objective was to determine whether abomasal infusions of increasing doses of oleic acid (cis-9 C18:1; OA) improved fatty acid (FA) digestibility and milk production of lactating dairy cows. Eight rumen-cannulated multiparous Holstein cows (138 d in milk ± 52) were randomly assigned to treatment sequence in a replicated 4 × 4 Latin square design with 18-d periods consisting of 7 d of washout and 11 d of infusion. Production and digestibility data were collected during the last 4 d of each infusion period. Treatments were 0, 20, 40, or 60 g/d of OA. We dissolved OA in ethanol before infusions. The infusate solution was divided into 4 equal infusions per day, occurring every 6 h, delivering the daily cis-9 C18:1 for each treatment. Animals received the same diet throughout the study, which contained (percent diet dry matter) 28% neutral detergent fiber, 17% crude protein, 27% starch, and 3.3% FA (including 1.8% FA from a saturated FA supplement containing 32% C16:0 and 52% C18:0). Infusion of OA did not affect intake or digestibility of dry matter and neutral detergent fiber. Increasing OA from 0 to 60 g/d linearly increased the digestibility of total FA (8.40 percentage units), 16-carbon FA (8.30 percentage units), and 18-carbon FA (8.60 percentage units). Therefore, increasing OA linearly increased absorbed total FA (162 g/d), 16-carbon FA (26.0 g/d), and 18-carbon FA (127 g/d). Increasing OA linearly increased milk yield (4.30 kg/d), milk fat yield (0.10 kg/d), milk lactose yield (0.22 kg/d), 3.5% fat-corrected milk (3.90 kg/d), and energy-corrected milk (3.70 kg/d) and tended to increase milk protein yield. Increasing OA did not affect the yield of mixed milk FA but increased yield of preformed milk FA (65.0 g/d) and tended to increase the yield of de novo milk FA. Increasing OA quadratically increased plasma insulin concentration with an increase of 0.18 µg/L at 40 g/d OA, and linearly increased the content of cis-9 C18:1 in plasma triglycerides by 2.82 g/100 g. In conclusion, OA infusion increased FA digestibility and absorption, milk fat yield, and circulating insulin without negatively affecting dry matter intake. In our short-term infusion study, most of the digestion and production measurements responded linearly, indicating that 60 g/d OA was the best dose. Because a quadratic response was not observed, improvements in FA digestibility and production might continue with higher doses of OA, which deserves further attention.


Assuntos
Ácidos Graxos , Insulinas , Ração Animal/análise , Animais , Bovinos , Dieta/veterinária , Suplementos Nutricionais , Digestão , Feminino , Lactação , Ácido Oleico , Ácido Palmítico
9.
Theriogenology ; 175: 100-110, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34534687

RESUMO

The role of anti-Müllerian hormone (AMH) and insulin-like peptide 3 (INSL3) in male infertility is not fully understood. We used the downregulated testis as a model of gonadotropin-dependent infertility. Serum testosterone and AMH concentrations were studied in five adult male Beagles implanted (day 0) with 4.7 mg deslorelin (Suprelorin®, Virbac) (DES group). Testicular expression of LH receptor (LHR) and androgen receptor (AR), AMH, type 2 AMH receptor (AMHR2), INSL3 and its receptor (RXFP2) was evaluated 112 days (16 weeks) after deslorelin treatment by qPCR and immunohistochemistry, and compared to untreated adult (CON, n = 6) and prepubertal (PRE, n = 8) dogs. Serum testosterone concentration decreased significantly by the onset of aspermia on study day 14 (four dogs) or day 21 (one dog), and was baseline on day 105 (week 15). In contrast, serum AMH started to increase only after the onset of aspermia and reached the maximum detectable concentration of the assay by day 49-105 in individual dogs. Testicular LHR gene expression in DES was lower than in CON and PRE (P < 0.0001), while AR gene expression in DES was similar to CON and significantly higher than PRE (P < 0.0001). Testicular AMH expression in DES was intermediate compared to the lowest mRNA levels found in CON and the highest in PRE (P ≤ 0.006). AMHR2 gene expression was similar between groups. AMH protein was detected in Sertoli cells only, while AMHR2 immunoreactivity was principally detected in Leydig cells which appeared to be increased in DES. INSL3 and RXFP2 gene expression was significantly downregulated in the DES testis along with noticeably weak Leydig cell immunosignals compared to CON. In conclusion, deslorelin treatment caused testicular LH insensitivity without affecting androgen sensitivity, and de-differentiation of Sertoli and Leydig cells. In DES, upregulation of the AMH-AMHR2 feed-back loop and downregulation of the INSL3-RXFP2 feed-forward loop are paracrine-autocrine mechanisms that may additionally regulate testosterone production independent of gonadotropins. Our results support AMH and INSL3 as unique biomarkers and paracrine-autocrine regulators of testis function involved in the intimate interplay between Sertoli and Leydig cells.


