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BACKGROUND: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM). METHODS: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated. RESULTS: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients. CONCLUSION: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.
Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Glucagon , Teste de Tolerância a Glucose , Condução Nervosa , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Masculino , Pessoa de Meia-Idade , Feminino , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/etiologia , Glucagon/sangue , Estudos Retrospectivos , Glicemia/análise , Condução Nervosa/fisiologia , Idoso , Adulto , Eletromiografia , Células Secretoras de Glucagon , Insulina/sangue , Área Sob a Curva , Fatores de Tempo , Valores de ReferênciaRESUMO
Lifestyle modifications, metformin, and linagliptin reduce the incidence of type 2 diabetes (T2D) in people with prediabetes. The gut microbiota (GM) may enhance such interventions' efficacy. We determined the effect of linagliptin/metformin (LM) vs metformin (M) on GM composition and its relationship to insulin sensitivity (IS) and pancreatic ß-cell function (Pßf) in patients with prediabetes. A cross-sectional study was conducted at different times: basal, six, and twelve months in 167 Mexican adults with prediabetes. These treatments increased the abundance of GM SCFA-producing bacteria M (Fusicatenibacter and Blautia) and LM (Roseburia, Bifidobacterium, and [Eubacterium] hallii group). We performed a mediation analysis with structural equation models (SEM). In conclusion, M and LM therapies improve insulin sensitivity and Pßf in prediabetics. GM is partially associated with these improvements since the SEM models suggest a weak association between specific bacterial genera and improvements in IS and Pßf.
Assuntos
Microbioma Gastrointestinal , Linagliptina , Metformina , Estado Pré-Diabético , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Linagliptina/uso terapêutico , Linagliptina/farmacologia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina , Adulto , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , IdosoRESUMO
Recent studies have shown that maternal vitamin D deficiency (VDD) causes long-term metabolic changes in offspring. However, little is known about the impact of maternal VDD on offspring endocrine pancreas development and insulin secretion in the adult life of male and female animals. Female rats (Wistar Hannover) were fed either control (1000 IU Vitamin D3/kg), VDD (0 IU Vitamin D3/kg), or a Ca2+-enriched VDD diet (0 IU Vitamin D3/kg + Ca2+ and P/kg) for 6 weeks and during gestation and lactation. At weaning, VDD status was confirmed based on low serum calcidiol levels in dams and pups. Next, male and female offspring were randomly separated and fed a standard diet for up to 90 days. At this age, serum calcidiol levels were restored to normal levels in all groups, but serum insulin levels were decreased in VDD males without affecting glucagon levels, glycemia, or glucose tolerance. Islets isolated from VDD males showed lower insulin secretion in response to different glucose concentrations, but this effect was not observed in VDD females. Furthermore, VDD males, but not females, showed a smaller total pancreatic islet area and lower ß cell mass, an effect that was accompanied by reduced gene expression of Ins1, Ins2, Pdx1, and SLC2A2. The decrease in Pdx1 expression was not related to the methylation profile of the promoter region of this gene. Most of these effects were observed in the male VDD+Ca2+ group, indicating that the effects were not due to alterations in Ca2+ metabolism. These data show that maternal VDD selectively impairs the morphology and function of ß cells in adult male offspring rats and that female offspring are fully protected from these deleterious effects.
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Células Secretoras de Insulina , Insulina , Ratos Wistar , Deficiência de Vitamina D , Animais , Feminino , Células Secretoras de Insulina/metabolismo , Masculino , Deficiência de Vitamina D/metabolismo , Ratos , Gravidez , Insulina/sangue , Insulina/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/etiologia , Fatores Sexuais , Secreção de InsulinaRESUMO
Abstract Background: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM). Methods: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated. Results: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients. Conclusion: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.
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INTRODUCTION: This study developed a simple algorithm based on clinical results described in medical literature and which allows one to simplify complex insulin regimes with IdegLira to avoid adverse events related to the complexity of some insulin treatments. METHODS: We conducted a systematic review of the literature that allowed us to identify studies that evaluated the clinical result of simplifying complex insulin regimes. The authors reviewed the common factors these simpler regimes had, including the type of patients who used them. RESULTS: We found nine clinical studies published between 2017 and 2022, eight performed in Europe and one in Latin America. The monitoring time of the studies ranged between 3 and 18 months. The size of the study populations was between 61 and 611 patients (the latter was in five countries). In all studies, HbA1c decreased by 0.6-1.7% and the weight decreased by 0.1-3.11 kg. CONCLUSIONS: On the basis of the findings of these studies, we made some recommendations for clinical practice to simplify treatment. The results of these studies support an algorithm that simplifies the treatment of complex insulin regimens.
