Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56.860
Filtrar
Mais filtros








Intervalo de ano de publicação
1.
J Diabetes Res ; 2022: 9537741, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242882

RESUMO

BACKGROUND: Several experimental studies have suggested beneficial effects of Ceriporia lacerata on glucose metabolism. However, there has been no human study assessing the effects of C. lacerata on glucose metabolism. Therefore, we investigated whether C. lacerata improves glucose control and insulin resistance in type 2 diabetes patients. METHODS: Ninety patients diagnosed with type 2 diabetes (T2DM) for more than 6 months were enrolled. Subjects were randomly divided into placebo (n = 45) or C. lacerata (n = 45) groups and then assigned to take placebo or C. lacerata capsules (500 mg/capsule) for a 12-week intervention period. Biochemical markers, including fasting glucose, 2-hour postprandial plasma glucose, and lipid profile levels, as well as insulin, c-peptide, and Hba1c, were measured. Furthermore, insulin sensitivity indices, such as HOMA-IR, HOMA-beta, and QUICKI, were assessed before and after the 12-week administration. RESULTS: Eighty-four patients completed the study. There were no significant differences in fasting, postprandial glucose, HbA1c, or lipid parameters. HOMA-IR and QUICKI indices were improved at week 12 in the C. lacerata group, especially in subjects with HOMA-IR of 1.8 or more (p < 0.05). Fasting, postprandial c-peptide, and insulin levels decreased at week 12 in the C. lacerata group (p < 0.05). These significant differences were not observed in the placebo group. CONCLUSION: Twelve-week administration of C. lacerata in T2DM patients resulted in significant improvement in insulin resistance, especially in those with lower insulin sensitivity. A larger population study with a longer follow-up period and an effort to elucidate the mechanism is warranted to further assess the effects of C. lacerata on T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Resistência à Insulina/fisiologia , Extratos Vegetais/farmacologia , Polyporales/metabolismo , Adulto , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/metabolismo , Extratos Vegetais/uso terapêutico
2.
Dis Markers ; 2022: 6777283, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295321

RESUMO

Background: The effects of weight loss therapies on omentin-1 levels have been unclear, showing both elevations and decreases in circulating levels. The role of dietary fat might have an important role. The aim of our investigation was to evaluate the influence of weight decrease on omentin-1 levels after two different high-fat hypocaloric diets. Methods: 319 Caucasian obese subjects were randomly allocated during 12 weeks (Diet M (high monounsaturated fat diet) vs. Diet P (high polyunsaturated fat diet)). The mean age was 47.2 ± 5.0 years (range: 26-64), and the mean body mass index (BMI) was 37.9 ± 4.1 kg/m2 (range: 30.6-39.8). Sex distribution was 237 females (74.7%) and 72 males (25.3%). Anthropometric and biochemical parameters were evaluated at basal and after both diets. SPSS 23.0 has been used to realize univariant and multivariant statistical analysis. Results: After both diets, BMI, weight, fat mass, waist circumference, systolic blood, LDL-cholesterol, insulin levels, and HOMA-IR decreased in a statistical way from basal values. These improvements were similar in both diets. After Diet P, omentin-1 levels increase (21.2 ± 9.1 ng/ml: P = 0.02), and after Diet M, this adipokine increases (47.1 ± 11.2 ng/ml: P = 0.02), too. The increase of omentin-1 with Diet M was statistically significantly higher than that after Diet P (P = 0.01). A multiple regression analyses adjusted by age and sex reported a statistical relation between BMI (kg/m2) and insulin (UI/L) with omentin-1 levels. Conclusions: Our study demonstrated a significant improvement on serum omentin-1 levels after weight loss secondary to both diets; in contrast, omentin-1 improvement was higher with Diet M than with Diet P.


Assuntos
Dieta Hiperlipídica , Dieta Redutora , Obesidade/sangue , Obesidade/dietoterapia , Perda de Peso , Adipocinas/metabolismo , Índice de Massa Corporal , Citocinas/sangue , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Insulina/sangue , Lectinas/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/genética
3.
Artigo em Inglês | MEDLINE | ID: mdl-35247678

RESUMO

Insulin is a peptide hormone that is secreted by the ß cells of the pancreas and is essential to the metabolism of carbohydrates, fats, and proteins in the body. The marmoset insulin peptide is not homologous with human insulin and therefore commonly available assays do not work for this species. Due to the increasing popularity of marmoset research, a simple, specific assay for the quantitation of marmoset insulin is needed. This study aimed to develop and validate a bottom-up proteomic workflow with trypsin digestion and analysis using LC coupled with triple quadrupole mass spectrometry (LC-MS/MS). Marmoset serum proteins were subjected to denaturation, reduction, and enzymatic cleavage to extract a unique, 7 amino acid peptide for quantitation of marmoset insulin. Resolution of the peptide was achieved by LC-MS/MS using electrospray ionization operating in positive mode. Calibration was achieved by aliquot dilution of fully synthetic marmoset insulin tryptic peptide into macaque serum. A stable-isotope labeled (13C, 15N) synthetic marmoset insulin tryptic peptide was used as internal standard. The assay was fully validated according to bioanalytical method validation guidelines for linearity, precision, and dilution linearity using purified marmoset insulin. The limit of detection was 15.49 pmol/L and the limit of quantitation was 140.78 pmol/L. Biological validation was achieved by comparison of samples previously run by radioimmunoassay and measurement of the marmoset insulin response to glucose via an oral glucose tolerance test (OGTT). The physiological range of marmoset insulin was shown to be 84.5 to 1222 pmol/L. In summary, this paper presents a simple, reproducible method to measure marmoset insulin in serum using LC-MS/MS.


