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1.
Food Chem ; 399: 133999, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36037688

RESUMEN

Melastoma dodecandrum Lour. (MDL) extracts have shown potent α-glucosidase inhibitory activity, suggesting MDL might be a good source of α-glucosidase inhibitors. The aim of the study was to identify compounds in MDL extracts with α-glucosidase inhibitory activities and evaluate their effect on postprandial blood glucose as well as elucidating the underlying mechanisms of inhibition. A total of 34 polyphenols were identified in MDL fruits, among which 10 anthocyanins and three proanthocyanidin derivatives were discovered for the first time. Dosing mice with MDL extracts (100 mg/kg body weight, by gavage) was associated with a significantly decrease in postprandial blood glucose concentrations after oral administration of maltose. The most potent α-glucosidase inhibitor was identified as casuarictin (IC50 of 0.21 µg/mL). Casuarictin bound competitively to α-glucosidase, occupying not only the catalytic site but also forming strong hydrogen bonds with α-glucosidase residues. Therefore, casuarictin derived from MDL fruits might be used as novel α-glucosidase inhibitor in functional foods or other dietary products.


Asunto(s)
Inhibidores de Glicósido Hidrolasas , Melastomataceae , Animales , Antocianinas , Glucemia/metabolismo , Frutas/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacología , Melastomataceae/metabolismo , Ratones , Extractos Vegetales/química , alfa-Glucosidasas/metabolismo
2.
J Proteomics ; 271: 104769, 2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36372392

RESUMEN

OBJECTIVE: This study aims to find new plasma biomarkers in early pregnancy. DESIGN: The original study enrolled 1219 pregnant women. We investigated protein expression profiles of placental tissues from women with GDM (n = 89) and normal glucose tolerance (NGT) (n = 83). Maternal plasma samples between two groups in early and middle pregnancy were used for validation of candidate biomarkers. METHODS: Differentially expressed proteins (DEPs) were identified by label-free quantitative proteomics from human placenta samples between two groups. Several DEPs were validated in plasma by Luminex assays. An automatic biochemical analyzer was used to detect blood lipid indexes. The associations of GAL-3BP with biochemical indicators were demonstrated by Pearson's correlation analysis. Binary logistic regression was used to model potential predictive indicators in early pregnancy of GDM. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of the predictive model and the value of GAL-3BP. RESULTS: 123 DEPs were found in placenta involved in ribosomal function, pancreatic secretion, oxidative phosphorylation, and inflammatory signaling pathway. Plasma GAL-3BP are significantly higher in women with GDM than NGT in the first (p = 0.008) and second (p = 0.026) trimester, but C9 and VWF have no difference. The predictive value of GAL-3BP in the first trimester of pregnancy (AUC 0.64) is better than that in the second trimester (AUC 0.61), and combined predictive model of TG and GAL-3BP at early pregnancy has greater predictive and diagnostic value for GDM (AUC 0.69) than individual GAL-3BP (AUC 0.64). CONCLUSIONS: Plasma TG and GAL-3BP has good predictive and diagnostic value at early pregnancy, suggesting that these two indicators may be used as biomarkers for early prediction and diagnosis of GDM. SIGNIFICANCE: The advantage of this study is that circulating TG and GAL-3BP might differentiate the progress of women with GDM and normal glucose tolerance (NGT) at the early stage of pregnancy. It is the first study to consider the role of GAL-3BP as an early predictive biomarker in the development of GDM during the whole pregnancy. Another advantage is that volunteers in this study were recruited from two provinces in China to eliminate the impacts of environmental confounders. The similar changes of blood glucose/lipid indicators for women with GDM and NGT in both regions was found in the first and second trimester of pregnancy, which added to the reliability of analytical results.


Asunto(s)
Diabetes Gestacional , Femenino , Embarazo , Humanos , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/metabolismo , Estudios de Casos y Controles , Reproducibilidad de los Resultados , Placenta/química , Biomarcadores/metabolismo , Glucemia/metabolismo , China , Lípidos
3.
Sci Total Environ ; 857(Pt 3): 159570, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36283523

RESUMEN

Phthalate metabolites are widely present in humans and can have many adverse effects on pregnant women. To date, many studies on the effects of phthalate metabolites on the risk of gestational diabetes mellitus (GDM) have been published, but the findings of these studies are controversial. We conducted a case-control study to quantify the concentrations of seven phthalate metabolites in the serum of pregnant women and to investigate their association with the risk of GDM and blood glucose levels in pregnant women. Therefore, 201 serum samples (139 pregnant women with GDM and 62 control serum samples) were collected from Hangzhou, China, between 2011 and 2012. The results showed that mono butyl phthalate (MBP; mean = 4.08 ng/mL) was the most abundant phthalate metabolites in human serum, followed by mono (2-ethylhexyl) phthalate (MEHP; mean = 1.28 ng/mL) and mono isobutyl phthalate (MiBP; mean = 1.20 ng/mL). The other results indicated significant associations between MBP (ß = 2.24, 95 % confidence interval (CI): 1.02, 5.07, P = 0.050) and MiBP (ß = 1.84, 95 % CI: 1.03, 3.31, P = 0.041) concentrations in human serum and the incidence of GDM. Moreover, serum MBP (ß = 0.40, 95 % CI: 0.10, 0.70, P = 0.010) and MiBP levels (ß = 0.18, 95 % CI: 0.010, 0.35, P = 0.047) in humans were positively associated with 2-hour blood glucose levels. Our study provides affirmative evidence on previously inconsistent findings that MBP and MiBP exposure may increase the risk of GDM in pregnant women.


