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1.
J Cell Biol ; 221(10)2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36053215

RESUMO

Insulin levels are essential for the maintenance of glucose homeostasis, and deviations lead to pathoglycemia or diabetes. However, the metabolic mechanism controlling insulin quantity and quality is poorly understood. In pancreatic ß cells, insulin homeostasis and release are tightly governed by insulin secretory granule (ISG) trafficking, but the required regulators and mechanisms are largely unknown. Here, we identified that VAMP4 controlled the insulin levels in response to glucose challenge. VAMP4 deficiency led to increased blood insulin levels and hyperresponsiveness to glucose. In ß cells, VAMP4 is packaged into immature ISGs (iISGs) at trans-Golgi networks and subsequently resorted to clathrin-coated vesicles during granule maturation. VAMP4-positive iISGs and resorted vesicles then fuse with lysosomes facilitated by a SNARE complex consisting of VAMP4, STX7, STX8, and VTI1B, which ensures the breakdown of excess (pro)insulin and obsolete materials and thus maintenance of intracellular insulin homeostasis. Thus, VAMP4 is a key factor regulating the insulin levels and a potential target for the treatment of diabetes.


Assuntos
Insulina , Lisossomos , Proteínas R-SNARE , Vesículas Secretórias , Diabetes Mellitus , Glucose/metabolismo , Humanos , Insulina/sangue , Células Secretoras de Insulina/metabolismo , Lisossomos/metabolismo , Proteínas R-SNARE/metabolismo , Vesículas Secretórias/metabolismo , Rede trans-Golgi/metabolismo
2.
Bratisl Lek Listy ; 123(9): 618-624, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36039878

RESUMO

RESULTS: The overworld health problem, the incurable disease, the global burden on health insurers and society, and above all one of the leading causes of death - all characterize diabetes mellitus, a lifelong chronic disease that affects hundreds of millions of people around the world. The new types of biosensors bring new opportunities in the care of diabetic patients and improve current methods. The practical relevance of the recent findings is expected in medicine in next years. CONCLUSIONS: The authors summarized the modern possibilities of biosensing, their pros and cons, and their perspectives for the future. The discussion outcome from the current literature (Tab. 4, Fig. 1, Ref. 63).


Assuntos
Técnicas Biossensoriais , Glicemia , Diabetes Mellitus , Insulina , Glicemia/análise , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Humanos , Insulina/análise , Insulina/sangue
3.
Medicine (Baltimore) ; 101(34): e30200, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36042665

RESUMO

Recently, the prevalence of colorectal cancer has been increasing in Korea. Several studies have reported that adenomatous polyps, known as precancerous lesions, are associated with increased blood insulin levels. The principal objective of the present study was to examine the correlation between insulin levels and colon polyps in subjects without a history of diabetes or colorectal cancer. From January 2, 2018 to December 31, 2019, 3277 adults who visited the University Hospital Health Examination Center and underwent colonoscopy were included in this study. Insulin, glycated hemoglobin (HbA1c), and fasting blood glucose levels were measured, and past medical history, alcohol consumption, smoking, and physical activity were assessed using self-administered questionnaires. Among the 3277 subjects, the prevalence of adenomatous and nonadenomatous lesions were 22.2% and 11.5%, respectively. The mean values of insulin, HbA1c, and fasting blood glucose were significantly increased in the adenomatous and nonadenomatous polyp groups compared to the normal group. Logistic regression analysis showed that the risk of adenoma (odds ratio [OR] 1.483; 95% confidence interval [CI], 1.170-1.878) and nonadenomatous polyps (OR 1.415; 95% CI, 1.038-1.929) were increased in the high insulin level group (≥7.36 uIU/mL), and only the risk of adenoma (OR 1.312; 95% CI, 1.003-1.718) was significantly higher after adjustment for disturbance variables. This study suggests that an increase in insulin levels is a significant risk factor for colon adenoma.


Assuntos
Adenoma , Pólipos Adenomatosos , Neoplasias do Colo , Pólipos do Colo , Insulina , Adenoma/complicações , Adenoma/epidemiologia , Pólipos Adenomatosos/complicações , Adulto , Glicemia , Neoplasias do Colo/complicações , Neoplasias do Colo/epidemiologia , Pólipos do Colo/diagnóstico , Colonoscopia/efeitos adversos , Hospitais , Humanos , Insulina/sangue , Estudos Retrospectivos , Fatores de Risco
4.
Front Endocrinol (Lausanne) ; 13: 918467, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774143

RESUMO

Irisin is a myokine involved in the browning of white adipose tissue and regulation of energy expenditure, glucose homeostasis and insulin sensitivity. Debated evidence exists on the metabolic role played by irisin in children with overweight or obesity, while few information exist in children with Prader Willi Syndrome (PWS), a condition genetically prone to obesity. Here we assessed serum irisin in relation to the metabolic profile and body composition in children and adolescents with and without PWS. In 25 PWS subjects [age 6.6-17.8y; body mass index standard deviation score (BMI SDS) 2.5 ± 0.3] and 25 age, and BMI-matched controls (age 6.8-18.0y; BMI SDS, 2.8 ± 0.1) we assessed irisin levels and metabolic profile inclusive of oral glucose tolerance test (OGTT), and body composition by dual-energy X-ray absorptiometry (DXA). In PWS, we recorded lower levels of fat-free mass (FFM) (p <0.05), fasting (p<0.0001) and 2h post-OGTT insulin (p<0.05) and lower insulin resistance as expressed by homeostatic model of insulin resistance (HOMA-IR) (p<0.0001). Irisin levels were significantly lower in PWS group than in controls with common obesity (p<0.05). In univariate correlation analysis, positive associations linked irisin to insulin OGTT0 (p<0.05), insulin OGTT120 (p<0.005), HOMA-IR (p<0.05) and fasting C-peptide (p<0.05). In stepwise multivariable regression analysis, irisin levels were independently predicted by insulin OGTT120. These results suggest a link between irisin levels and insulin sensitivity in two divergent models of obesity.


Assuntos
Fibronectinas , Glucose , Obesidade , Síndrome de Prader-Willi , Adolescente , Glicemia/metabolismo , Criança , Fibronectinas/sangue , Fibronectinas/metabolismo , Glucose/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Obesidade/sangue , Síndrome de Prader-Willi/sangue , Síndrome de Prader-Willi/metabolismo
5.
Int J Mol Sci ; 23(15)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35897684

RESUMO

As a day animal with sensitivity to inflammation similar to that of humans, the sheep may highly outperform the rodent model in inflammation studies. Additionally, seasonality makes sheep an interesting model in endocrinology research. Although there are studies concerning inflammation's influence on leptin secretion and vice versa, a ewe model, with its possible 'long-day leptin resistance', is still not examined enough. The present study aimed to examine whether leptin may modulate an acute inflammation influence on plasma hormones in two photoperiodical conditions. The experiment was conducted on 48 ewes divided into four groups (control, lipopolysaccharide (LPS), leptin, LPS + leptin) during short and long days. Blood sampling started 1 hour before and continued 3 h after LPS/saline administration for further hormonal analysis. The results showed that the photoperiod is one of the main factors influencing the basal concentrations of several hormones with higher values of leptin, insulin and thyroid hormones during long days. Additionally, the acute inflammation effect on cortisol, insulin and thyroid hormones was photoperiod-dependent. The endotoxemia may also exert an influence on leptin concentration regardless of season. The effects of leptin alone on hormone blood concentrations are rather limited; however, leptin can modulate the LPS influence on insulin or thyroxine in a photoperiod-dependent way.


Assuntos
Insulina , Leptina , Fotoperíodo , Tiroxina , Animais , Feminino , Hidrocortisona , Inflamação , Insulina/sangue , Leptina/sangue , Lipopolissacarídeos , Ovinos , Tiroxina/sangue
6.
PLoS One ; 17(5): e0268086, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35639706

RESUMO

Lipocalin-2 and visfatin are proinflammatory adipokines involved in the regulation of glucose homeostasis. Their role has been described in numerous inflammatory skin diseases such as atopic dermatitis and psoriasis. Recently, an increased prevalence of metabolic abnormalities has been reported in patients with alopecia areata. The aim of the study is to determine the serum levels of lipocalin-2 and visfatin in patients with alopecia areata in comparison with healthy controls. Moreover, the serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol), high-density lipoprotein cholesterol (HDL-cholesterol), triglycerides, fasting glucose, insulin, c-peptide, and homeostasis model assessment for insulin resistance (HOMA-IR) were evaluated. Fifty-two patients with alopecia areata and 17 control subjects were enrolled in the study. The serum levels of lipocalin-2 [mean ± standard deviation, SD: 224.55 ± 53.58 ng/ml vs. 188.64 ± 44.75, p = 0.01], insulin [median (interquartile range, IQR): 6.85 (4.7-9.8) µIU/ml vs. 4.5 (3.5-6.6), p<0.05], c-peptide [median (IQR): 1.63 (1.23-2.36) ng/ml vs. 1.37 (1.1-1.58), p<0.05)], and HOMA-IR [median (IQR): 1.44 (0.98-2.15) vs. 0.92 (0.79-1.44), p<0.05) were significantly higher in patients with alopecia areata compared to the controls. The serum concentration of insulin and HOMA-IR correlated with the number of hair loss episodes (r = 0.300, p<0.05 and r = 0.322, p<0.05, respectively). Moreover, a positive correlation occurred between insulin, HOMA-IR, c-peptide and BMI (r = 0.436, p <0.05; r = 0.384, p<0.05 and r = 0.450, p<0.05, respectively). In conclusion, lipocalin-2 and insulin may serve as biomarkers for alopecia areata. Further studies are needed to evaluate the role of insulin as a prognostic factor in alopecia areata.


Assuntos
Alopecia em Áreas , Resistência à Insulina , Insulina , Lipocalina-2 , Alopecia em Áreas/diagnóstico , Biomarcadores/sangue , Peptídeo C , HDL-Colesterol , Glucose , Humanos , Insulina/sangue , Lipocalina-2/sangue , Nicotinamida Fosforribosiltransferase
7.
Front Endocrinol (Lausanne) ; 13: 840361, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35586622

RESUMO

Introduction: The known markers of insulin resistance in obese children are well studied. However, they require serial measurements and complicated calculations. The objective is to study IGFBP-1 and its relation with other known risk measures. Materials and Methods: The study included 98 New York City school students of diverse ethnic/racial backgrounds (57 males and 41 females), 11-15 years of age. Subjects were enrolled in a cross-sectional study, and anthropometric measures were collected. They underwent fasting intravenous glucose tolerance tests (IVGTT), and glucose, insulin, lipids, IGFBP-1, adiponectin and inflammatory markers were collected. Results: The subjects were stratified into 3 groups based upon the BMI Z-score. Out of all the subjects, 65.3% were in the group with a BMI Z-score <1 SDS, 16.3% subjects were in the group with a BMI Z-score of 1 to 2 SDS, and 18.4% of the subjects were in the group with a BMI Z-score of more than 2 SDS. The group with a BMI Z-score of more than 2 SDS had increased waist circumference (WC), body fat, increased fasting insulin, and triglycerides (TG). This group had decreased levels of adiponectin and HDL and low IGFBP-1 as compared to the group with BMI <1 SDS. The group with a BMI Z-score of 1 to 2 SDS had a decreased level of IGFBP-1 as compared to the group with a BMI Z-score less than 1 SDS. IGFBP-1 inversely correlated with age, WC, BMI, body fat, TG, and insulin levels. IGFBP-1 positively correlated with adiponectin and HDL levels. Conclusion: IGFBP-1 in children can identify the presence of insulin resistance in the group with BMI 1 to 2 SDS, even before the known markers of insulin resistance such as elevated triglycerides and even before decreased HDL and adiponectin levels are identified.


Assuntos
Resistência à Insulina , Obesidade Pediátrica , Adiponectina , Adolescente , Biomarcadores/sangue , Índice de Massa Corporal , Criança , Estudos Transversais , Jejum/sangue , Feminino , Humanos , Insulina/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Masculino , Obesidade Pediátrica/sangue , Triglicerídeos/sangue
8.
Clin Nutr ; 41(6): 1272-1280, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35504170

RESUMO

BACKGROUND & AIMS: Insulin and insulin-like growth factor (IGF)-1 signaling is a proposed mechanism linking dietary protein and major chronic diseases. However, it is unclear whether animal and plant proteins are associated with biomarkers of insulin and IGF axis. METHODS: We analyzed a total of 14,709 participants from Nurses' Health Study and Health Professionals Follow-up Study who had provided a blood sample. Detailed dietary information was assessed using validated food frequency questionnaires. We assessed C-peptide, insulin, IGF-1, and IGF binding proteins (BP). Multivariable-adjusted linear regressions were used to examine associations of animal and plant protein intake with biomarkers after adjusting for confounders. RESULTS: The medians (5th-95th percentiles) of animal and plant protein intake (% of total energy) were 13% (8-19%) and 5% (4-7%), respectively. Compared to participants in the lowest quintile, those in the highest quintile of animal protein had 4.8% (95% CI: 1.9, 7.9; P-trend<0.001) higher concentration of IGF-1 and -7.2% (95% CI: -14.8, 1.1; P for trend = 0.03) and -11.8% (95% CI: -20.6, -1.9; P-trend<0.001) lower concentration of IGFBP-1 and IGFBP-2, respectively, after adjustment for major lifestyle factors and diet quality. In contrast, no association was observed between animal protein intake and C-peptide, insulin and IGFBP-3. The associations were restricted to participants with at least one unhealthy lifestyle risk factor (i.e., overweight/obese, physical inactivity, smoking, and heavy alcohol intake). Plant protein tended to be strongly associated with numerous biomarkers in age-adjusted analyses but these became largely attenuated or non-significant in multivariable adjustment. Plant protein intake remained positively associated with IGF-1 (P-trend = 0.002) and possibly IGFBP-1 (P-trend = 0.02) after multivariable adjustment. Substitution of plant protein with animal protein sources was associated with lower IGFBP-1. In additional analysis, IGF-1 and IGFBPs were estimated to mediate approximately 5-20% of the association between animal protein and type 2 diabetes. CONCLUSIONS: Higher animal protein intake was associated with higher IGF-1 and lower IGFBP-1 and IGFBP-2, whereas higher plant protein intake was associated with higher IGF-1 and IGFBP-1.


Assuntos
Diabetes Mellitus Tipo 2 , Proteínas na Dieta , Proteínas Animais da Dieta , Animais , Biomarcadores/sangue , Peptídeo C/sangue , Diabetes Mellitus Tipo 2/sangue , Proteínas na Dieta/sangue , Seguimentos , Humanos , Insulina/sangue , Insulina/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Proteínas de Vegetais Comestíveis
9.
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 , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/metabolismo , Extratos Vegetais/uso terapêutico
10.
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
11.
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 , Redução de Peso/efeitos dos fármacos , Adulto Jovem
12.
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 , Redução 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
13.
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
14.
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
15.
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
16.
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
17.
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
18.
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
19.
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
20.
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 , 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
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