Assuntos
Callithrix/fisiologia , Cromatografia Líquida/métodos , Insulina/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Modelos Animais de Doenças , Feminino , Limite de Detecção , Modelos Lineares , Masculino , Síndrome Metabólica , Reprodutibilidade dos Testes
4.
BMC Endocr Disord ; 22(1): 58, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35255873

RESUMO

BACKGROUNDS: In recent years, many studies have shown that insulin resistance is related to the occurrence of thyroid cancer, but there are few reports on whether the two are related under the premise that thyroid function is normal and the metabolic components related to insulin resistance are excluded. This study aims to analyze the insulin resistance of patients with differentiated thyroid cancer after excluding the population with abnormal metabolic components, and to study the risk factors of thyroid cancer in this population. METHODS: 61 subjects diagnosed with differentiated thyroid carcinoma (DTC) formed the DTC group and 262 subjects with benign nodules formed the control group. Body mass index (BMI, kg/m2), waist circumference (WC), lipid profiles, and free T3 (FT3), free T4 (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroid globulin antibody (TGAb), alanine transaminase (ALT), aspartate aminotransferase (AST), fasting plasma glucose (FPG), fasting serum insulin and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured. RESULTS: Mean subjects age (P = 0.021), BMI (P = 0.049), WC (P = 0.01), serum insulin concentration (P = 0.006), and HOMA-IR level (P = 0.005) were significantly greater in the DTC group than in the control group. Multivariate binary logistic regression analysis identified advanced age (OR = 1.027 [1.003-1.051], P = 0.029) and an increased HOMA-IR level (OR = 1.572 [1.277-1.935], P < 0.001) as significant risk factors for thyroid cancer. CONCLUSIONS: IR may increase the risk of thyroid cancer development even in the absence of conditions affecting insulin resistance.


Assuntos
Resistência à Insulina/fisiologia , Neoplasias da Glândula Tireoide/epidemiologia , Adulto , Fatores Etários , Idoso , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Circunferência da Cintura
5.
Mar Drugs ; 20(3)2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35323474

RESUMO

The objective of the present study was to test whether a brown seaweed extract rich in polyphenols combined with a low-calorie diet would induce additional weight loss and improve blood glucose homeostasis in association with a metabolic and inflammatory response in overweight/obese prediabetic subjects. Fifty-six overweight/obese, dysglycemic, and insulin-resistant men and women completed a randomized, placebo-controlled, double-blind, and parallel clinical trial. Subjects were administrated 500 mg/d of either brown seaweed extract or placebo combined with individualized nutritional advice for moderate weight loss over a period of 12 weeks. Glycemic, anthropometric, blood pressure, heart rate, body composition, lipid profile, gut integrity, and oxidative and inflammatory markers were measured before and at the end of the trial. No effect was observed on blood glucose. We observed significant but small decreases in plasma C-peptide at 120 min during 2 h-OGTT (3218 ± 181 at pre-intervention vs. 2865 ± 186 pmol/L at post-intervention in the brown seaweed group; 3004 ± 199 at pre-intervention vs. 2954 ± 179 pmol/L at post-intervention in the placebo group; changes between the two groups, p = 0.002), heart rate (72 ± 10 at pre-intervention vs. 69 ± 9 (n/min) at post-intervention in the brown seaweed group; 68 ± 9 at pre-intervention vs. 68 ± 8 (n/min) at post-intervention in the placebo group; changes between the two groups, p = 0.01), and an inhibition in the increase of pro-inflammatory interleukin-6 (IL-6) (1.3 ± 0.7 at pre-intervention vs. 1.5 ± 0.7 pg/L at post-intervention in the brown seaweed group; 1.4 ± 1.1 at pre-intervention vs. 2.2 ± 1.6 pg/L at post-intervention in the placebo group; changes between the two groups, p = 0.02) following brown seaweed consumption compared with placebo in the context of moderate weight loss. Although consumption of brown seaweed extract had no effect on body weight or blood glucose, an early attenuation of the inflammatory response was observed in association with marginal changes in metabolic parameters related to the prevention of diabetes type 2.