Asunto(s)
Diabetes Gestacional , Contaminantes Ambientales , Ácidos Ftálicos , Humanos , Femenino , Embarazo , Diabetes Gestacional/epidemiología , Glucemia/metabolismo , Mujeres Embarazadas , Estudios de Casos y Controles , Ácidos Ftálicos/metabolismo , Exposición a Riesgos Ambientales
4.
Neurosci Lett ; 792: 136955, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36347339

RESUMEN

GPR139 is an orphan G-protein-coupled receptor that is expressed in restricted areas of the nervous system, including the hypothalamus. In this study, we hypothesized that GPR139 could be involved in the regulation of energy balance and metabolism. In the first part of the study, we confirmed that GPR139 is expressed in the hypothalamus and particularly in proopiomelanocortin and agouti-related peptide neurons of the mediobasal hypothalamus. Using a lentivirus with a short-hairpin RNA, we inhibited the expression of GPR139 bilaterally in the mediobasal hypothalamus of mice. The intervention promoted a 40% reduction in the hypothalamic expression of GPR139, which was accompanied by an increase in body mass, a reduction in fasting blood glucose levels, and an increase in insulin levels. In the hypothalamus, inhibition of GPR139 was accompanied by a reduction in the expression of orexin. As previous studies using a pharmacological antagonist of orexin showed a beneficial impact on type 2 diabetes and glucose metabolism, we propose that the inhibition of hypothalamic GPR139 could be acting indirectly through the orexin system to control systemic glucose and insulin. In conclusion, this study advances the characterization of GPR139 in the hypothalamus, demonstrating its involvement in the regulation of body mass, blood insulin, and glycemia.


Asunto(s)
Diabetes Mellitus Tipo 2 , Insulina , Ratones , Animales , Orexinas/metabolismo , Insulina/metabolismo , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hipotálamo/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Proteínas del Tejido Nervioso/metabolismo
5.
Mol Med Rep ; 27(1)2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36367173

RESUMEN

Increasing endogenous secretion of glucagon­like peptide (GLP)­1 is considered a promising therapeutic approach for type 2 diabetes because decreased GLP­1 plasma concentrations have been observed in patients with this condition. Nesfatin­1, which is a central and peripheral anorexigenic peptide, has been reported to release GLP­1 from enteroendocrine STC­1 cells, although whether nesfatin­1 stimulates GLP­1 secretion in vivo remains to be elucidated. Previous studies have indicated that nesfatin­1 has glucose­lowering and insulinotropic effects in mice and rats; however, the in vivo mechanism remains unclear. The present study aimed to investigate whether peripheral administration of nesfatin­1 increased blood concentrations of GLP­1 and insulin in food­deprived mice. Nesfatin­1 was administered intraperitoneally to 18­h fasted mice. Plasma GLP­1 and insulin concentrations in the mice administered 2.5 µmol/kg nesfatin­1 were higher than those in saline­treated mice. Blood glucose concentrations in mice treated with 1.25 and 2.5 µmol/kg nesfatin­1 were lower than those in saline­treated mice. The mRNA expression of preproglucagon in mouse ilea after treatment with 1.25 µmol/kg nesfatin­1 was higher than that in saline­treated mice. The administration of 1.25 µmol/kg nesfatin­1 raised GLP­1 concentrations at 30 and 60 min and insulin concentrations at 30 and 60 min after injection. Furthermore, the higher level of nesfatin­1­induced insulin was diminished by pre­administration of anti­GLP­1 antiserum. Intraperitoneally administered nesfatin­1 increased insulin concentrations by accelerating GLP­1 secretion. The results are the first in vivo demonstration of promotion of GLP­1 secretion by nesfatin­1 in the mouse, suggesting the developmental potential of nesfatin­1 for GLP­1 release.