Assuntos
Hormônio Antimülleriano , Insulina , Insulinas , Células Intersticiais do Testículo , Proteínas , Testículo/efeitos dos fármacos , Testosterona , Animais , Hormônio Antimülleriano/genética , Hormônio Antimülleriano/metabolismo , Biomarcadores , Cães , Regulação para Baixo , Insulina/genética , Insulina/metabolismo , Células Intersticiais do Testículo/metabolismo , Masculino , Peptídeos , Proteínas/genética , Proteínas/metabolismo , Testículo/metabolismo , Pamoato de Triptorrelina/análogos & derivados
10.
Elife ; 102021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34403334

RESUMO

To investigate the role of the vasculature in pancreatic ß-cell regeneration, we crossed a zebrafish ß-cell ablation model into the avascular npas4l mutant (i.e. cloche). Surprisingly, ß-cell regeneration increased markedly in npas4l mutants owing to the ectopic differentiation of ß-cells in the mesenchyme, a phenotype not previously reported in any models. The ectopic ß-cells expressed endocrine markers of pancreatic ß-cells, and also responded to glucose with increased calcium influx. Through lineage tracing, we determined that the vast majority of these ectopic ß-cells has a mesodermal origin. Notably, ectopic ß-cells were found in npas4l mutants as well as following knockdown of the endothelial/myeloid determinant Etsrp. Together, these data indicate that under the perturbation of endothelial/myeloid specification, mesodermal cells possess a remarkable plasticity enabling them to form ß-cells, which are normally endodermal in origin. Understanding the restriction of this differentiation plasticity will help exploit an alternative source for ß-cell regeneration.


Assuntos
Diferenciação Celular , Células Secretoras de Insulina/fisiologia , Mesoderma/embriologia , Regeneração , Peixe-Zebra/embriologia , Animais , Endotélio/fisiologia , Insulinas/metabolismo , Peixe-Zebra/fisiologia
11.
Sci Rep ; 11(1): 17395, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34462500

RESUMO

Prolonged periods of forced social isolation is detrimental to well-being, yet we know little about which genes regulate susceptibility to its effects. In the fruit fly, Drosophila melanogaster, social isolation induces stark changes in behavior including increased aggression, locomotor activity, and resistance to ethanol sedation. To identify genes regulating sensitivity to isolation, I screened a collection of sixteen hundred P-element insertion lines for mutants with abnormal levels of all three isolation-induced behaviors. The screen identified three mutants whose affected genes are likely central to regulating the effects of isolation in flies. One mutant, sex pistol (sxp), became extremely aggressive and resistant to ethanol sedation when socially isolated. sxp also had a high level of male-male courtship. The mutation in sxp reduced the expression of two minor isoforms of the actin regulator hts (adducin), as well as mildly reducing expression of CalpA, a calcium-dependent protease. As a consequence, sxp also had increased expression of the insulin-like peptide, dILP5. Analysis of the social behavior of sxp suggests that these minor hts isoforms function to limit isolation-induced aggression, while chronically high levels of dILP5 increase male-male courtship.