Assuntos
Anti-Inflamatórios/uso terapêutico , Ascophyllum/química , Misturas Complexas/uso terapêutico , Fucus/química , Sobrepeso/tratamento farmacológico , Polifenóis/uso terapêutico , Estado Pré-Diabético/tratamento farmacológico , Alga Marinha/química , Adolescente , Adulto , Idoso , Glicemia/efeitos dos fármacos , Peptídeo C/sangue , Dieta com Restrição de Gorduras , Método Duplo-Cego , Feminino , Humanos , Insulina/sangue , Interleucina-6/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Sobrepeso/sangue , Estado Pré-Diabético/sangue , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos , Adulto Jovem
6.
Acta Med Okayama ; 76(1): 51-56, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35236998

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine metabolic disorder that is associated with high insulin resistance and obesity. However, ~70% of women with PCOS in Japan are non-obese. We retrospectively analyzed the cases of 163 Japanese women with PCOS who visited our Ob/Gyn department in 2006-2018 to determine which has a greater effect on insulin resistance: PCOS or obesity. We reviewed the women's medical records and calculated their insulin resistance and insulin secretion. The women's mean age and pre-pregnancy body mass index (BMI) were 30±5.8 years and 24.8±5.6 kg/m2, respectively; their mean ± SD fasting plasma glucose, 94.1±13.7 mg/dL; HOMA-IR, 2.1±2.0; QUICKI, 0.4±0.0; and HOMA-ß, 108.9±88.0%. Sixtyeight women were pregnant, and 37% (n=25) were obese (BMI ≥ 25 kg/m2). Obesity had a greater effect on insulin resistance: fasting plasma glucose F(1, 53)=6.134, p<0.05; fasting insulin F(1, 53)=31.606, p<0.01; HOMA-IR F(1, 53)=31.670, p<0.01; QUICKI F(1, 53)=16.156, p<0.01. There was no significant difference in values other than QUICKI and testosterone between the women with and without PCOS. Obesity thus had a greater effect on increased insulin resistance in pregnant women with PCOS. Further studies of the insulin resistance of non-obese women with PCOS is needed, as non-obese women with PCOS are common in Asia.


Assuntos
Resistência à Insulina/fisiologia , Obesidade/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Glicemia , Índice de Massa Corporal , Jejum , Feminino , Humanos , Insulina/sangue , Japão , Gravidez , Estudos Retrospectivos , Testosterona/sangue , Adulto Jovem
7.
Proc Natl Acad Sci U S A ; 119(7)2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35145023

RESUMO

Insulin resistance and ß-cell dysfunction are two main molecular bases yet to be further elucidated for type 2 diabetes (T2D). Accumulating evidence indicates that stimulator of interferon genes (STING) plays an important role in regulating insulin sensitivity. However, its function in ß-cells remains unknown. Herein, using global STING knockout (STING-/-) and ß-cell-specific STING knockout (STING-ßKO) mouse models, we revealed a distinct role of STING in the regulation of glucose homeostasis through peripheral tissues and ß-cells. Specially, although STING-/- beneficially alleviated insulin resistance and glucose intolerance induced by high-fat diet, it surprisingly impaired islet glucose-stimulated insulin secretion (GSIS). Importantly, STING is decreased in islets of db/db mice and patients with T2D, suggesting a possible role of STING in ß-cell dysfunction. Indeed, STING-ßKO caused glucose intolerance due to impaired GSIS, indicating that STING is required for normal ß-cell function. Islet transcriptome analysis showed that STING deficiency decreased expression of ß-cell function-related genes, including Glut2, Kcnj11, and Abcc8, contributing to impaired GSIS. Mechanistically, the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and cleavage under targets and tagmentation (CUT&Tag) analyses suggested that Pax6 was the transcription factor that might be associated with defective GSIS in STING-ßKO mice. Indeed, Pax6 messenger RNA and protein levels were down-regulated and its nuclear localization was lost in STING-ßKO ß-cells. Together, these data revealed a function of STING in the regulation of insulin secretion and established pathophysiological significance of fine-tuned STING within ß-cells and insulin target tissues for maintaining glucose homeostasis.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Intolerância à Glucose/induzido quimicamente , Glucose/metabolismo , Insulina/metabolismo , Proteínas de Membrana/metabolismo , Animais , Diabetes Mellitus Experimental , Dieta Hiperlipídica/efeitos adversos , Regulação para Baixo , Regulação da Expressão Gênica , Homeostase , Humanos , Insulina/sangue , Resistência à Insulina , Células Secretoras de Insulina , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout
8.
J Diabetes Res ; 2022: 7153238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35103244