Asunto(s)
Diabetes Mellitus Tipo 2 , Péptido 1 Similar al Glucagón , Ratones , Ratas , Animales , Diabetes Mellitus Tipo 2/metabolismo , Células Enteroendocrinas , Insulina/metabolismo , Glucosa/metabolismo , Glucemia/metabolismo
6.
Physiol Rev ; 103(1): 7-30, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-35635320

RESUMEN

In this paper, we provide an overview of the evolution of the definition of hyperglycemia during the past century and the alterations in glucose dynamics that cause fasting and postprandial hyperglycemia. We discuss how extensive mechanistic, physiological research into the factors and pathways that regulate the appearance of glucose in the circulation and its uptake and metabolism by tissues and organs has contributed knowledge that has advanced our understanding of different types of hyperglycemia, namely prediabetes and diabetes and their subtypes (impaired fasting plasma glucose, impaired glucose tolerance, combined impaired fasting plasma glucose, impaired glucose tolerance, type 1 diabetes, type 2 diabetes, gestational diabetes mellitus), their relationships with medical complications, and how to prevent and treat hyperglycemia.


Asunto(s)
Diabetes Mellitus Tipo 2 , Intolerancia a la Glucosa , Hiperglucemia , Estado Prediabético , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Glucosa , Intolerancia a la Glucosa/metabolismo , Humanos , Hiperglucemia/metabolismo , Estado Prediabético/diagnóstico , Embarazo , Azúcares
7.
J Steroid Biochem Mol Biol ; 225: 106198, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36181990

RESUMEN

To evaluate the effects of long-term vitamin D supplementation on metabolic profiles in middle-aged to elderly patients with type 2 diabetes (T2D), a randomized controlled trial was conducted among patients with T2D aged 50-70 years. A total of 270 patients underwent randomization with 135 being allocated to the vitamin D group and 135 to the control group, and participants in the vitamin D group received oral vitamin D3 (800 IU/day) for 30 months. Serum 25(OH)D and metabolic variables were measured at baseline, and after 6, 12, 18, and 30 months of intervention. After 30 months, the vitamin D group showed a greater increase in serum 25(OH)D than the control group (12.39 ± 6.99 vs 5.35 ± 5.29 ng/ml, P < 0.001). Meanwhile, changes in the levels of fasting insulin, HOMA-IR, non-high-density-lipoprotein cholesterol (non-HDL-C), high-sensitivity C-reactive protein (hs-CRP), and uric acid differed significantly between the two groups (all P < 0.05). Stratified analysis indicated that change in uric acid differed significantly between the two groups in subgroup with baseline 25(OH)D ≥ 20 ng/ml (P = 0.042) or subgroup with female patients (P = 0.034). And the change in fasting blood glucose (FBG) differed significantly between the vitamin D group (-0.30 ± 2.52 mmol/L) and the control group (0.49 ± 1.78 mmol/L, P = 0.049) among patients achieving 25(OH)D concentrations of 30 ng/ml at the end of this trial. A significant difference in the change of triglyceride was observed between the two groups among patients with obesity at baseline [0.05(-0.59, 0.23) vs 0.41(-0.01, 0.80) mmol/L, P = 0.023]. These findings suggested that long-term vitamin D supplementation significantly reduced fasting insulin, HOMA-IR, and serum concentrations of non-HDL-C, hs-CRP, and uric acid among middle-aged to elderly patients with T2D. And vitamin D status, gender, and baseline obesity may modify the effects of vitamin D supplementation.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Persona de Mediana Edad , Anciano , Humanos , Femenino , Vitamina D/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Proteína C-Reactiva/metabolismo , Ácido Úrico , Glucemia/metabolismo , Suplementos Dietéticos , Vitaminas/uso terapéutico , Insulina/metabolismo , Obesidad , Metaboloma , Método Doble Ciego
8.
J Ethnopharmacol ; 301: 115791, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36240976