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Introduction: People with hazardous alcohol use are more susceptible to viral, bacterial, and fungal infections due to the effect of alcohol on immune system cell function. Metabolized ethanol reduces NAD+ to NADH, affecting critical metabolic pathways. Here, our aim was to investigate whether alcohol is metabolized by bone marrow cells and if it impacts the metabolic pathways of leukocyte progenitor cells. This is said to lead to a qualitative and quantitative alteration of key metabolites which may be related to the immune response. Methods: We addressed this aim by using C57BL/6 mice under chronic ethanol administration and evaluating the metabolomic profile of bone marrow total cells by gas chromatography-coupled mass spectrometry (GC-MS). Results: We identified 19 metabolites. Our data demonstrated that chronic ethanol administration alters the metabolomic profile in the bone marrow, resulting in a statistically diminished abundance of five metabolites in ethanol-treated animals: uracil, succinate, proline, nicotinamide, and tyrosine. Discussion: Our results demonstrate for the first time in the literature the effects of alcohol consumption on the metabolome content of hematopoietic tissue and open a wide range of further studies to investigate mechanisms by which alcohol compromises the cellular function of the immune system.
Assuntos
Medula Óssea , Etanol , Camundongos , Animais , Camundongos Endogâmicos C57BL , Etanol/farmacologia , Metabolômica/métodos , MetabolomaRESUMO
AIM: It has been suggested that the proliferation and early differentiation of myoblasts are impaired in Marfan syndrome (MFS) mice during muscle regeneration. However, the underlying cellular and molecular mechanisms remain poorly understood. Here, we investigated muscle regeneration in MFS mouse models by analyzing the influence of the fibrotic niche on satellite cell function. METHODS: In vivo, ex vivo, and in vitro experiments were performed. In addition, we evaluated the effect of the pharmacological inhibition of fibrosis using Ang-(1-7) on regenerating skeletal muscles of MFS mice. RESULTS: The skeletal muscle of MFS mice shows an increased accumulation of collagen fibers (81.2%), number of fibroblasts (157.1%), and Smad2/3 signaling (110.5%), as well as an aberrant number of fibro-adipogenic progenitor cells in response to injury compared with wild-type mice. There was an increased number of proinflammatory and anti-inflammatory macrophages (3.6- and 3.1-fold, respectively) in regenerating muscles of wild-type mice, but not in the regenerating muscles of MFS mice. Our data show that proliferation and differentiation of satellite cells are altered (p ≤ 0.05) in MFS mice. Myoblast transplantation assay revealed that the regenerating muscles from MFS mice have reduced satellite cell self-renewal capacity (74.7%). In addition, we found that treatment with Ang-(1-7) reduces fibrosis (71.6%) and ameliorates satellite cell dysfunction (p ≤ 0.05) and muscle contractile function (p ≤ 0.05) in MFS mice. CONCLUSION: The fibrotic niche, caused by Fbn1 mutations, reduces the myogenic potential of satellite cells, affecting structural and functional muscle regeneration. In addition, the fibrosis inhibitor Ang-(1-7) partially counteracts satellite cell abnormalities and restores myofiber size and contractile force in regenerating muscles.
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Síndrome de Marfan , Células Satélites de Músculo Esquelético , Camundongos , Animais , Síndrome de Marfan/patologia , Músculo Esquelético/fisiologia , Células Satélites de Músculo Esquelético/fisiologia , Diferenciação Celular , Modelos Animais de Doenças , Regeneração/fisiologia , FibroseRESUMO
Abstract This study aimed to compare the effects of diet and exercise of different intensities on antioxidant function, aortic endothelial cell function and serum lipids in NAFLD (nonalcoholic fatty liver disease) rats. Fifty Sprague-Dawley (SD) rats (180-220g) were randomly divided into two experimental groups and fed either a standard rodent chow diet (CON; n=10) or a high-fat diet (HFD; n=40). After 16 weeks, the animals that received the HFD were randomly separated into a high-fat control group (HFC; n=10) or three exercise training groups: HFD and low-intensity exercise (LE; n=10), HFD and moderate-intensity exercise (ME; n=10), and HFD and incremental intensity exercise (IE; n=10). These experimental rats keep sedentary or trained for the next six weeks. A detection kit was used to detect nitric oxide synthase (NOs), nitric oxide (NO), malondialdehyde (MDA) and other markers of aortic oxidative stress. The expression levels of endothelial nitric oxide synthase (e-NOS) and endothelin-1 (ET-1) were detected by immunohistochemistry. TC, TG, and other lipid metabolism parameters were detected by an automatic analyzer. Exercise with different intensities could improve lipid metabolism, enhance antioxidant function, reduce MDA (P<0.01), increase NO (P<0.01), and improve the expression of e-NOS and ET-1 (P<0.01) protein levels in NAFLD rats. Decreased blood lipids were exhibited in all exercise groups. Notably, the moderate-intensity exercise demonstrated more effect on increasing glutathione (GSH) contents (P<0.01) and decreased the expression of ET-1 protein levels (P<0.01). The results showed that exercise at different intensities improved lipid metabolism and enhanced anti-oxidation function. Moderate exercise could improve the function of aortic endothelial cells.