RESUMO

INTRODUCTION: Adipose tissue (AT) expandability may be facilitated by adiponectin and suppressed by orosomucoid, and reduced AT expandability may be associated with first-degree relatives of type 2 diabetes. We tested the hypothesis that orosomucoid may be associated not only with adiponectin and adipose tissue insulin resistance but also with a family history of type 2 diabetes (FHD). Research Design and Methods. Anthropometric and metabolic variables, adipokines, and measures of inflammatory and insulin resistance were cross-sectionally investigated in 153 young normal weight Japanese women. Stepwise multivariate linear regression analyses were used to identify the most important determinants of orosomucoid. RESULTS: Orosomucoid was higher in women with positive (n = 57) compared to women with negative FHD and was associated positively with FHD (both p = 0.01). Orosomucoid also showed positive associations with fasting glucose (p < 0.001), free fatty acids (p = 0.001), and HbA1c (p = 0.007), whereas there was no association with fasting insulin and serum lipids. In addition, orosomucoid was associated inversely with adiponectin (p = 0.02) and positively with adipose tissue-insulin resistance index (AT-IR, the product of fasting insulin and free fatty acids; p = 0.001) but not with homeostasis model assessment-insulin resistance, leptin, and high-sensitivity C-reactive protein. In multivariate analyses, AT-IR (standardized ß, 0.22; p = 0.003), serum adiponectin (standardized ß, -0.163; p = 0.032), FHD+ (standardized ß, 0.178; p = 0.029), and HbA1c (standardized ß, 0.213; p = 0.005) emerged as independent determinants of orosomucoid and explained 15.2% of its variability. CONCLUSIONS: These results are the first to demonstrate that orosomucoid is associated not only with adipose tissue-insulin resistance and adiponectin but also with FHD.


Assuntos
Adiponectina/análise , Diabetes Mellitus Tipo 2/diagnóstico , Resistência à Insulina/fisiologia , Orosomucoide/análise , Adiponectina/sangue , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Adulto , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Insulina/análise , Insulina/biossíntese , Insulina/sangue , Japão/epidemiologia , Masculino , Anamnese/métodos , Anamnese/estatística & dados numéricos , Pessoa de Meia-Idade , Orosomucoide/metabolismo
9.
J Diabetes Res ; 2022: 3250016, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35224106

RESUMO

This study investigates the effects of the water-soluble and organic-soluble Trichosanthes extracts on the hyperglycemic condition in streptozotocin- (STZ-) induced diabetic rats. The blood glucose levels, body weights, water intake, and urine volumes of rats in different experimental groups were monitored throughout the experiment, and the results obtained indicate that the two extracts can effectively reduce blood sugar levels, increase body weights, and improve water intake and urine volumes in diabetic rats. Based on blood biochemical analyses, the two extracts play an important role in regulating the diabetes-induced lipid metabolism disorder, increasing the levels of insulin and C-peptide, and alleviating the symptoms of diabetes. The variation in the liver glycogen contents of the water-soluble fraction and ethanol fraction groups suggests that the mechanisms underlying the hypoglycemic effects of the two extracts are different. Indeed, the water-soluble fraction alleviates diabetes symptoms in rats mainly by antioxidative activity, unlike the ethanol fraction.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Extratos Vegetais/metabolismo , Trichosanthes/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Modelos Animais de Doenças , Hipolipemiantes/metabolismo , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Insulina/sangue , Insulina/metabolismo , Insulina/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos
10.
PLoS One ; 17(2): e0263346, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35213542

RESUMO

AIMS: To investigate the association between BsmI and DM2 in patients with and without DR and to correlate with clinical parameters in a population in northeastern Brazil. METHODS: Cross-sectional case-control study in which data were collected from 285 individuals, including 128 patients with DM2 and 157 with DR. Clinical, biochemical and anthropometric parameters were analyzed, in addition to the single nucleotide polymorphism (SNP) BsmI of the VDR gene (rs1544410), genotyped by PCR-RFLP. RESULTS: In the DR group we found a greater number of patients using insulin therapy (p = 0.000) and with longer duration of DM2 (p = 0.000), in addition to higher serum creatinine values (p = 0.001). Higher fasting glucose levels and higher frequency of insulinoterapy were independently observed in patients with DR and b allele carriers, when compared to BB. CONCLUSION: The association of the bb/Bb genotypes (rs1544410) of the VDR gene with increased blood glucose levels and insulinoterapy may represent worse glicemic control in rs1544410 b allele carriers in DR Latin American individuals.


Assuntos
Retinopatia Diabética/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Receptores de Calcitriol/genética , Idoso , Alelos , Antropometria , Brasil/epidemiologia , Creatinina/sangue , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/patologia , Feminino , Genótipo , Humanos , Insulina/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/genética , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética
11.
Sci Rep ; 12(1): 1896, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35115614