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang-zhenzhu-tiaozhi formula (FTZ) is a patented preparation of traditional Chinese medicine that has been used to treat hyperglycemia and hyperlipidemia in the clinic for almost 10 years. Our previous study had demonstrated that FTZ can protect islet ß cell injury in vitro. However, the efficacy of FTZ on ß cell regeneration in vivo and the involved anti-diabetic mechanism remains unknown. AIM OF THE STUDY: We aim to investigate the effects of FTZ as a good remedy for islet protection and ß cell regeneration, and to reveal the underlying mechanism. MATERIALS AND METHODS: C57BL/6 mice were fed with high-fat diet for 3 weeks and then intraperitoneally injected with streptozotocin (90 mg/kg/d × 1 d) to establish type 2 diabetes (T2D) models. Mice in each group were divided into three batches that sacrificed after 3, 7 and 28 days of FTZ administration. Body weight, blood glucose, and oral glucose tolerance test were measured at indicated time points. Fasting insulin was determined by enzyme-linked immunosorbent assay (ELISA) kit. Neonatal ß cell was assessed by insulin & PCNA double immunofluorescence staining, and the underlying mechanisms related to ß cell regeneration were further performed by hematoxylin-eosin staining, insulin & glucagon double immunofluorescence staining and Western blot. RESULTS: FTZ and metformin can significantly help with the symptoms of DM, such as alleviating weight loss, reducing blood glucose, improving the level of insulin in vivo, and relieving insulin resistance, suggesting FTZ and metformin treatment maintained the normal morphological function of islet. Notably, ß cell regeneration, which is indicated by insulin and PCNA double-positive cells, was promoted by FTZ, whereas few neonatal ß cells were observed in metformin group. Hematoxylin-eosin staining, and its quantification results showed that FTZ effectively prevented the invasion of inflammatory cells into the islets in diabetic mice. Most ß cells in the islets of diabetic model mice were devoid, and the islets were almost all α cells, while the diabetic mice administered FTZ could still maintain about half of the ß cells in the islet. Furthermore, FTZ upregulated the expression of critical transcription factors during ß cell development and maturation (such as PDX-1, MAFA and NGN3) in diabetic mice. CONCLUSIONS: FTZ can alleviate diabetes symptoms and promote ß cell regeneration in diabetic mice. Moreover, FTZ promotes ß cell regeneration by preserving islet (resisting inflammatory cells invading islets), maintaining the number of ß cells in islets, and increasing the expression of PDX-1, MAFA and NGN3.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Islotes Pancreáticos , Metformina , Ratones , Animales , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Eosina Amarillenta-(YS)/metabolismo , Eosina Amarillenta-(YS)/farmacología , Hematoxilina/metabolismo , Hematoxilina/farmacología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ratones Endogámicos C57BL , Insulina , Regeneración , Metformina/farmacología
9.
Horm Metab Res ; 54(2): 104-112, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35130571

RESUMEN

Some studies have suggested that diabetes may be a risk factor for osteoarthritis. However, whether prediabetes is also associated with osteoarthritis has not been comprehensively examined. We performed a meta-analysis to evaluate the relationship between prediabetes and osteoarthritis. This meta-analysis included relevant observational studies from Medline, Embase, and Web of Science databases. A random-effect model after incorporation of the intra-study heterogeneity was selected to pool the results. Ten datasets from six observational studies were included, which involved 41 226 general adults and 10 785 (26.2%) of them were prediabetic. Pooled results showed that prediabetes was not independently associated with osteoarthritis [risk ratio (RR): 1.07, 95% confidence interval (CI): 1.00 to 1.14, p=0.06, I2=0%]. Sensitivity limited to studies with adjustment of age and body mass index showed consistent result (RR: 1.06, 95% CI: 0.99 to 1.14, p=0.09, I2=0%). Results of subgroup analyses showed that prediabetes was not associated with osteoarthritis in cross-sectional or cohort studies, in studies including Asian or non-Asian population, or in studies with different quality scores (p for subgroup difference>0.10). Besides, prediabetes was not associated with osteoarthritis in men or in women, in studies with prediabetes defined as impaired fasting glucose, impaired glucose tolerance, or HbA1c (approximately 39-46 mmol/mol). Moreover, prediabetes was not associated with overall osteoarthritis, and knee or hip osteoarthritis. Current evidence does not support that prediabetes is independently associated with osteoarthritis in adult population.


Asunto(s)
Intolerancia a la Glucosa , Osteoartritis , Estado Prediabético , Adulto , Glucemia/metabolismo , Estudios Transversales , Femenino , Hemoglobina A Glucada/análisis , Humanos , Masculino , Estudios Observacionales como Asunto , Osteoartritis/complicaciones , Osteoartritis/epidemiología , Estado Prediabético/complicaciones , Estado Prediabético/epidemiología , Estado Prediabético/metabolismo , Factores de Riesgo
10.
Cell Rep ; 41(8): 111698, 2022 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-36417883

RESUMEN

Therapies based on glucagon-like peptide-1 (GLP-1) long-acting analogs and insulin are often used in the treatment of metabolic diseases. Both insulin and GLP-1 receptors are expressed in metabolically relevant brain regions, suggesting a cooperative action. However, the mechanisms underlying the synergistic actions of insulin and GLP-1R agonists remain elusive. In this study, we show that insulin-induced hypoglycemia enhances GLP-1R agonists entry in hypothalamic and area, leading to enhanced whole-body fat oxidation. Mechanistically, this phenomenon relies on the release of tanycyctic vascular endothelial growth factor A, which is selectively impaired after calorie-rich diet exposure. In humans, low blood glucose also correlates with enhanced blood-to-brain passage of insulin, suggesting that blood glucose gates the passage other energy-related signals in the brain. This study implies that the preventing hyperglycemia is important to harnessing the full benefit of GLP-1R agonist entry in the brain and action onto lipid mobilization and body weight loss.