Assuntos
Proteínas de Drosophila/genética , Drosophila/fisiologia , Isolamento Social , Agressão , Animais , Proteínas de Ligação a Calmodulina/genética , Proteínas de Ligação a Calmodulina/metabolismo , Calpaína/genética , Calpaína/metabolismo , Corte , Regulação para Baixo , Drosophila/genética , Proteínas de Drosophila/metabolismo , Insulinas/genética , Insulinas/metabolismo , Locomoção , Masculino , Mutação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Regulação para Cima
13.
Science ; 373(6554): 522-527, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34326234

RESUMO

Despite innovations in insulin therapy since its discovery, most patients living with type 1 diabetes do not achieve sufficient glycemic control to prevent complications, and they experience hypoglycemia, weight gain, and major self-care burden. Promising pharmacological advances in insulin therapy include the refinement of extremely rapid insulin analogs, alternate insulin-delivery routes, liver-selective insulins, add-on drugs that enhance insulin effect, and glucose-responsive insulin molecules. The greatest future impact will come from combining these pharmacological solutions with existing automated insulin delivery methods that integrate insulin pumps and glucose sensors. These systems will use algorithms enhanced by machine learning, supplemented by technologies that include activity monitors and sensors for other key metabolites such as ketones. The future challenges facing clinicians and researchers will be those of access and broad clinical implementation.


Assuntos
Automonitorização da Glicemia , Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Controle Glicêmico , Hipoglicemiantes/uso terapêutico , Insulinas/uso terapêutico , Absorção Fisiológica , Algoritmos , Automação , Diabetes Mellitus Tipo 1/sangue , Humanos , Sistemas de Infusão de Insulina , Insulinas/administração & dosagem , Insulinas/sangue , Insulinas/farmacocinética , Refeições
15.
J Dairy Sci ; 104(10): 11306-11316, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34275626

RESUMO

Trans-10,cis-12 conjugated linoleic acid (t10,c12 CLA) is well recognized as a key CLA isomer responsible for the reduction in milk fat synthesis that leads to milk fat depression in dairy cows. Sterol regulatory element binding protein-1 (SREBP1) is a key transcription factor in bovine mammary gland coordinating transcription of the genes for fatty acid synthesis. SREBP1 activation requires the removal of insulin-induced gene-1 (Insig1) that serves as a repressor of SREBP1 in the endoplasmic reticulum (ER). We hypothesized that t10,c12 CLA reduced SREBP1 activation by delaying Insig1 degradation. In the present study, we used undifferentiated bovine mammary epithelial cells (MAC-T cells) and treated them with t10,c12 CLA for 6 h. We found that SREBP1 protein expression declined over 56% when cells were treated with 60 µM or greater concentration of t10,c12 CLA. Such inhibitory effects were also observed in the mRNA expression of SREBP1-regulated genes including SREBP1, fatty acid synthetase, stearoyl-CoA desaturase, and Insig1. Compared with no CLA group, 60 µM or higher concentration of t10,c12 CLA increased Insig1 protein expression over 2-fold in cells transfected with FLAG-tagged Insig1. This stimulatory effect was not specific to t10,c12 CLA but also other polyunsaturated fatty acids including cis-9,trans-11 CLA and linoleic acid. Oleic acid had no effect on Insig1 protein expression, whereas palmitic acid decreased Insig1 protein expression. Further investigation revealed that increased abundance of FLAG-Insig1 with t10,c12 CLA was due to the inhibition of the proteasomal degradation of Insig1. The t10,c12 CLA delayed the Insig1 decay when protein synthesis was blocked. Immunoprecipitation also confirmed that the interaction between ubiquitin-like domain-containing protein 8 and Insig1, the key step of removing Insig1 from ER and freeing SREBP1 for proteolytic processing, was inhibited by t10,c12 CLA, but not palmitic acid. These findings suggested that t10,c12 CLA played a role in regulating SREBP1 activation by reducing proteasomal degradation of Insig1. We concluded that stabilized Insig1 retained SREBP1 in the ER from activation, thus reducing lipogenic gene transcription.