RESUMO

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment is a therapeutic approach for type 2 diabetes mellitus (T2DM). Some reports have shown that SGLT2i treatment improves insulin resistance; however, few studies have evaluated insulin resistance by the glucose clamp method. Hepatic insulin clearance (HIC) is a new pathophysiological mechanism of T2DM. The effect of SGLT2i treatment on hepatic insulin clearance and insulin resistance is not well known. We investigated the effect of SGLT2i treatment on insulin resistance, insulin secretion, incretin levels, body composition, and hepatic insulin clearance. We conducted a meal tolerance test (MTT) and a hyperinsulinemic-euglycemic clamp test in 9 T2DM patients. Ipragliflozin (50 mg/day) was administered, and the MTT and clamp test were performed after 4 months. We calculated HIC as the postprandial C-peptide AUC-to-insulin AUC ratio. We also measured GLP-1, GIP, and glucagon levels during the MTT. Body weight and HbA1c were decreased, although not significantly, after 4 months of treatment. Postprandial glucose, fasting insulin and postprandial insulin were significantly decreased. Insulin resistance with the glucose clamp was not changed, but the HOMA-IR and insulin sensitivity indices were significantly improved. Incretin and glucagon levels were not changed. Hepatic insulin clearance was significantly increased, but whole-body insulin clearance was not changed. The FIB-4 index and fatty liver index were significantly reduced. The HOMA-beta and insulinogenic indices were not changed, but the C-peptide index was significantly increased. Although the number of patients was small, these results suggested that SGLT2i treatment improved liver function, decreased hepatic insulin resistance, and increased hepatic insulin clearance, despite the small weight reduction.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Resistência à Insulina , Insulina/sangue , Fígado/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Tiofenos/uso terapêutico , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Glucosídeos/efeitos adversos , Humanos , Japão , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Tiofenos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
12.
Int J Mol Sci ; 23(3)2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35162995

RESUMO

The unfolded protein response in the endoplasmic reticulum (UPRER) is involved in a number of metabolic diseases. Here, we characterize UPRER-induced metabolic changes in mouse livers in vivo through metabolic labeling and mass spectrometric analysis of lipid and proteome-wide fluxes. We induced UPRER by tunicamycin administration and measured synthesis rates of proteins, fatty acids and cholesterol, as well as RNA-seq. Contrary to reports in isolated cells, hepatic de novo lipogenesis and cholesterogenesis were markedly reduced, as were mRNA levels and synthesis rates of lipogenic proteins. H&E staining showed enrichment with lipid droplets while electron microscopy revealed ER morphological changes. Interestingly, the pre-labeling of adipose tissue prior to UPRER induction resulted in the redistribution of labeled fatty acids from adipose tissue to the liver, with replacement by unlabeled glycerol in the liver acylglycerides, indicating that the liver uptake was of free fatty acids, not whole glycerolipids. The redistribution of adipose fatty acids to the liver was not explicable by altered plasma insulin, increased fatty acid levels (lipolysis) or by reduced food intake. Synthesis of most liver proteins was suppressed under UPRER conditions, with the exception of BiP, other chaperones, protein disulfide isomerases, and proteins of ribosomal biogenesis. Protein synthesis rates generally, but not always, paralleled changes in mRNA. In summary, this combined approach, linking static changes with fluxes, revealed an integrated reduction of lipid and cholesterol synthesis pathways, from gene expression to translation and metabolic flux rates, under UPRER conditions. The reduced lipogenesis does not parallel human fatty liver disease. This approach provides powerful tools to characterize metabolic processes underlying hepatic UPRER in vivo.


Assuntos
Colesterol/metabolismo , Ácidos Graxos/sangue , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes/efeitos dos fármacos , Fígado/metabolismo , Tunicamicina/efeitos adversos , Tecido Adiposo/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Insulina/sangue , Lipogênese/efeitos dos fármacos , Masculino , Espectrometria de Massas , Camundongos , Modelos Animais , RNA-Seq , Resposta a Proteínas não Dobradas
13.
Artigo em Inglês | MEDLINE | ID: mdl-35219959

RESUMO

The gut microbiota (GM) and metabolites are important factors in mediating the development of type-2 diabetes mellitus (T2DM). An imbalance in the gut microbiota and metabolites can disrupt the function of the intestinal barrier, cause changes in the permeability of the intestinal mucosa and promote the immune inflammatory response, thereby aggravating the fluctuation of blood glucose level and promoting the occurrence and development of the chronic complications of DM. Manipulating the GM and metabolites is a promising therapeutic intervention and is being studied extensively. Shenqi compound (SQC) is a traditional Chinese medicine formulation, which has been widely used to improve T2DM. Studies have demonstrated that SQC can reduce glycemic variability, alleviate the inflammatory response, etc. However, its underlying mechanism remains unknown. Therefore, in this experiment, We administered SQC to Goto-Kakizaki (GK) rats and evaluated its effect on blood glucose homeostasis and the intestinal mucosal barrier. We identified the profiles of the GM and metabolites with the aid of 16S rDNA gene sequencing and non-target metabolomics analysis. It showed that SQC intervention could reduce glycemic variability, regulate serum levels of glucagon and insulin, and improve injury to the intestinal mucosal barrier of GK rats. In the gut, the ratio of bacteria of the phyla Bacteroidetes/Firmicutes could be improved after SQC intervention. SQC also regulated the relative abundance of Prevotellaceae, Butyricimonas, Bacteroides, Blautia, Roseburia, Lactobacillus, and Rothia. We found out that expression of 40 metabolites was significantly improved after SQC intervention. Further analyses of metabolic pathways indicated that the therapeutic effect of SQC might be related predominantly to its ability to improve gluconeogenesis/glycolysis, amino acid metabolism, lipid metabolism, citrate cycle, and butanoate metabolism. These results suggest that SQC may exert a beneficial role in T2DM by modulating the GM and metabolites in different pathways.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/microbiologia , Medicamentos de Ervas Chinesas/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Aminoácidos/metabolismo , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Gluconeogênese/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Humanos , Insulina/sangue , Masculino , Ratos , Ratos Wistar
14.
Nat Commun ; 13(1): 735, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35136059