Asunto(s)
Glucemia , Factor A de Crecimiento Endotelial Vascular , Humanos , Glucemia/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Insulina/metabolismo , Homeostasis , Encéfalo/metabolismo
11.
Nutrients ; 14(22)2022 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-36432465

RESUMEN

Time-restricted feeding (TRF) and Ramadan fasting (RF) have been recently associated with several health outcomes. However, it is not yet clear if they are superior to existing treatments in terms of glucose metabolism, insulin action, and weight loss. This review aims to summarize the current data on the effects of these regimes on body weight, body composition, and glycemia. An electronic search was conducted in PUBMED and SCOPUS databases up to August 2022. Twenty-four records met the inclusion criteria and underwent a risk-of-bias assessment. The main outcomes were: (a) TRF may result in moderate weight loss in individuals with overweight/obesity; when TRF is combined with caloric restriction, weight loss is >5% of the initial body weight, (b) 14 h of fasting may be as effective as 16 h in terms of weight loss, and (c) TRF may lead to improved insulin sensitivity and glycemic responses/variability throughout the day in individuals with overweight/obesity. Concerning RF, only two studies were available and thus, conclusions were not drawn. TRF may be an effective nutritional approach for weight loss, and the amelioration of glycemic control and insulin sensitivity in individuals with overweight/obesity. However, more long-term, well-designed studies are needed.


Asunto(s)
Ayuno , Resistencia a la Insulina , Humanos , Glucemia/metabolismo , Composición Corporal/fisiología , Peso Corporal , Ayuno/fisiología , Glucosa , Resistencia a la Insulina/fisiología , Obesidad/complicaciones , Sobrepeso/complicaciones , Ensayos Clínicos Controlados Aleatorios como Asunto , Pérdida de Peso
12.
Diabetes Care ; 45(12): 2982-2990, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36326757

RESUMEN

OBJECTIVE: We studied longitudinal differences between progressors and nonprogressors to type 1 diabetes with similar and substantial baseline risk. RESEARCH DESIGN AND METHODS: Changes in 2-h oral glucose tolerance test indices were used to examine variability in diabetes progression in the Diabetes Prevention Trial-Type 1 (DPT-1) study (n = 246) and Type 1 Diabetes TrialNet Pathway to Prevention study (TNPTP) (n = 503) among autoantibody (Ab)+ children (aged <18.0 years) with similar baseline metabolic impairment (DPT-1 Risk Score [DPTRS] of 6.5-7.5), as well as in TNPTP Ab- children (n = 94). RESULTS: Longitudinal analyses revealed annualized area under the curve (AUC) of C-peptide increases in nonprogressors versus decreases in progressors (P ≤ 0.026 for DPT-1 and TNPTP). Vector indices for AUC glucose and AUC C-peptide changes (on a two-dimensional grid) also differed significantly (P < 0.001). Despite marked baseline metabolic impairment of nonprogressors, changes in AUC C-peptide, AUC glucose, AUC C-peptide-to-AUC glucose ratio (AUC ratio), and Index60 did not differ from Ab- relatives during follow-up. Divergence between nonprogressors and progressors occurred by 6 months from baseline in both cohorts (AUC glucose, P ≤ 0.007; AUC ratio, P ≤ 0.034; Index60, P < 0.001; vector indices of change, P < 0.001). Differences in 6-month change were positively associated with greater diabetes risk (respectively, P < 0.001, P ≤ 0.019, P < 0.001, and P < 0.001) in DPT-1 and TNPTP, except AUC ratio, which was inversely associated with risk (P < 0.001). CONCLUSIONS: Novel findings show that even with similarly abnormal baseline risk, progressors had appreciably more metabolic impairment than nonprogressors within 6 months and that the measures showing impairment were predictive of type 1 diabetes. Longitudinal metabolic patterns did not differ between nonprogressors and Ab- relatives, suggesting persistent ß-cell responsiveness in nonprogressors.


Asunto(s)
Diabetes Mellitus Tipo 1 , Niño , Humanos , Péptido C/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico , Glucemia/metabolismo , Prueba de Tolerancia a la Glucosa , Autoanticuerpos , Glucosa , Progresión de la Enfermedad
13.
Cells ; 11(21)2022 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-36359767