Resumen Este estudio tuvo como objetivo comparar los efectos de la dieta y el ejercicio a diferentes intensidades sobre la función antioxidante, la función de las células endoteliales aórticas y los lípidos séricos en ratas NAFLD (con enfermedad del hígado graso no alcohólico) y alimentados con una dieta estándar para roedores (CON; n = 10) o con una dieta alta en grasas (HFD; n = 40). Después de 16 semanas, los animales que recibieron HFD se separaron aleatoriamente en un grupo de control alto en grasas (HFC; n=10) o tres grupos de entrenamiento físico: HFD y ejercicio de baja intensidad (LE; n=10), HFD y ejercicio de intensidad moderada (ME; n=10), y HFD y ejercicio de intensidad incremental (IE; n=10). Estas ratas experimentales se mantuvieron sedentarias o entrenadas durante las próximas seis semanas. Se utilizó un kit de detección para determinar óxido nítrico sintetasa (NO), óxido nítrico (NO), malondialdehído (MDA) y otros marcadores de estrés oxidativo aórtico. Los niveles de expresión de la óxido nítrico sintetasa endotelial (e-NOS) y endotelina-1 (ET-1) se detectaron mediante inmunohistoquímica. El analizador automático detectó TC, TG y otros parámetros del metabolismo de los lípidos. El ejercicio con diferente intensidad mejoró el metabolismo de los lípidos, mejoró la función antioxidante, redujo la MDA (P <0,01), aumentó el NO (P <0,01) y mejoró la expresión de los niveles de proteína e-NOS y ET-1 (P <0,01) en ratas NAFLD. Se observó una disminución de los lípidos en sangre en todos los grupos de ejercicio. En particular, el ejercicio de intensidad moderada demostró un mayor efecto en el aumento del contenido de glutatión (GSH) (P<0,01) y disminuyó la expresión de los niveles de proteína ET-1 (P<0,01). Los resultados mostraron que el ejercicio a diferentes intensidades mejoró el metabolismo de los lípidos y mejoró función antioxidante. El ejercicio moderado podría mejorar la función de las células endoteliales aórticas.
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BACKGROUND: FokI (rs2228570 T>C) and BsmI (rs1544410 A>G) polymorphisms of the vitamin D receptor (VDR) have been associated to abnormal glucose metabolism and could be inversely associated with ß-cell function (BCF) and vitamin D status. There is a lack of information about this topic in the Mexican population. AIM OF THE STUDY: To evaluate the relationship between VDR gene polymorphisms FokI and BsmI with BCF and vitamin D status in a population of non-obese Mexican adults. METHODS: A sample of 192 participants were enrolled during 2016-2018. Blood samples were collected to determine fasting concentrations of glucose, insulin, and vitamin D. Genomic DNA was isolated from leucocytes and the polymorphic variants of FokI and BsmI were analyzed. The Homeostasis Model Assessment Calculator was used to estimate the BCF (HOMA2-B). RESULTS: FokI polymorphism showed a frequency of 20.1% for homozygous TT carriers and 7.8% for the BsmI GG. The recessive model of FokI (TT genotype) showed a lower mean value of BCF compared to the combination of CC + CT (99.2 vs. 109.6%, p = 0.045). Likewise, significantly lower mean values of HOMA2-B and insulin were observed for BsmI (GG genotype, p = 0.016 and p = 0.039, respectively). After covariates adjustment, only FokI polymorphism remained as an independent predictor of BCF. CONCLUSIONS: the TT and GG variants of the FokI and BsmI polymorphisms are related to a decrease in FCB. In the case of FokI, this decrement was independent of insulin sensitivity, vitamin D levels, percentage of body fat, gender, and age.
Assuntos
Insulinas , Receptores de Calcitriol/genética , Adulto , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Vitamina DRESUMO
Background: Adverse intrauterine environment-reflected by low birth weight (LBW)-has been linked to insulin resistance and type 2 diabetes later in life. Whether ß-cell function reduction and insulin resistance could be detected even in middle-aged adults without overt diabetes is less investigated. We examined the association of LBW with ß-cell function and insulin sensitivity in non-diabetic middle-aged adults from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: This is a cross-sectional analysis of 2,634 ELSA-Brasil participants aged between 34 and 59 years, without diabetes. Participants were stratified according to LBW defined as <2.5 kg and their clinical data were compared. HOMA-IR, HOMA-ß, HOMA-adiponectin, TyG index, QUICKI and TG/HDL were calculated and their association with LBW were tested using multiple linear regression including adjustments suggested by Directed Acyclic Graphs and propensity score matching was applied. Results: The sample (47.4 ± 6.3 years) was composed of 57.5% of women and 9% had LBW. Subjects with LBW and normal-weight reported similar BMI values at the age of 20 years and current BMI was slightly lower in the LBW group. In average, cardiometabolic risk profile and also indexes of ß-cell function and insulin sensitivity were within normal ranges. In regression analysis, log-transformed HOMA-ß-but not with the other indexes-was associated with LBW (p = 0.014) independent of sex, skin color, prematurity, and family history of diabetes. After applying propensity-score matching in a well-balanced sample, HOMA-AD and TG/HDL indexes were associated with LBW. Conclusion: The association between LBW and insulin sensitivity markers may occur in healthy middle-aged adults before overt glucose metabolism disturbances. Our data are coherent with the detection of early life events consequent with insulin resistance markers that could contribute to the risk of glucose metabolism disturbances.