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1.
Nutrients ; 14(2)2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-35057569

RESUMEN

The reactions of intestinal functional parameters to type 2 diabetes at a young age remain unclear. The study aimed to assess changes in the activity of intestinal enzymes, glucose absorption, transporter content (SGLT1, GLUT2) and intestinal structure in young Wistar rats with type 2 diabetes (T2D) and impaired glucose tolerance (IGT). To induce these conditions in the T2D (n = 4) and IGT (n = 6) rats, we used a high-fat diet and a low dose of streptozotocin. Rats fed a high-fat diet (HFD) (n = 6) or a standard diet (SCD) (n = 6) were used as controls. The results showed that in T2D rats, the ability of the small intestine to absorb glucose was higher in comparison to HFD rats (p < 0.05). This was accompanied by a tendency towards an increase in the number of enterocytes on the villi of the small intestine in the absence of changes in the content of SGLT1 and GLUT2 in the brush border membrane of the enterocytes. T2D rats also showed lower maltase and alkaline phosphatase (AP) activity in the jejunal mucosa compared to the IGT rats (p < 0.05) and lower AP activity in the colon contents compared to the HFD (p < 0.05) and IGT (p < 0.05) rats. Thus, this study provides insights into the adaptation of the functional and structural parameters of the small intestine in the development of type 2 diabetes and impaired glucose tolerance in young representatives.


Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Intolerancia a la Glucosa/complicaciones , Glucosa/farmacocinética , Intestino Delgado/enzimología , Intestino Delgado/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Enterocitos/química , Glucano 1,4-alfa-Glucosidasa/metabolismo , Transportador de Glucosa de Tipo 2/análisis , Absorción Intestinal , Masculino , Ratas , Ratas Wistar , Transportador 1 de Sodio-Glucosa/análisis , alfa-Glucosidasas/metabolismo
2.
Br J Radiol ; 95(1130): 20200810, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34705528

RESUMEN

Metformin is widely used to treat diabetes, but induces changes in glucose uptake in both normal organs and tumors. Here, we review the effects of metformin on the uptake of 18F-fludeoxyglucose (18F-FDG) in tissues and tumors, and its influence on 18F-FDG positron emission tomographic imaging (18F-FDG PET), as well as the mechanisms involved. This is an important issue, because metformin has diverse effects on tissue uptake of 18F-FDG, and this can affect the quality and interpretation of PET images. Metformin increases glucose uptake in the gastrointestinal tract, cerebral white matter, and the kidney, while regions of the cerebrum associated with memory show decreased glucose uptake, and the myocardium shows no change. Hepatocellular carcinoma and breast cancer show increased glucose uptake after metformin administration, while thyroid cancer shows decreased uptake, and colon and pancreatic cancers show no change. A high-energy diet increases 18F-FDG uptake, but this effect is blocked by metformin. Withdrawal of metformin 48 h before PET image acquisition is widely recommended. However, based on our review of the literature, we propose that the differentiation of metformin discontinuation could be reasonable. But future clinical trials are still needed to support our viewpoint.


Asunto(s)
Fluorodesoxiglucosa F18/farmacocinética , Hipoglucemiantes/farmacología , Metformina/farmacología , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Animales , Neoplasias de la Mama/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias del Colon/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Ingestión de Energía , Femenino , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/metabolismo , Glucosa/farmacocinética , Humanos , Hiperglucemia/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Neoplasias Hepáticas/metabolismo , Ratones , Miocardio/metabolismo , Neoplasias Pancreáticas/metabolismo , Ratas , Neoplasias de la Tiroides/metabolismo , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/metabolismo
3.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 212-218, 2021 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-34817346

RESUMEN

iabetes mellitus is one of the most common non-contagious diseases. In 2017, The International Diabetes Federation reported that around 425 million people suffer from diabetes worldwide. Medications used for the treatment of diabetes lead to unwanted side effects, and thus, new safe drugs are necessary. Some natural plant-based products exhibit anti hyperglycemic activity and low toxicity. The aim of this study was to evaluate the antihyperglycemic activity (using both in vitro and in vivo models) as well as cytotoxicity of the extracts obtained from various plants. Nine extracts from a total of eight plant species were subjected to in vitro α-amylase and α-glucosidase inhibition assays. Subsequently, they were assessed through the ex vivo everted sac assay, and finally, the in vivo antihyperglycemic activity was evaluated. The extracts obtained from Ceanothus coeruleus, Chrysactinia mexicana and Zanthoxylum fagara inhibited the activities of α-amylase and α-glucosidase in the in vitro assays. Ethyl acetate and hydroalcoholic extracts from Jatropha dioica, hydroalcoholic extract from Salvia ballotaeflora and Chrysactinia mexicana, as well as methanolic extract from Ricinus communis and Zanthoxylum fagara significantly reduced the glucose uptake in the ex vivo everted intestinal sac test. All the eight extracts showed antihyperglycemic effect through the in vivo model of the Glucose Tolerance Test, using starch as the carbohydrate source.  The antihyperglycemic effect of the extracts could be mediated through the inhibition of digestive enzymes and/or the absorption of glucose through the intestine. However, the mechanism of action for the hydroalcoholic extract of Salvia texana and the methanolic extract of Turnera diffusa, which showed a strong in vivo antihyperglycemic effect, is unclear.


Asunto(s)
Diabetes Mellitus/prevención & control , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Animales , Glucemia/metabolismo , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Diabetes Mellitus/sangre , Diabetes Mellitus/metabolismo , Evaluación Preclínica de Medicamentos , Glucosa/metabolismo , Glucosa/farmacocinética , Prueba de Tolerancia a la Glucosa/métodos , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Humanos , Hipoglucemiantes/química , Absorción Intestinal/efectos de los fármacos , Masculino , Metanol/química , México , Fitoterapia/métodos , Extractos Vegetales/química , Plantas Medicinales/clasificación , Ratas Wistar , Células Vero
4.
Front Endocrinol (Lausanne) ; 12: 732338, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34707569

RESUMEN

Women with polycystic ovary syndrome (PCOS), commonly have profound skeletal muscle insulin resistance which can worsen other clinical features. The heterogeneity of the condition has made it challenging to identify the precise mechanisms that cause this insulin resistance. A possible explanation for the underlying insulin resistance may be the dysregulation of Transforming Growth Factor-beta (TGFß) signalling. TGFß signalling contributes to the remodelling of reproductive and hepatic tissues in women with PCOS. Given the systemic nature of TGFß signalling and its role in skeletal muscle homeostasis, it may be possible that these adverse effects extend to other peripheral tissues. We aimed to determine if TGFß1 could negatively regulate glucose uptake and insulin signalling in skeletal muscle of women with PCOS. We show that both myotubes from women with PCOS and healthy women displayed an increase in glucose uptake, independent of changes in insulin signalling, following short term (16 hr) TGFß1 treatment. This increase occurred despite pro-fibrotic signalling increasing via SMAD3 and connective tissue growth factor in both groups following treatment with TGFß1. Collectively, our findings show that short-term treatment with TGFß1 does not appear to influence insulin signalling or promote insulin resistance in myotubes. These findings suggest that aberrant TGFß signalling is unlikely to directly contribute to skeletal muscle insulin resistance in women with PCOS in the short term but does not rule out indirect or longer-term effects.


Asunto(s)
Glucosa/farmacocinética , Insulina/metabolismo , Fibras Musculares Esqueléticas/efectos de los fármacos , Síndrome del Ovario Poliquístico/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Adolescente , Adulto , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Estudios de Casos y Controles , Células Cultivadas , Femenino , Glucosa/metabolismo , Técnica de Clampeo de la Glucosa , Humanos , Resistencia a la Insulina/fisiología , Persona de Mediana Edad , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Síndrome del Ovario Poliquístico/patología , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/fisiología , Adulto Joven
5.
Anal Biochem ; 631: 114357, 2021 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-34469746

RESUMEN

The growth and proliferation of most cancer cells involve the excessive uptake of glucose mediated by glucose transporters. An effective strategy for cancer therapy has been to inhibit the GLUTs that are usually overexpressed in a variety of tumor cells. 2-NBDG is a GLUT1 substrate that can be used as a probe for GLUT1 inhibitors. An accurate and simple assay for 2-NBDG in a HEK293T cell model overexpressing GLUT1 was developed using liquid chromatography-tandem mass spectrometry. Chromatographic separation was achieved using a Xbridge® Amide column (3.5 µm, 2.1 mm × 150 mm, Waters) with acetonitrile-water containing 2 µM ammonium acetate (80:20, v/v) at a flow rate of 0.25 mL/min. Mass detection was conducted in the parallel reaction monitoring (PRM) mode. The calibration curve for 2-NBDG showed good linearity in the concentration range of 5-500 ng/mL with satisfactory precision, a relative standard deviation ranging from 2.92 to 9.59% and accuracy with a relative error ranging from -13.14 to 7.34%. This method was successfully applied to quantify the uptake of GLUT1-mediated 2-NBDG, and the results clearly indicated inhibition of GLUT1 by WZB117 and quercetin (two potent glucose transporter inhibitors) in the GLUT1-HEK293T cell model. This study provides a convenient and accurate method for high-throughput screening of selective and promising GLUT1 inhibitors.


Asunto(s)
4-Cloro-7-nitrobenzofurazano/análogos & derivados , Cromatografía Liquida/métodos , Desoxiglucosa/análogos & derivados , Transportador de Glucosa de Tipo 1/metabolismo , Espectrometría de Masas en Tándem/métodos , 4-Cloro-7-nitrobenzofurazano/análisis , Desoxiglucosa/análisis , Estabilidad de Medicamentos , Glucosa/farmacocinética , Transportador de Glucosa de Tipo 1/genética , Células HEK293 , Ensayos Analíticos de Alto Rendimiento/métodos , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
6.
Biomed Res Int ; 2021: 9979419, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34258287

RESUMEN

Nigella sativa (NS) is a well-known plant for its various benefits and multiuse in traditional medicine. This study is aimed at investigating the chemical composition of the different NS fractions by using GC-MS for the esterified fatty acids or HPLC-UV for organic fraction and at evaluating the inhibitory effect on pancreatic α-amylase (in vitro, in vivo) and intestinal glucose absorption. Among all the investigated fractions, it was shown that they are rich with different molecules of great interest. The n-hexane fraction was characterized by the presence of linoleic acid (44.65%), palmitic acid (16.32%), stearic acid (14.60%), and thymoquinone (8.7%), while among the identified peaks in EtOH fraction we found catechin (89.03 mg/100 g DW), rutin (6.46 mg/100 g DW), and kaempferol (0.032 mg/100 g DW). The MeOH fraction was distinguished with the presence of gallic acid (19.91 mg/100 g DW), catechin (13.79 mg/100 g DW), and rutin (21.07 mg/100 g DW). Finally, the aqueous fraction was marked by the existence of different molecules; among them, we mention salicylic acid (32.26 mg/100 g DW), rutin (21.46 mg/100 g DW), and vanillic acid (3.81 mg/100 g DW). Concerning the inhibitory effect on pancreatic α-amylase, it was found that in the in vitro study, the best IC50 registered were those of EtOH (0.25 mg/ml), MeOH (0.10 mg/ml), aqueous (0.031 mg/ml), and n-hexane fraction (0.76 mg/ml), while in the in vivo study an important inhibition of α-amylase in normal and diabetic rats was observed. Finally, the percentage of intestinal glucose absorption was evaluated for all tested extracts and it was ranging from 24.82 to 60.12%. The results of the present study showed that the NS seed fractions exert an interesting inhibitory effect of α-amylase and intestinal glucose absorption activity which could be associated with the existent bioactive compounds. Indeed, these compounds can be used as antidiabetic agents because of their nontoxic effect and high efficacy.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Glucosa/farmacocinética , Intestinos/patología , Nigella sativa/metabolismo , Páncreas/enzimología , alfa-Amilasas Pancreáticas/biosíntesis , Animales , Benzoquinonas/química , Diabetes Mellitus Experimental , Femenino , Glucosa/metabolismo , Hipoglucemiantes/farmacología , Concentración 50 Inhibidora , Yeyuno/metabolismo , Ácido Linoleico/química , Masculino , Ratones , Ácido Palmítico/química , Páncreas/efectos de los fármacos , Ratas , Ratas Wistar , Ácidos Esteáricos/química
7.
Molecules ; 26(5)2021 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-33800074

RESUMEN

The present study aimed to investigate the effects of mungbean water extract (MWE) on insulin downstream signaling in insulin-resistant HepG2 cells. Whole seed mungbean was extracted using boiling water, mimicking a traditional cooking method. Vitexin and isovitexin were identified in MWE. The results showed that MWE inhibited protein tyrosine phosphatase (PTP)-1B (IC50 = 10 µg/mL), a negative regulator of insulin signaling. MWE enhanced cellular glucose uptake and altered expression of genes involved in glucose metabolism, including forkhead box O1 (FOXO1), phosphoenolpyruvate carboxykinase (PEPCK), and glycogen synthase kinase (GSK)-3ß in the insulin-resistant HepG2 cells. In addition, MWE inhibited both α-amylase (IC50 = 36.65 mg/mL) and α-glucosidase (IC50 = 3.07 mg/mL). MWE also inhibited the formation of advanced glycation end products (AGEs) (IC50 = 2.28 mg/mL). This is the first study to show that mungbean water extract increased cellular glucose uptake and improved insulin sensitivity of insulin-resistant HepG2 cells through PTP-1B inhibition and modulating the expression of genes related to glucose metabolism. This suggests that mungbean water extract has the potential to be a functional ingredient for diabetes.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Extractos Vegetales/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Vigna/química , Inhibidores Enzimáticos/química , Flavonoides/análisis , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/genética , Glucosa/farmacocinética , Productos Finales de Glicación Avanzada/efectos de los fármacos , Productos Finales de Glicación Avanzada/metabolismo , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Células Hep G2 , Humanos , Insulina/farmacología , Fenoles/análisis , Extractos Vegetales/química , Temperatura , Agua/química , alfa-Amilasas/antagonistas & inhibidores
8.
Front Endocrinol (Lausanne) ; 12: 611147, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33828527

RESUMEN

Glucagon is secreted from the pancreatic alpha cells and plays an important role in the maintenance of glucose homeostasis, by interacting with insulin. The plasma glucose levels determine whether glucagon secretion or insulin secretion is activated or inhibited. Despite its relevance, some aspects of glucagon secretion and kinetics remain unclear. To gain insight into this, we aimed to develop a mathematical model of the glucagon kinetics during an oral glucose tolerance test, which is sufficiently simple to be used in the clinical practice. The proposed model included two first-order differential equations -one describing glucagon and the other describing C-peptide in a compartment remote from plasma - and yielded a parameter of possible clinical relevance (i.e., SGLUCA(t), glucagon-inhibition sensitivity to glucose-induced insulin secretion). Model was validated on mean glucagon data derived from the scientific literature, yielding values for SGLUCA(t) ranging from -15.03 to 2.75 (ng of glucagon·nmol of C-peptide-1). A further validation on a total of 100 virtual subjects provided reliable results (mean residuals between -1.5 and 1.5 ng·L-1) and a negative significant linear correlation (r = -0.74, p < 0.0001, 95% CI: -0.82 - -0.64) between SGLUCA(t) and the ratio between the areas under the curve of suprabasal remote C-peptide and glucagon. Model reliability was also proven by the ability to capture different patterns in glucagon kinetics. In conclusion, the proposed model reliably reproduces glucagon kinetics and is characterized by sufficient simplicity to be possibly used in the clinical practice, for the estimation in the single individual of some glucagon-related parameters.


Asunto(s)
Células Secretoras de Glucagón/efectos de los fármacos , Glucagón/metabolismo , Insulina/farmacología , Modelos Teóricos , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Glucagón/antagonistas & inhibidores , Células Secretoras de Glucagón/metabolismo , Glucosa/farmacocinética , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina/fisiología , Secreción de Insulina/fisiología , Cinética
10.
Diabetes ; 70(6): 1292-1302, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33757993

RESUMEN

Hepatic glucose uptake (HGU) is critical for maintaining normal postprandial glucose metabolism. Insulin is clearly a key regulator of HGU, but the physiologic mechanisms by which it acts have yet to be established. This study sought to determine the mechanisms by which insulin regulates liver glucose uptake under postprandial-like conditions (hyperinsulinemia, hyperglycemia, and a positive portal vein-to-arterial glucose gradient). Portal vein insulin infusion increased hepatic insulin levels fivefold in healthy dogs. In one group (n = 7), the physiologic response was allowed to fully occur, while in another (n = 7), insulin's indirect hepatic effects, occurring secondary to its actions on adipose tissue, pancreas, and brain, were blocked. This was accomplished by infusing triglyceride (intravenous), glucagon (portal vein), and inhibitors of brain insulin action (intracerebroventricular) to prevent decreases in plasma free fatty acids or glucagon, while blocking increased hypothalamic insulin signaling for 4 h. In contrast to the indirect hepatic effects of insulin, which were previously shown capable of independently generating a half-maximal stimulation of HGU, direct hepatic insulin action was by itself able to fully stimulate HGU. This suggests that under hyperinsulinemic/hyperglycemic conditions insulin's indirect effects are redundant to direct engagement of hepatocyte insulin receptors.


Asunto(s)
Glucosa/farmacocinética , Insulina/farmacología , Hígado/metabolismo , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Perros , Ingestión de Alimentos/fisiología , Femenino , Hígado/efectos de los fármacos , Masculino , Comidas/fisiología , Transducción de Señal/efectos de los fármacos
11.
Diabetes ; 70(6): 1265-1277, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33674408

RESUMEN

While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by 18F-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.


Asunto(s)
Encéfalo/fisiología , Derivación Gástrica , Obesidad Mórbida , Adolescente , Adulto , Glucemia/metabolismo , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Cognición/fisiología , Femenino , Derivación Gástrica/efectos adversos , Glucosa/farmacocinética , Humanos , Hipoglucemia/etiología , Hipoglucemia/metabolismo , Hipoglucemia/psicología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuronas/fisiología , Obesidad Mórbida/metabolismo , Obesidad Mórbida/psicología , Obesidad Mórbida/cirugía , Tomografía de Emisión de Positrones , Flujo Sanguíneo Regional/fisiología , Adulto Joven
12.
Nat Commun ; 12(1): 658, 2021 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-33510169

RESUMEN

A microneedle array is an attractive option for a minimally invasive means to break through the skin barrier for efficient transdermal drug delivery. Here, we report the applications of solid polymer-based ion-conductive porous microneedles (PMN) containing interconnected micropores for improving iontophoresis, which is a technique of enhancing transdermal molecular transport by a direct current through the skin. The PMN modified with a charged hydrogel brings three innovative advantages in iontophoresis at once: (1) lowering the transdermal resistance by low-invasive puncture of the highly resistive stratum corneum, (2) transporting of larger molecules through the interconnected micropores, and (3) generating electroosmotic flow (EOF). In particular, the PMN-generated EOF greatly enhances the transdermal molecular penetration or extraction, similarly to the flow induced by external pressure. The enhanced efficiencies of the EOF-assisted delivery of a model drug (dextran) and of the extraction of glucose are demonstrated using a pig skin sample. Furthermore, the powering of the PMN-based transdermal EOF system by a built-in enzymatic biobattery (fructose / O2 battery) is also demonstrated as a possible totally organic iontophoresis patch.


Asunto(s)
Sistemas de Liberación de Medicamentos/instrumentación , Sistemas de Liberación de Medicamentos/métodos , Epidermis/metabolismo , Piel/metabolismo , Administración Cutánea , Animales , Dextranos/administración & dosificación , Dextranos/metabolismo , Dextranos/farmacocinética , Electroósmosis , Fluoresceína-5-Isotiocianato/administración & dosificación , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Fluoresceína-5-Isotiocianato/farmacocinética , Glucosa/administración & dosificación , Glucosa/metabolismo , Glucosa/farmacocinética , Humanos , Iontoforesis/instrumentación , Iontoforesis/métodos , Masculino , Microinyecciones , Agujas , Moléculas de Patrón Molecular Asociado a Patógenos/administración & dosificación , Moléculas de Patrón Molecular Asociado a Patógenos/metabolismo , Moléculas de Patrón Molecular Asociado a Patógenos/farmacocinética , Porosidad , Porcinos
13.
Diabetologia ; 64(5): 1158-1168, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33511440

RESUMEN

AIMS/HYPOTHESIS: It has been proposed that muscle fibre type composition and perfusion are key determinants of insulin-stimulated muscle glucose uptake, and alterations in muscle fibre type composition and perfusion contribute to muscle, and consequently whole-body, insulin resistance in people with obesity. The goal of the study was to evaluate the relationships among muscle fibre type composition, perfusion and insulin-stimulated glucose uptake rates in healthy, lean people and people with obesity. METHODS: We measured insulin-stimulated whole-body glucose disposal and glucose uptake and perfusion rates in five major muscle groups (erector spinae, obliques, rectus abdominis, hamstrings, quadriceps) in 15 healthy lean people and 37 people with obesity by using the hyperinsulinaemic-euglycaemic clamp procedure in conjunction with [2H]glucose tracer infusion (to assess whole-body glucose disposal) and positron emission tomography after injections of [15O]H2O (to assess muscle perfusion) and [18F]fluorodeoxyglucose (to assess muscle glucose uptake). A biopsy from the vastus lateralis was obtained to assess fibre type composition. RESULTS: We found: (1) a twofold difference in glucose uptake rates among muscles in both the lean and obese groups (rectus abdominis: 67 [51, 78] and 32 [21, 55] µmol kg-1 min-1 in the lean and obese groups, respectively; erector spinae: 134 [103, 160] and 66 [24, 129] µmol kg-1 min-1, respectively; median [IQR]) that was unrelated to perfusion or fibre type composition (assessed in the vastus only); (2) the impairment in insulin action in the obese compared with the lean group was not different among muscle groups; and (3) insulin-stimulated whole-body glucose disposal expressed per kg fat-free mass was linearly related with muscle glucose uptake rate (r2 = 0.65, p < 0.05). CONCLUSIONS/INTERPRETATION: Obesity-associated insulin resistance is generalised across all major muscles, and is not caused by alterations in muscle fibre type composition or perfusion. In addition, insulin-stimulated whole-body glucose disposal relative to fat-free mass provides a reliable index of muscle glucose uptake rate.


Asunto(s)
Glucosa/metabolismo , Insulina/farmacología , Músculo Esquelético/efectos de los fármacos , Obesidad/metabolismo , Delgadez/metabolismo , Adulto , Transporte Biológico/efectos de los fármacos , Biopsia , Femenino , Fluorodesoxiglucosa F18 , Glucosa/farmacocinética , Técnica de Clampeo de la Glucosa , Humanos , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Masculino , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Obesidad/diagnóstico por imagen , Obesidad/patología , Tomografía de Emisión de Positrones , Músculo Cuádriceps/diagnóstico por imagen , Músculo Cuádriceps/efectos de los fármacos , Músculo Cuádriceps/metabolismo , Músculo Cuádriceps/patología , Delgadez/diagnóstico por imagen , Delgadez/patología
14.
Food Chem ; 340: 127908, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-32889206

RESUMEN

This study aims to evaluate the effects of in vitro digestion of rice and common bean blends on phenolics content and profile. Black and carioca beans were used as common bean sources. Blends consisted of 25:75, 50:50, and 75:25 polished rice:beans (w/w). Pure rice or pure beans were also analyzed. Phenolic compounds were determined in raw, cooked, and digested samples. The glucose release through in vitro digestion was slower as the proportion of black beans or carioca beans increased. Starch digestibility ranged between 41.1 in 100% carioca bean to 84.4% in 100% rice. Hydroxybenzoic acid, ferulic acid, p-coumaric acid, catechin, and epicatechin were the most abundant phenolics detected in the studied samples. Considering the content of phenolic compounds determined in the raw, cooked, and digested grains, only a small fraction was available for absorption in the gut, with amounts varying from 0.1 to 0.6 µg·g-1.


Asunto(s)
Oryza/química , Phaseolus/química , Fenoles/análisis , Almidón/química , Almidón/farmacocinética , Catequina/análisis , Catequina/química , Culinaria , Digestión , Glucosa/farmacocinética , Hidroxibenzoatos/análisis , Hidroxibenzoatos/química , Fenoles/química , Almidón/análisis
15.
Food Chem ; 341(Pt 1): 128148, 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33038776

RESUMEN

The brown seaweed Undaria pinnatifida polysaccharides show various biological activities, but their hypoglycemic activity and the underlying mechanism remain unclear. Here, three fractions of sulfated polysaccharides Up-3, Up-4, and Up-5 were prepared by microwave-assisted extraction from U. pinnatifida. In vitro assays demonstrated that Up-3 and Up-4 had strong α-glucosidase inhibitory activity, and Up-3, Up-4, and Up-5 could improve the glucose uptake in insulin-resistant HepG2 cells without affecting their viability. In vivo studies indicated Up-3 and Up-4 markedly reduced postprandial blood glucose levels. Up-U (a mixture of Up-3, Up-4, and Up-5), reduced fasting blood glucose levels, increased glucose tolerance and alleviated insulin resistance in HFD/STZ-induced hyperglycemic mice. Histopathological observation and hepatic glycogen measurement showed that Up-U alleviated the damage of the pancreas islet cell, reduced hepatic steatosis, and promoted hepatic glycogen synthesis. These findings suggest that Up-U could alleviate postprandial and HFD/STZ-induced hyperglycemia and was a potential agent for diabetes treatment.


Asunto(s)
Hipoglucemiantes/farmacología , Polisacáridos/farmacología , Algas Marinas/química , Undaria/química , Animales , Fraccionamiento Químico , Dieta Alta en Grasa/efectos adversos , Glucosa/metabolismo , Glucosa/farmacocinética , Células Hep G2 , Humanos , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/etiología , Hipoglucemiantes/química , Insulina/farmacología , Resistencia a la Insulina , Masculino , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Microondas , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Periodo Posprandial , Sulfatos/química
16.
J Clin Pharmacol ; 61(1): 116-124, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32729150

RESUMEN

The integrated minimal model allows assessment of clinical diagnosis indices, for example, insulin sensitivity (SI ) and glucose effectiveness (SG ), from data of the insulin-modified intravenous glucose tolerance test (IVGTT), which is laborious with an intense sampling schedule, up to 32 samples. The aim of this study was to propose a more informative, although less laborious, IVGTT design to be used for model-based assessment of SI and SG . The IVGTT design was optimized simultaneously for all design variables: glucose and insulin infusion doses, time of glucose dose and start of insulin infusion, insulin infusion duration, sampling times, and number of samples. Design efficiency was used to compare among different designs. The simultaneously optimized designs showed a profound higher efficiency than both standard rich (32 samples) and sparse (10 samples) designs. The optimized designs, after removing replicate sample times, were 1.9 and 7.1 times more efficient than the standard rich and sparse designs, respectively. After including practical aspects of the designs, for example, sufficient duration between samples and avoidance of prolonged hypoglycemia, we propose 2 practical designs with fewer sampling times and lower input of glucose and insulin than standard designs, constrained to prevent hypoglycemia. The optimized practical rich design is equally efficient in assessing SI and SG as the rich standard design, but with half the number of the samples, while the optimized practical sparse design has 1 less sample and requires 4.6 times fewer individuals for equal certainty when assessing SI and SG than the sparse standard design.


Asunto(s)
Prueba de Tolerancia a la Glucosa/métodos , Resistencia a la Insulina/fisiología , Esquema de Medicación , Glucosa/administración & dosificación , Glucosa/farmacocinética , Humanos , Insulina/administración & dosificación , Insulina/farmacocinética , Modelos Biológicos
17.
Am J Physiol Endocrinol Metab ; 320(3): E425-E437, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33356994

RESUMEN

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


Asunto(s)
Diabetes Mellitus Tipo 1/metabolismo , Ejercicio Físico/fisiología , Glucosa/farmacocinética , Insulina/fisiología , Adolescente , Adulto , Glucemia/metabolismo , Femenino , Humanos , Hiperinsulinismo/metabolismo , Hipoglucemia/metabolismo , Insulina/administración & dosificación , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Masculino , Persona de Mediana Edad , Esfuerzo Físico/fisiología , Adulto Joven
18.
Reprod Biol Endocrinol ; 18(1): 117, 2020 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-33218355

RESUMEN

BACKGROUND: Solute carrier family 2 member 1 (SLC2A1; previously known as glucose transporter 1), is the most abundant glucose transporter in human endometrium and is up-regulated during decidualization, whereas high insulin may have a negative impact on this process. The present study aimed to investigate the effect of insulin on the expression of SLC2A1 and glucose uptake in decidualizing human endometrial stromal cells. METHODS: We induced in vitro decidualization of endometrial stromal cells obtained from regularly menstruating healthy non-obese women. The cells were treated with increasing concentrations of insulin, and the involvement of the transcription factor forkhead box O1 (FOXO1) was evaluated using a FOXO1 inhibitor. SLC2A1 mRNA levels were measured by Real-Time PCR and protein levels were evaluated by immunocytochemistry. Glucose uptake was estimated by an assay quantifying the cellular uptake of radioactive glucose. One-way ANOVA, Dunnett's multiple comparisons test and paired t-test were used to determine the statistical significance of the results. RESULTS: We found that insulin dose-dependently decreased SLC2A1 mRNA levels and decreased protein levels of SLC2A1 in decidualizing human endometrial stromal cells. Transcriptional inactivation of FOXO1 seems to explain at least partly the down-regulation of SLC2A1 by insulin. Glucose uptake increased upon decidualization, whereas insulin treatment resulted in a slight inhibition of the glucose uptake, although not significant for all insulin concentrations. CONCLUSIONS: These results indicate an impairment of decidualization by high concentrations of insulin. Future studies will determine the clinical significance of our results for endometrial function and decidualization in women with insulin resistance and hyperinsulinemia.


Asunto(s)
Expresión Génica/efectos de los fármacos , Transportador de Glucosa de Tipo 1/genética , Glucosa/metabolismo , Insulina/farmacología , Células del Estroma/efectos de los fármacos , Adulto , Células Cultivadas , Decidua/fisiología , Regulación hacia Abajo/efectos de los fármacos , Endometrio/citología , Femenino , Glucosa/farmacocinética , Transportador de Glucosa de Tipo 1/metabolismo , Humanos , Hipoglucemiantes/farmacología , Inmunohistoquímica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células del Estroma/metabolismo , Adulto Joven
19.
Nutrients ; 12(10)2020 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-33003504

RESUMEN

Obesity is an alarming yet increasing phenomenon worldwide, and more effective obesity management strategies have become essential. In addition to the numerous anti-adipogenic treatments promising a restauration of a healthy white adipose tissue (WAT) function, numerous studies reported on the critical role of nutritional parameters in obesity development. In a metabolic disorder context, a better control of nutrient intake is a key step in slowing down adipogenesis and therefore obesity. Of interest, the effect on WAT remodeling deserves deeper investigations. Among the different actors of WAT plasticity, the mitochondrial network plays a central role due to its dynamics and essential cellular functions. Hence, the present in vitro study, conducted on the 3T3-L1 cell line, aimed at evaluating the incidence of modulating the carbohydrates intake on adipogenesis through an integrated assessment of mitochondrial structure, dynamics, and functions-correlated changes. For this purpose, our experimental strategy was to compare the occurrence of adipogenesis in 3T3-L1 cells cultured either in a high-glucose (HG) medium (25 mM) or in a low-glucose (LG) medium (5 mM) supplemented with equivalent galactose (GAL) levels (20 mM). The present LG-GAL condition was associated, in differentiating adipocytes, to a reduced lipid droplet network, lower expressions of early and late adipogenic genes and proteins, an increased mitochondrial network with higher biogenesis marker expression, an equilibrium in the mitochondrial fusion/fission pattern, and a decreased expression of mitochondrial metabolic overload protein markers. Therefore, those main findings show a clear effect of modulating glucose accessibility on 3T3-L1 adipogenesis through a combined effect of adipogenesis modulation and overall improvement of the mitochondrial health status. This nutritional approach offers promising opportunities in the control and prevention of obesity.


Asunto(s)
Adipogénesis/efectos de los fármacos , Carbohidratos de la Dieta/farmacocinética , Ingestión de Alimentos/fisiología , Mitocondrias/efectos de los fármacos , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Animales , Disponibilidad Biológica , Galactosa/farmacocinética , Glucosa/farmacocinética , Ratones
20.
Molecules ; 25(20)2020 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-33066298

RESUMEN

Protein-tyrosine phosphatase 1B (PTP1B) has been considered as a promising target for treating insulin resistance. In searching for naturally occurring PTB1B antagonists, two new pimarane diterpenoids, named 2α-hydroxy-7-oxo-pimara-8(9),15-diene (1) and 19-hydroxy-2α-acetoxy-7-oxo-pimara-8(9),15-diene (2), were isolated from the seeds of Caesalpinia minax. Their structures were determined by extensive analysis of NMR and HR-ESIMS data, and their absolute configurations were determined by electronic circular dichroism (ECD) spectra. Compound 1 was disclosed as a competitive inhibitor of PTP1B with an IC50 (the half-maximal inhibitory concentration) value of 19.44 ± 2.39 µM and a Ki (inhibition constant) value of 13.69 ± 2.72 µM. Moreover, compound 1 dose-dependently promoted insulin-stimulated glucose uptake in C2C12 myotubes through activating insulin signaling pathway. Compound 1 might be further developed as an insulin sensitizer.


Asunto(s)
Abietanos/química , Abietanos/farmacología , Caesalpinia/química , Insulina/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Animales , Dicroismo Circular , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Glucosa/farmacocinética , Insulina/farmacología , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Semillas/química , Espectrometría de Masa por Ionización de Electrospray
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