Assuntos
Insulinas , Ácidos Linoleicos Conjugados , Animais , Bovinos , Células Epiteliais , Ácidos Graxos , Feminino , Ácidos Linoleicos Conjugados/farmacologia , Glândulas Mamárias Animais , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
16.
Sci Transl Med ; 13(596)2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078744

RESUMO

Transplantation of stem cell-derived ß (SC-ß) cells represents a promising therapy for type 1 diabetes (T1D). However, the delivery, maintenance, and retrieval of these cells remain a challenge. Here, we report the design of a safe and functional device composed of a highly porous, durable nanofibrous skin and an immunoprotective hydrogel core. The device consists of electrospun medical-grade thermoplastic silicone-polycarbonate-urethane and is soft but tough (~15 megapascal at a rupture strain of >2). Tuning the nanofiber size to less than ~500 nanometers prevented cell penetration while maintaining maximum mass transfer and decreased cellular overgrowth on blank (cell-free) devices to as low as a single-cell layer (~3 micrometers thick) when implanted in the peritoneal cavity of mice. We confirmed device safety, indicated as continuous containment of proliferative cells within the device for 5 months. Encapsulating syngeneic, allogeneic, or xenogeneic rodent islets within the device corrected chemically induced diabetes in mice and cells remained functional for up to 200 days. The function of human SC-ß cells was supported by the device, and it reversed diabetes within 1 week of implantation in immunodeficient and immunocompetent mice, for up to 120 and 60 days, respectively. We demonstrated the scalability and retrievability of the device in dogs and observed viable human SC-ß cells despite xenogeneic immune responses. The nanofibrous device design may therefore provide a translatable solution to the balance between safety and functionality in developing stem cell-based therapies for T1D.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Insulinas , Transplante das Ilhotas Pancreáticas , Nanofibras , Animais , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 1/terapia , Cães , Insulina , Camundongos
18.
Obes Res Clin Pract ; 15(4): 362-367, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34148808

RESUMO

BACKGROUND: The present study aimed to evaluate whether mothers with obesity/central obesity and metabolic syndrome before gestation are at higher risk of insulin administration in gestational diabetes mellitus (GDM) to diminish the burden of insulin use during pregnancy. METHODS: This was a population-based retrospective cohort study conducted using data from the National Health Information Database of Korea. We identified all deliveries from January 1, 2011 to December 31, 2015 (N = 1,214,655). Among the deliveries, we identified mothers with pre-pregnancy health checkup records and without previous diabetes history (N = 325,208). Hazards of insulin use in GDM were calculated based on pre-pregnancy obesity/central obesity and metabolic syndrome. RESULTS: Hazards of insulin use in GDM increased proportionately with an increase in the pre-pregnancy body mass index (BMI) and waist circumference (WC). After the adjustment for clinical factors, high BMI group (≥30 kg/m2) and high WC group (≥100 cm) were significantly associated with higher hazard ratios (HRs) (HR 4.161, 95% Confidence interval [CI] 3.381-5.121, P < 0.001 and HR 2.563, 95% CI 1.769-3.712, P < 0.001, respectively). The presence of pre-pregnancy metabolic syndrome significantly increased the hazard of insulin use in GDM (0.54% vs. 5.04%). In the presence of obesity (BMI ≥ 25 kg/m2) or central obesity (WC ≥ 85 cm), HRs of insulin use in GDM were 2.637 (95% CI 2.275-3.056) and 1.603 (95% CI 1.023-2.511), respectively, after adjustment for clinical factors. CONCLUSIONS: The presence of pre-pregnancy obesity/central obesity and metabolic syndrome in Korean mothers is associated with increased risk of insulin use in GDM.