RESUMO

Insulin receptor (Insr) protein is present at higher levels in pancreatic ß-cells than in most other tissues, but the consequences of ß-cell insulin resistance remain enigmatic. Here, we use an Ins1cre knock-in allele to delete Insr specifically in ß-cells of both female and male mice. We compare experimental mice to Ins1cre-containing littermate controls at multiple ages and on multiple diets. RNA-seq of purified recombined ß-cells reveals transcriptomic consequences of Insr loss, which differ between female and male mice. Action potential and calcium oscillation frequencies are increased in Insr knockout ß-cells from female, but not male mice, whereas only male ßInsrKO islets have reduced ATP-coupled oxygen consumption rate and reduced expression of genes involved in ATP synthesis. Female ßInsrKO and ßInsrHET mice exhibit elevated insulin release in ex vivo perifusion experiments, during hyperglycemic clamps, and following i.p. glucose challenge. Deletion of Insr does not alter ß-cell area up to 9 months of age, nor does it impair hyperglycemia-induced proliferation. Based on our data, we adapt a mathematical model to include ß-cell insulin resistance, which predicts that ß-cell Insr knockout improves glucose tolerance depending on the degree of whole-body insulin resistance. Indeed, glucose tolerance is significantly improved in female ßInsrKO and ßInsrHET mice compared to controls at 9, 21 and 39 weeks, and also in insulin-sensitive 4-week old males. We observe no improved glucose tolerance in older male mice or in high fat diet-fed mice, corroborating the prediction that global insulin resistance obscures the effects of ß-cell specific insulin resistance. The propensity for hyperinsulinemia is associated with mildly reduced fasting glucose and increased body weight. We further validate our main in vivo findings using an Ins1-CreERT transgenic line and find that male mice have improved glucose tolerance 4 weeks after tamoxifen-mediated Insr deletion. Collectively, our data show that ß-cell insulin resistance in the form of reduced ß-cell Insr contributes to hyperinsulinemia in the context of glucose stimulation, thereby improving glucose homeostasis in otherwise insulin sensitive sex, dietary and age contexts.


Assuntos
Diabetes Mellitus Tipo 2/genética , Hiperinsulinismo/genética , Resistência à Insulina/genética , Células Secretoras de Insulina/metabolismo , Receptor de Insulina/genética , Animais , Conjuntos de Dados como Assunto , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Técnicas de Introdução de Genes , Técnicas de Inativação de Genes , Glucose/metabolismo , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patologia , Insulina/sangue , Insulina/metabolismo , Células Secretoras de Insulina/patologia , Masculino , Camundongos , Camundongos Transgênicos , RNA-Seq , Receptor de Insulina/deficiência , Fatores Sexuais
15.
Retina ; 42(3): 442-449, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35188489

RESUMO

PURPOSE: To explore the association between retinal neurodegeneration and metabolic parameters in progressive dysglycemia. METHOD: A cross-sectional study was performed on 68 participants: normal glucose tolerance (n = 23), prediabetes (n = 25), and Type 2 diabetes without diabetic retinopathy (n = 20). Anthropometric assessment and laboratory sampling for HbA1c, fasting glucose, insulin, c-peptide, lipid profile, renal function, and albumin-to-creatinine ratio were conducted. Central and pericentral macular thicknesses on spectral domain optical coherence tomography were compared with systemic parameters. RESULTS: Baseline demographic characteristics were similar across all groups. Cuzick's trend test revealed progressive full-thickness macular thinning with increasing dysglycemia across all three groups (P = 0.015). The urinary albumin-to-creatinine ratio was significantly correlated with full-thickness superior (R = -0.435; P = 0.0002), inferior (R = -0.409; P = 0.0005), temporal (R = -0.429; P = 0.003), and nasal (R = -0.493; P < 0.0001) pericentral macular thinning, after post hoc Bonferroni adjustment. There was no association between macular thinning and waist circumference, body mass index, blood pressure, lipid profile, or insulin resistance. CONCLUSION: Progressive dysglycemia is associated with macular thinning before the onset of visible retinopathy and occurs alongside microalbuminuria. Retinal neurodegenerative changes may help identify those most at risk from dysglycemic end-organ damage.