RESUMEN

Sodium-glucose cotransporter-2 inhibitors (SGLT2is), such as empagliflozin, lower blood glucose in type 2 diabetes mellitus and improve cardiorenal outcomes regardless of diabetes presence. Whether SGLT2is exert any effects on the brain's metabolism has not been studied. We conducted a single-arm clinical trial to investigate the effects of once daily administration of oral empagliflozin (25 mg) for 14 days on systemic and brain metabolism in 21 non-diabetics aged 55 years old or older. Empagliflozin lowered circulating insulin and elevated ß-hydroxybutyrate over 34-h periods, both following its first administration and after 14 days of daily administration, with minor alterations in glucose homeostasis. Levels of phosphorylated insulin-like growth factor-1 receptor (pIGF-1R), phosphorylated insulin receptor (pIR), phosphorylated-in-tyrosine insulin receptor substrate-1 (pY-IRS-1), and phosphorylated protein kinase B or AKT (pAKT) were increased in extracellular vesicles enriched for neuronal origin (NEVs) following the first empagliflozin administration, but not after 14 days. Our finding of IGF-1R upregulation in NEVs is promising because several post-mortem and epidemiological studies support the idea that upregulation of IGF signaling may protect against Alzheimer's disease (AD). Moreover, our finding showing activation of insulin signaling and, in particular, the canonical pathway (pIR, pY-IRS-1, pAKT) in NEVs is important because such changes have been repeatedly associated with neuronal survival. Using brain magnetic resonance spectroscopy (MRS), we detected decreased concentrations of the excitatory neurotransmitter glutamate and its precursor glutamine after empagliflozin administration. This finding is also encouraging since glutamatergic excitotoxicity has long been implicated in AD pathology. Overall, our findings may motivate the repurposing of SGLT2is for use in AD and other, related diseases that are characterized by downregulation of IGF-1/insulin signaling in neurons and excitotoxicity.


Asunto(s)
Enfermedad de Alzheimer , Diabetes Mellitus Tipo 2 , Cetosis , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Femenino , Humanos , Persona de Mediana Edad , Enfermedad de Alzheimer/metabolismo , Glucemia/metabolismo , Encéfalo/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Ácido Glutámico/metabolismo , Insulina/metabolismo , Insulina Regular Humana/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Cetosis/metabolismo , Neuronas/metabolismo , Neurotransmisores/metabolismo , Factor de Crecimiento Placentario/metabolismo , Factor de Crecimiento Placentario/farmacología , Receptor de Insulina/metabolismo , Transducción de Señal , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología
14.
ACS Nano ; 16(11): 18223-18231, 2022 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-36322923

RESUMEN

Glucose-responsive insulin delivery systems that mimic insulin secretion activity in the pancreas show great potential to improve clinical therapeutic outcomes for people with type 1 and advanced type 2 diabetes. Here, we report a glucose-responsive insulin delivery microneedle (MN) array patch that is loaded with red blood cell (RBC) vesicles or liposome nanoparticles containing glucose transporters (GLUTs) bound with glucosamine-modified insulin (Glu-Insulin). In hyperglycemic conditions, high concentrations of glucose in interstitial fluid can replace Glu-Insulin via a competitive interaction with GLUT, leading to a quick release of Glu-Insulin and subsequent regulation of blood glucose (BG) levels in vivo. To prolong the effective glucose-responsive insulin release from MNs, additional free Glu-Insulin, which serves as "stored insulin", is loaded after RBC vesicles or liposome nanoparticles bound with Glu-Insulin. In the streptozotocin (STZ)-induced type 1 diabetic mouse model, this smart GLUT-based insulin patch can effectively control BG levels without causing hypoglycemia.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Ratones , Animales , Insulina/metabolismo , Proteínas Facilitadoras del Transporte de la Glucosa/uso terapéutico , Liposomas/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Experimental/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Glucosa/metabolismo , Glucemia/metabolismo , Agujas
15.
Artículo en Inglés | MEDLINE | ID: mdl-36430066

RESUMEN

The ideal lifestyle intervention to battle both obesity and diabetes is currently unknown. The aim of this pilot uncontrolled intervention trial was to assess the effect of a modified Mediterranean diet (MedDiet) on weight loss and glucoregulation among overweight/obese adults. Eleven men and women with overweight/obesity, aged 37 ± 12 years, participated in a free-living intervention until 10% weight loss was achieved. Participants followed an individualized MedDiet high in monounsaturated fat and protein with decreased carbohydrate and saturated fat contents. Physical activity and dietary intake were monitored with pedometers and food records, respectively. Upon weight loss achievement, anthropometric measurements, blood metabolic profiles and individual responses to oral glucose and mixed-meal tests were evaluated pre- and post-intervention. The results showed significant ameliorations in body fat, waist circumference and leptin levels (p < 0.01), with concomitant increases in adiponectin-leptin ratios (p < 0.001). Glucoregulation was significantly improved according to glucose and insulin responses, homeostatic model assessment of insulin resistance indices and postprandial insulin sensitivity indices (p < 0.05). In conclusion, the modified Mediterranean diet may induce significant improvements in body composition, adipocytokine profile and glucose metabolism in overweight/obese individuals. Notably, ameliorated glycemia and increased insulin sensitivity may be retained even at postprandial level, irrespective of the meal consumed.