Assuntos
Diabetes Gestacional , Insulinas , Síndrome Metabólica , Índice de Massa Corporal , Estudos de Coortes , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/epidemiologia , Gravidez , Estudos Retrospectivos , Fatores de Risco
19.
Circ Heart Fail ; 14(6): e008075, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34129365

RESUMO

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) and insulin-treated diabetes have a high risk of cardiovascular complications. Mineralocorticoid receptor antagonists may mitigate this risk. We aim to explore the effect of eplerenone on cardiovascular outcomes and all-cause mortality in HFrEF patients with diabetes, including those treated with insulin in the EMPHASIS-HF trial (Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms). METHODS: The primary outcome was the composite of heart failure hospitalization or cardiovascular death. Cox models with treatment-by-diabetes subgroup interaction terms were used. RESULTS: The median follow-up was 21 (10-33) months. Of the 2737 patients included, 623 (23%) had non-insulin-treated diabetes, 236 (9%) had insulin-treated diabetes and 1878 did not have diabetes. Patients with insulin-treated diabetes were younger, more often women, with higher body mass index, waist circumference, more frequent ischemic heart failure cause, impaired kidney function, and longer diabetes duration. Compared with patients without diabetes, those with insulin-treated diabetes had a 2-fold higher risk of having a primary outcome event. The hazard ratio (95% CI) for the effect of eplerenone, compared with placebo, on the primary outcome was 0.31 (0.19-0.50) in insulin-treated diabetes, 0.69 (0.50-0.93) in non-insulin-treated diabetes, and 0.72 (0.58-0.88) in patients without diabetes; interaction P=0.007. The annualized number needed-to-treat-to-benefit with regards to the primary outcome was 3 (95% CI, 3-4) in patients with insulin-treated diabetes, 16 (13-19) in patients with diabetes not receiving insulin, and 26 (24-28) in patients without diabetes. CONCLUSIONS: Patients with insulin-treated diabetes experienced a greater benefit from eplerenone than those with diabetes not treated with insulin and people without diabetes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00232180.


Assuntos
Eplerenona/farmacologia , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Idoso , Diabetes Mellitus/tratamento farmacológico , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca Sistólica/fisiopatologia , Humanos , Insulinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Espironolactona/uso terapêutico , Resultado do Tratamento
20.
J Trace Elem Med Biol ; 67: 126785, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34015661

RESUMO

BACKGROUND & AIMS: Pervious epidemiological evidence on the associations of selenium, zinc with lipid profile and glycemic indices was contradictory. The aim of this study was to investigate whether selenium and zinc were casually associated with lipid profile and glycemic indices using mendelian randomization (MR) analysis. METHOD: A two-sample MR was used to evaluate the causal-effect estimations. Summary statistics for selenium, zinc, lipids and glycemic indices were retrieved from previous large-scale genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) that independently and strongly associated with the selenium and zinc were selected as the instrumental variables. The casual estimates were calculated using inverse variance weighted method (IVW), with weighted median, MR-Egger, and MR-PRESSO test as sensitivity analysis, respectively. RESULTS: In the standard IVW analysis, per SD increment in selenium was associated with an 0.077 mmol/L decrease of TC (95 %CI: -0.102,-0.052) and 0.074 mmol/L of LDL-C (95 %CI: -0.1,-0.048). Suggestive casual associations were found between selenium and insulin or HbA1c. With IVW method, per SD increase in selenium was associated with an 0.023 mmol/L increase of insulin (95 %CI: 0.001,0.045), and an 0.013 mmol/L increase of HbA1c (95 %CI: 0.003,0.023). The results were robust in the sensitivity analysis. Zinc was not casually associated with any of lipid and glycemic markers. CONCLUSION: Our MR analysis provides evidence of the potential causal effect of Se on beneficial lipid profile, including decreased TC and LDL-C. Furthermore, suggestive casual evidence was suggested between Se and increased serum HbA1c levels. Careful consideration is required for the protective effects of Se supplementation. No casual-effect association was found between Zn and any indices of the lipid and glucose parameters.


Assuntos
Selênio/sangue , Colesterol , LDL-Colesterol , Estudo de Associação Genômica Ampla , Hemoglobina A Glicada , Insulinas , Lipídeos , Zinco
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