Assuntos
Albuminúria/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Transtornos do Metabolismo de Glucose/diagnóstico , Estado Pré-Diabético/diagnóstico , Degeneração Retiniana/diagnóstico , Idoso , Glicemia/metabolismo , Peptídeo C/sangue , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica
16.
Sci Rep ; 12(1): 2410, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165286

RESUMO

The present study aimed to distinguish different hypertriglyceridemic waist phenotypes and relevant risks of developing fatty liver and abnormal glycometabolic profiles in overweight/obese adults. A total of 1221 Chinese adults with mean (standard deviation [SD]) age of 37 (9) years, 37.3% males and 62.7% females, body mass index (BMI) of 29.0 (4.0) kg/m2, triglyceride (TG) 2.04 (1.45) mmol/L, and waist circumference (WC) 95.8 (10.7) cm were included and classified into four phenotypes: normal TG & normal WC (N-N); normal TG & high WC (N-WC); high TG & normal WC (TG-N); high TG & high WC (TG-WC). Participants in TG-WC group had the highest BMI, WC, blood pressure (BP), insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), glycosylated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL), and fatty liver. Participants within N-WC group had a significantly higher risk of fatty liver (adjusted OR 3.50 [95% CI 2.05-5.97]), as well as TG-N (adjusted OR 2.59 [95% CI 1.61-4.16]) and TG-WC (adjusted OR 4.12 [95% CI 2.28-7.46]). The risk of elevated HOMA-IR was significantly higher in TG-N (adjusted OR 2.16 [95% CI 1.33-3.50]) and TG-WC (adjusted OR 2.04 [95% CI 1.22-3.40]). The risk of elevated HbA1c was significantly higher in the TG-WC (adjusted OR 2.79 [95% CI 1.47-5.31]). Hypertriglyceridemic waist phenotype can be a potential and cost-effective method to identify individuals with a high risk of fatty liver and glycometabolic disorders.


Assuntos
Fígado Gorduroso/etiologia , Obesidade/complicações , Sobrepeso/complicações , Triglicerídeos/sangue , Adulto , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , China , HDL-Colesterol/sangue , Estudos Transversais , Fígado Gorduroso/metabolismo , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Cintura Hipertrigliceridêmica , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/fisiopatologia , Sobrepeso/metabolismo , Sobrepeso/fisiopatologia , Fenótipo , Fatores de Risco , Circunferência da Cintura , Adulto Jovem
17.
Sci Rep ; 12(1): 2510, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35169165

RESUMO

It has not been elucidated whether incretins affect insulin clearance in type 2 diabetes (T2D). We aimed exploring possible associations between insulin clearance and endogenously secreted or exogenously administered incretins in T2D patients. Twenty T2D patients were studied (16 males/4 females, 59 ± 2 years (mean ± standard error), BMI = 31 ± 1 kg/m2, HbA1c = 7.0 ± 0.1%). Patients were treated with metformin, sitagliptin, metformin/sitagliptin combination, and placebo (randomized order). On each treatment period, oral and isoglycemic intravenous glucose infusion tests were performed (OGTT, IIGI, respectively). We also studied twelve T2D patients (9 males/3 females, 61 ± 3 years, BMI = 30 ± 1 kg/m2, HbA1c = 7.3 ± 0.4%) that underwent infusion of GLP-1(7-36)-amide, GIP, GLP-1/GIP combination, and placebo. Plasma glucose, insulin, C-peptide, and incretins were measured. Insulin clearance was assessed as insulin secretion to insulin concentration ratio. In the first study, we found OGTT/IIGI insulin clearance ratio weakly inversely related to OGTT/IIGI total GIP and intact GLP-1 (R2 = 0.13, p < 0.02). However, insulin clearance showed some differences between sitagliptin and metformin treatment (p < 0.02). In the second study we found no difference in insulin clearance following GLP-1 and/or GIP infusion (p > 0.5). Thus, our data suggest that in T2D there are no relevant incretin effects on insulin clearance. Conversely, different antidiabetic treatments may determine insulin clearance variations.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Polipeptídeo Inibidor Gástrico/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Hipoglicemiantes/administração & dosagem , Incretinas/administração & dosagem , Secreção de Insulina/efeitos dos fármacos , Metformina/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Fosfato de Sitagliptina/administração & dosagem , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada/métodos , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Teste de Tolerância a Glucose/métodos , Humanos , Hipoglicemiantes/sangue , Incretinas/sangue , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Fosfato de Sitagliptina/sangue , Resultado do Tratamento
18.
Molecules ; 27(3)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35164238

RESUMO

Natural products continue to provide inspiring moieties for the treatment of various diseases. In this regard, investigation of wild plants, which have not been previously explored, is a promising strategy for reaching medicinally useful drugs. The present study aims to investigate the antidiabetic potential of nine Amaranthaceae plants: Agathophora alopecuroides, Anabasis lachnantha, Atriplex leucoclada, Cornulaca aucheri, Halothamnus bottae, Halothamnus iraqensis, Salicornia persia, Salsola arabica, and Salsola villosa, growing in the Qassim area, the Kingdom of Saudi Arabia. The antidiabetic activity of the hydroalcoholic extracts was assessed using in vitro testing of α-glucosidase and α-amylase inhibitory effects. Among the nine tested extracts, A. alopecuroides extract (AAE) displayed potent inhibitory activity against α-glucosidase enzyme with IC50 117.9 µg/mL noting better activity than Acarbose (IC50 191.4 µg/mL). Furthermore, AAE displayed the highest α- amylase inhibitory activity among the nine tested extracts, with IC50 90.9 µg/mL. Based upon in vitro testing results, the antidiabetic activity of the two doses (100 and 200 mg/kg) of AAE was studied in normoglycemic and streptozotocin (STZ)-induced diabetic mice. The effects of the extract on body weight, food and water intakes, random blood glucose level (RBGL), fasting blood glucose level (FBGL), insulin, total cholesterol, and triglycerides levels were investigated. Results indicated that oral administration of the two doses of AAE showed a significant dose-dependent increase (p < 0.05) in the body weight and serum insulin level, as well as a significant decrease in food and water intake, RBGL, FBGL, total cholesterol, and triglyceride levels, in STZ-induced diabetic mice, compared with the diabetic control group. Meanwhile, no significant differences of both extract doses were observed in normoglycemic mice when compared with normal control animals. This study revealed a promising antidiabetic activity of the wild plant A. alopecuroides.