Asunto(s)
Dieta Mediterránea , Resistencia a la Insulina , Masculino , Adulto , Femenino , Humanos , Sobrepeso/complicaciones , Ayuno , Leptina , Proyectos Piloto , Obesidad/complicaciones , Pérdida de Peso/fisiología , Glucemia/metabolismo , Insulina
16.
Lipids Health Dis ; 21(1): 126, 2022 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-36435770

RESUMEN

BACKGROUND: Due to the contribution of coronary artery disease (CAD) to serious cardiovascular events, determining biomarkers that could robustly predict its risk would be of utmost importance. Thus, this research was designed to assess the value of traditional cardio-metabolic indices, and more novel atherogenicity indices and insulin resistance surrogate markers in the identification of individuals at risk of CAD. METHODS: A case‒control survey was conducted, in which 3085 individuals were enrolled. Their clinical and biochemical data were gathered at baseline. The investigated indices included the atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), lipoprotein combine index (LCI), cholesterol index (CHOLINDEX), Castelli's risk indices-I, II (CRI-I, CRI-II), and metabolic score for insulin resistance (METS - IR). To examine the relationship between these variables and CAD risk, multiple regression analyses adjusted for potential confounders were conducted. RESULTS: Overall, 774 angiographically confirmed CAD patients (mean age = 54 years) were compared with 3085 controls (mean age = 51 years). Higher triglyceride, total cholesterol and fasting blood sugar levels and lower HDL-C levels were related to an elevated risk of CAD (P-for-trend < 0.001), while the direct association between increased serum LDL-C concentrations and a greater risk of CAD only became apparent when excluding those with diabetes, and statin users. Among novel indices, greater values of the majority of these markers, including AIP, CRI-I, and -II, CHOLINDEX, LCI, and TyG-index, in comparison to the lower values, significantly elevated CAD risk (P-for-trend < 0.001). CONCLUSION: According to the current findings, novel atherogenicity indices and insulin resistance surrogate markers, in particular, AIP, CRI-I and II, CHOLINDEX, LCI, and TyG-index, may be useful in predicting CAD risk.


Asunto(s)
Enfermedad de la Arteria Coronaria , Resistencia a la Insulina , Humanos , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/diagnóstico , Glucemia/metabolismo , Biomarcadores , Triglicéridos , Estudios de Casos y Controles , Glucosa/metabolismo , Factores de Riesgo
17.
Endocrinol Diabetes Nutr (Engl Ed) ; 69(8): 576-583, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36347795

RESUMEN

INTRODUCTION: Development of cystic fibrosis-related diabetes (CFRD) is associated with worsening of nutritional status and lung function, as well as increased mortality. The relevance of diagnosing the «pre-diabetic¼ status in these patients has not been addressed and the utility of HbA1c measurement in these patients is under discussion. AIM: To study and characterise the different categories of carbohydrate metabolism impairment in paediatric patients with cystic fibrosis. PATIENTS AND METHODS: A transversal study for characterisation of carbohydrate metabolism impairment according to clinical and anthropometric status and genetic background in 50 paediatric patients with cystic fibrosis (CF) was undertaken. Oral glucose tolerance tests (OGTT) for determination of glucose and insulin levels measurement and continuous subcutaneous glucose monitoring (CSGM) were performed. RESULTS: 6% of patients presented with CFRD, 26% impaired glucose tolerance, 10% an indeterminate glucose alteration and 2% impaired fasting glucose. The severity of glycaemic impairment correlated positively with age and negatively with standardised height (p < 0.05) with intergroup differences in HbA1c levels (p < 0.01), with the latter correlating with the duration of hyperglycaemia throughout CSGM. No intergroup differences in mutation prevalence, pulmonary function test, nutritional status or disease exacerbations in the previous year were found. The daily enzyme replacement dose correlated with the glucose area under the curve (AUC, p < 0.05) but not with insulin-AUC. CONCLUSIONS: An older age and greater enzyme replacement need are correlated with more severe carbohydrate metabolism impairment and lower standardized height in paediatric CF patients, with HbA1c correlating with the duration of hyperglycaemia. The study of the full glucose/insulin AUCs throughout the OGTT affords no additional information compared to glucose determination at 120 min in these patients.


Asunto(s)
Fibrosis Quística , Diabetes Mellitus , Intolerancia a la Glucosa , Estado Prediabético , Humanos , Adolescente , Niño , Fibrosis Quística/complicaciones , Glucemia/metabolismo , Automonitorización de la Glucosa Sanguínea , Hemoglobina A Glucada , Intolerancia a la Glucosa/diagnóstico , Insulina , Diabetes Mellitus/diagnóstico , Metabolismo de los Hidratos de Carbono
18.
Transpl Immunol ; 75: 101740, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36372144

RESUMEN

OBJECTIVE: This systematic literature review aims to compare the efficacy and safety of traditional and stem cell (SC) therapies for type 1 (T1DM) and type 2 (T2DM) diabetes mellitus patients. METHODS: The PubMed, SciELO, BVS, and Medline databases were searched, and 38 original articles were selected, which included 647 control cases and 654 treatments with three-, six- and twelve-month follow-ups of T1DM and T2DM patients. The efficacy of stem cell therapy was validated by comparing laboratory parameters such as fasting blood glucose and C-peptide levels before and after treatment. The REML model was chosen for random effects, and the inverse of variance was used for fixed effects. The statistical analysis was carried out using Bioestat 5.0 and STATA 16.0 software. RESULTS: All SC treatments significantly reduced the need for insulin following six and twelve months of treatment, whereas there was no significant decrease after three months. Fasting blood glucose and glycosylated hemoglobin levels were significantly reduced in all follow-ups with SC. In addition, SC treatment caused a significant increase in C-peptide levels. Bone marrow hematopoietic stem cell therapy produced better results than the conventional drug treatment for diabetes mellitus (semagglutide). CONCLUSION: The results with SC were significantly better, regardless of the follow-up period. Studies have proven cell therapy to be beneficial, safe, and effective.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Glucemia/análisis , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/terapia , Péptido C , Diabetes Mellitus Tipo 2/terapia , Tratamiento Basado en Trasplante de Células y Tejidos , Resultado del Tratamiento
19.
Front Endocrinol (Lausanne) ; 13: 1011238, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36325440

RESUMEN

Mutations in KCNH6 has been proved to cause hypoinsulinemia and diabetes in human and mice. Cisapride is a stomach-intestinal motility drug used to treat gastrointestinal dysfunction. Cisapride has been reported to be a potential inhibitor of the KCNH family, but it remained unclear whether cisapride inhibited KCNH6. Here, we discovered the role of cisapride on glucose metabolism, focusing on the KCNH6 potassium channel protein. Cisapride reduced blood glucose level and increased serum insulin secretion in wild-type (WT) mice fed standard normal chow/a high-fat diet or in db/db mice, especially when combined with tolbutamide. This effect was much stronger after 4 weeks of intraperitoneal injection. Whole-cell patch-clamp showed that cisapride inhibited KCNH6 currents in transfected HEK293 cells in a concentration-dependent manner. Cisapride induced an increased insulin secretion through the disruption of intracellular calcium homeostasis in a rat pancreatic ß-cell line, INS-1E. Further experiments revealed that cisapride did not decrease blood glucose or increase serum insulin in KCNH6 ß-cell knockout (Kcnh6-ß-KO) mice when compared with WT mice. Cisapride also ameliorated glucose-stimulated insulin secretion (GSIS) in response to high glucose in WT but not Kcnh6-ß-KO mice. Thus, our data reveal a novel way for the effect of KCNH6 in cisapride-induced hypoglycemia.


Asunto(s)
Glucemia , Hipoglucemia , Humanos , Ratas , Ratones , Animales , Glucemia/metabolismo , Cisaprida , Insulina/metabolismo , Canales de Potasio , Células HEK293 , Glucosa/metabolismo , Canales de Potasio Éter-A-Go-Go/genética , Canales de Potasio Éter-A-Go-Go/metabolismo
20.
Medicine (Baltimore) ; 101(45): e31342, 2022 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-36397365

RESUMEN

The Chinese Medical Doctor Association has initiated metabolic management center (MMC) program for 6 years since 2016 nationwide. It is worth investigating the level of control metabolic outcomes in patients with type2 diabetes (T2DM) after MMC model in Yan'an, northwest China. Patients with T2DM was admitted to MMC in Yan'an University Affiliated Hospital from November 2018 to July 2021. They were asked to revisit hospital every 3 months. Blood glucose, blood pressure and blood lipids at baseline were compared to its counterparts after 1 year MMC management. Glycosylated hemoglobin and low density lipoprotein cholesterol (LDL-C) level in T2DM patients after 1 year management were lower than their baseline level (glycosylated hemoglobin 7.74 ±â€…1.94% vs 8.63 ±â€…2.26%, P < .001; LDL-C 1.81 ±â€…0.73mmol/L vs 2.18 ±â€…1.49mmol/L, P < .001). Mean HOMA-ß increased after management (65.89 ±â€…90.81% vs 128.38 ±â€…293.93%, P < .05). After 1 year of management, patients in high school or above group achieved higher control rate of body mass index than those in middle school or below group (71.82% vs 28.18%, P = .043). high density lipoprotein cholesterol control rate was higher in high income group (42.86% vs 34.97%, 16.28%, P = .012), while LDL-C control rate was higher in low-income group (97.67% vs 78.57%, 84.51%, P = .018). fasting plasma glucose control rate in new diagnosis group was higher than that of the middle and long course groups (71.43% vs 52.38%, 42.44%, P = .002). The comprehensive control rate increased from 9.83% at baseline to 26.15% after 1 year MMC management. The metabolic outcomes and their control rate in T2DM patients were improved after 1 year MMC management. It indicated that patients may achieve more benefits with MMC management.


Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/metabolismo , Hemoglobina A Glucada/metabolismo , LDL-Colesterol , Glucemia/metabolismo , Índice de Masa Corporal
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