Assuntos
Amaranthaceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Controle Glicêmico/métodos , Hipoglicemiantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Glicemia/metabolismo , Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Insulina/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estreptozocina , Triglicerídeos/sangue
19.
Sci Rep ; 12(1): 2434, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165331

RESUMO

Emerging evidence suggests that disruption of circadian rhythmicity contributes to development of comorbid depression, cardiovascular diseases (CVD), and type 2 diabetes mellitus (T2DM). Physical exercise synchronizes the circadian system and has ameliorating effects on the depression- and anxiety-like phenotype induced by circadian disruption in mice and sand rats. We explored the beneficial effects of voluntary wheel running on daily rhythms, and the development of depression, T2DM, and CVD in a diurnal animal model, the fat sand rat (Psammomys obesus). Voluntary exercise strengthened general activity rhythms, improved memory and lowered anxiety- and depressive-like behaviors, enhanced oral glucose tolerance, and decreased plasma insulin levels and liver weight. Animals with access to a running wheel had larger heart weight and heart/body weight ratio, and thicker left ventricular wall. Our results demonstrate that exercising ameliorates pathological-like daily rhythms in activity and blood glucose levels, glucose tolerance and depressive- and anxiety-like behaviors in the sand rat model, supporting the important role of physical activity in modulating the "circadian syndrome" and circadian rhythm-related diseases. We suggest that the utilization of a diurnal rodent animal model may offer an effective way to further explore metabolic, cardiovascular, and affective-like behavioral changes related to chronodisruption and their underlying mechanisms.


Assuntos
Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/terapia , Transtornos Cronobiológicos/complicações , Transtornos Cronobiológicos/terapia , Ritmo Circadiano , Depressão/complicações , Depressão/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Terapia por Exercício/métodos , Condicionamento Físico Animal/métodos , Animais , Ansiedade/complicações , Ansiedade/fisiopatologia , Ansiedade/terapia , Glicemia/análise , Doenças Cardiovasculares/fisiopatologia , Transtornos Cronobiológicos/fisiopatologia , Depressão/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Modelos Animais de Doenças , Gerbillinae , Teste de Tolerância a Glucose , Insulina/sangue , Locomoção , Masculino , Ratos , Núcleo Supraquiasmático/fisiopatologia , Resultado do Tratamento
20.
PLoS One ; 17(2): e0263774, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35192641

RESUMO

INTRODUCTION: Fibroblast growth factor (FGF) 21 is an important regulator of glycemic control, but the association between circulating FGF21 and diabetic complications is poorly understood. Moreover, basal FGF21 secretion, especially in response to insulin dose, in patients with type 1 diabetes mellitus (T1DM), has not been well examined. Therefore, this study aimed to determine the association of circulating FGF21 levels with diabetic complications and insulin dosage in middle-aged and elderly patients with T1DM. MATERIALS AND METHODS: A total of 127 middle-aged and elderly patients with T1DM, including 68 patients with diabetic complications, and 106 non-diabetic individuals were analyzed in this cross-sectional study. Information on demographic characteristics and T1DM was extracted from their electronic medical records. Serum FGF21 levels were determined using ELISA. RESULTS: Serum FGF21 levels were significantly lower in T1DM patients (75.2 [37.4-135.1] pg/mL) than in non-diabetic participants (151.6 [92.0-224.6] pg/mL; P < 0.001). No diabetic complications were associated with serum FGF21 concentrations. Both basal and bolus insulin doses were significantly and positively correlated with serum FGF21 levels (P < 0.05). Stepwise multiple regression analysis showed that FGF21 level was associated with age and body mass index (P < 0.05), while the basal insulin dose was an independent positive predictor of serum FGF21 levels (ß = 0.197, P = 0.032). CONCLUSIONS: Circulating FGF21 levels are reduced in patients with T1DM; however, they are not associated with diabetic complications. In addition, aging, obesity, and insulin dosage are positive determinants of circulating FGF21.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Nefropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/epidemiologia , Retinopatia Diabética/epidemiologia , Fatores de Crescimento de Fibroblastos/sangue , Insulina/administração & dosagem , Adulto , Idoso , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Insulina/sangue , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA