Effects of maternal high-fat diet and exercise intervention on insulin sensitivity and the hypothalamic arcuate nucleus in male offspring mice / 中国组织工程研究

BACKGROUND:In the offspring of obese mothers,some metabolic genes are"silent"under certain environmental influences.These"silent"genes may be"awakened"under the acquired environment and then cause metabolic regulation disorders. OBJECTIVE:In the case of offspring with different diets,to explore the metabolic genetic effects of long-term high-fat and exercise intervention in female mice. METHODS:Seventy 3-week-old female C57BL/6 mice were divided into high-fat diet(HFD)and high-at exercise groups(high-fat diet+exercise,HFD-Ex),and they gave birth naturally after 16 weeks of intervention.After 4-week lactation,16 male offspring mice from each group were randomly selected.Totally 32 offspring mice were randomly divided into 4 subgroups and given high-fat diet or standard chow diet for 6 weeks:HFD-HFD,HFD-Ex-HFD,HFD-standard chow diet,and HFD-Ex-standard chow diet.The offspring mice were subjected to glucose tolerance test and insulin tolerance test in the 10th week,followed by body composition analysis and sacrifice.Western blot was used to determine the level of p-Akt in the liver.Immunofluorescence of the hypothalamic arcuate nucleus was used to analyze the expression of neuropeptide Y and pro-opiomelanocortion. RESULTS AND CONCLUSION:Under the high-fat diet,compared with the HFD group,the offspring of the HFD-Ex group had significantly improvements in glucose metabolism,body mass,and body composition(P＜0.05).Under the standard chow diet,compared with the HFD group,the expression of neuropeptide Y in the hypothalamic arcuate nucleus of the HFD-Ex group was significantly decreased(P＜0.05),and the expression of pro-opiomelanocortion was significantly up-regulated(P＜0.05).In the case of insulin(-),the expression of phosphorylated Akt(Ser473)protein in the liver showed no significant difference between the two groups,but in the case of insulin(+),there was a significant difference between the two groups(P＜0.05).In the high-fat diet mode,the metabolic protection effect of the maternal long-term exercise may gradually weaken with the prolongation of the offspring's high-fat exposure;in the standard chow diet mode,the maternal long-term exercise can improve the central regulation of energy metabolism and insulin sensitivity of the male offspring.

Sleep quality and diabetes associated factors, effect and interventions

Getting sleep is incredibly important for maintaining health and well-being, especially for individuals who have diabetes. Poor sleep quality can have an effect on how our bodies process glucose and utilize insulin potentially resulting in diabetes related issues and complications. Additionally, we explore interventions that have the potential to improve both sleep quality and overall diabetes outcomes. Through this review it is indicated that inadequate sleep quality can influence glucose control, increase the risk of complications associated with diabetes and reduce quality of life. Furthermore, we've identified interventions that show promise in improving both sleep quality and overall outcomes for individuals with diabetes. These interventions include implementing lifestyle changes, making modifications utilizing behavioral therapies and incorporating device-based strategies. We suggest that future studies use experimental designs and objective measures of sleep quality and glucose metabolism and include diverse samples of different types of diabetes.

Breaking up sedentary time to improve glucose control in a population at risk for developing type 2 diabetes (BURST2D study): a randomized controlled trial

Background: To compare the acute and chronic effects of frequent, short physical activity (PA) bouts spread throughout the day to a time-matched intervention consisting in a single continuous daily bout of PA on glucose control and potential underlying mechanisms in adults at risk of developing type 2 diabetes (T2D). Methods: BURST2D is a single-center, parallel-group, randomized controlled trial, in which sedentary adults with overweight/obesity and pre-diabetes (18-45 y, BMI: 25-40 kg/m2, fasting glucose: 100-125 mg/dL or 2h glucose: 140-199 mg/dL or HbA1c: 5.7-6.4%) will be randomly assigned to one of two 3-month PA interventions: BREAK, nine bouts of 5-min brisk walking performed every hour for nine consecutive hours (45-min/d total), 5 days/wk; ONE, one continuous 45-min bout of brisk walking, 5 days/wk. Primary outcomes will be daily glycemic mean and variability, fasting glucose and HbA1c, postprandial plasma glucose and insulin, glucose kinetics, and content of skeletal muscle proteins related to insulin signaling and glucose uptake. Secondary outcomes will be whole-body insulin sensitivity, 24-h total substrate oxidation, postprandial triglycerides, daily PA and sedentary behavior (SB) patterns, knowledge and attitude towards PA and SB, barriers and facilitators to intervention compliance, self-perceived appetite, mood, and sleep. Outcomes will be assessed at baseline and after one month and/or three months of intervention. Conclusions: This study will establish the acute and chronic effects of breaking up SB, independent of increases in PA, on glucose control and underlying mechanisms in adults with pre-diabetes. Results will advance the science of T2D prevention. Trial registration: This study is registered with the ClinicalTrials.gov, registry number NTC05041491

Altered circulating adipokines and heart rate variability: A biomarker for autonomic imbalance in obese individuals

Background: Evidences indicate altered circulating adipokine levels in obesity could increase the risk for cardiovascular disease (CVD). Hence, it is crucial to determine cardiovascular health by assessing heart rate variability (HRV) and its association with circulating adipokines. Aim and Objectives: The aim of the study was to assess the adipokines level and its association with HRV in obese population. Materials and Methods: A cross-sectional comparative study was conducted on 45 obese (body mass index [BMI] > 25–29.9 kg/m2) and 45 non-obese (BMI: 18.5–22.9 kg/m2) age-gender-matched participants. Lead-II electrocardiogram was recorded and HRV parameters were obtained. Biochemical parameters, that is, fasting blood glucose, fasting insulin, HOMA-IR, lipid profile, leptin, and adiponectin levels were estimated. Group comparisons were done by independent student’s t-test, whereas the association between the parameters was done by Pearson’s correlation using SPSS 20v. P < 0.05 was considered statistically significant. Results: There was a significant increase in low frequency: high frequency (LF: HF) ratio (<0.001), fasting insulin (<0.001), HOMA-IR (<0.001), leptin (<0.001), Leptin-Adiponectin ratio (L/A ratio) (<0.001), total cholesterol (<0.001), triglycerides (<0.001), and low-density lipoproteins (<0.001), whereas significant decrease in total power (TP) of HRV (TP) (<0.001), adiponectin (<0.001), and high-density lipoproteins. A significant positive correlation between leptin, L/A ratio with LF: HF ratio (r = 0.793, P < 0.001) and a negative correlation with TP (–0.463, P < 0.001) was observed. Conclusion: Altered adipokines and its association with HRV in obese individuals could be an indicator of CVD. Hence, the current study suggests that the L/A ratio might be considered as a biomarker for cardiovascular health in obese individuals.

CD36 gene deletion reduces muscle insulin sensitivity in mice by up-regulating PTP1B expression / 南方医科大学学报

OBJECTIVE@#To investigate the effect CD36 deficiency on muscle insulin signaling in mice fed a normal-fat diet and explore the possible mechanism.@*METHODS@#Wild-type (WT) mice and systemic CD36 knockout (CD36-/-) mice with normal feeding for 14 weeks (n=12) were subjected to insulin tolerance test (ITT) after intraperitoneal injection with insulin (1 U/kg). Real-time PCR was used to detect the mRNA expressions of insulin receptor (IR), insulin receptor substrate 1/2 (IRS1/2) and protein tyrosine phosphatase 1B (PTP1B), and Western blotting was performed to detect the protein expressions of AKT, IR, IRS1/2 and PTP1B in the muscle tissues of the mice. Tyrosine phosphorylation of IR and IRS1 and histone acetylation of PTP1B promoter in muscle tissues were detected using co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP), respectively.@*RESULTS@#CD36-/- mice showed significantly lowered insulin sensitivity with obviously decreased area under the insulin tolerance curve in comparison with the WT mice (P < 0.05). CD36-/- mice also had significantly higher serum insulin concentration and HOMA-IR than WT mice (P < 0.05). Western blotting showed that the p-AKT/AKT ratio in the muscle tissues was significantly decreased in CD36-/- mice as compared with the WT mice (P < 0.01). No significant differences were found in mRNA and protein levels of IR, IRS1 and IRS2 in the muscle tissues between WT and CD36-/- mice (P>0.05). In the muscle tissue of CD36-/- mice, tyrosine phosphorylation levels of IR and IRS1 were significantly decreased (P < 0.05), and the mRNA and protein levels of PTP1B (P < 0.05) and histone acetylation level of PTP1B promoters (P < 0.01) were significantly increased as compared with those in the WT mice. Intraperitoneal injection of claramine, a PTP1B inhibitor, effectively improved the impairment of insulin sensitivity in CD36-/- mice.@*CONCLUSION@#CD36 is essential for maintaining muscle insulin sensitivity under physiological conditions, and CD36 gene deletion in mice causes impaired insulin sensitivity by up-regulating muscle PTP1B expression, which results in detyrosine phosphorylation of IR and IRS1.

Effect of free fatty acids on insulin secretion, insulin sensitivity and incretin effect - a narrative review

ABSTRACT Deleterious effects of free fatty acids, FFAs, on insulin sensitivity are observed in vivo studies in humans. Mechanisms include impaired insulin signaling, oxidative stress, inflammation, and mitochondrial dysfunction, but the effects on insulin secretion are less well known. Our aim was to review the relationship of increased FFAs with insulin resistance, secretion and mainly with the incretin effect in humans. Narrative review. Increased endogenous or administered FFAs induce insulin resistance. FFAs effects on insulin secretion are debatable; inhibition and stimulation have been reported, depending on the type and duration of lipids exposition and the study subjects. Chronically elevated FFAs seem to decrease insulin biosynthesis, glucose-stimulated insulin secretion and β-cell glucose sensitivity. Lipids infusion decreases the response to incretins with unchanged incretin levels in volunteers with normal glucose tolerance. In contrast, FFAs reduction by acipimox did not restore the incretin effect in type-2 diabetes, probably due to the dysfunctional β-cell. Possible mechanisms of FFAs excess on incretin effect include reduction of the expression and levels of GLP-1 (glucagon like peptide-1) receptor, reduction of connexin-36 expression thus the coordinated secretory activity in response to GLP-1, and GIP (glucose-dependent insulinotropic polypeptide) receptors downregulation in islets cells. Increased circulating FFAs impair insulin sensitivity. Effects on insulin secretion are complex and controversial. Deleterious effects on the incretin-induced potentiation of insulin secretion were reported. More investigation is needed to better understand the extent and mechanisms of β-cell impairment and insulin resistance induced by increased FFAs and how to prevent them.

Correlations between C-peptide insulin resistance index, very low density lipoprotein-cholesterol and atherogenic index in type 2 diabetic patients / 中国医师杂志

Objective:To investigate the correlation between multiple parameters of islet function evaluation and atherogenic index (AIP) in patients with type 2 diabetes mellitus (T2DM).Methods:A cross-sectional study was conducted to observe 216 T2DM patients hospitalized in Tianjin Medical University Chu Hsien-I Memorial Hospital in 2019. They were divided into non atherogenic phenotype group (N Group, AIP<0.06) and atherogenic phenotype group (A group, AIP≥0.06) with AIP=0.06 as the cut-off point. The general clinical indexes and evaluation indexes of oral glucose tolerance test (OGTT), such as insulin action index (IAI), quantitative insulin sensitivity check index (QUICKI), homeostasis model of insulin resistance index (HOMA-IR), homeostasis model assessment-β (HOMA-β), C peptide insulin resistance index (HOMA IR-CP) and C peptide islet function index suitable to diabetes patients (HOMA islet-CP DM) were compared between two groups. Pearson correlation analysis and multiple stepwise regression analysis were performed.Results:Compared with the N group, the very low density lipoprotein-cholesterol (VLDL-C), ln (HOMA IR-CP) and ln (HOMA islet-CP DM) in A group were higher ( P<0.01), while ln (QUICKI) was lower ( P<0.05), with statistical significance. AIP was positively correlated with VLDL-C ( r=0.765), ln (HOMA-IR) ( r=0.257), ln (HOMA-β) ( r=0.189), ln (HOMA IR-CP) ( r=0.418) and ln (HOMA islet-CP DM) ( r=0.377, P<0.01), and negatively correlated with IAI ( r=-0.145, P<0.05) and ln (QUICKI) ( r=-0.254, P<0.01). Multiple stepwise regression analysis showed that VLDL-C and ln (HOMA IR-CP) were independent influencing factors of AIP in type 2 diabetic patients ( P<0.01) . Conclusions:AIP is positively correlated with insulin resistance and negatively correlated with insulin sensitivity. VLDL-C and HOMA IR-CP are independent predictors of AIP.

Study on effect of gypenosides on insulin sensitivity of rats with diabetes mellitus via regulating NF-κB signaling pathway / 中国中药杂志

This study focused on the ameliorative effects of gypenosides(GPS) on insulin sensitivity and inflammatory factors in rats with type 2 diabetes mellitus(T2 DM) and explored their possible molecular mechanisms. After the successful establishment of T2 DM model, diabetic rats were randomly divided into four groups, including model group, GPS groups(200, 100 mg·kg~(-1)) and metformin group(100 mg·kg~(-1)), with healthy rats serving as the control. After 6-week intragastric administration, fasting blood glucose(FBG) and oral glucose tolerance were examined. The levels of insulin, C-peptide, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) and C-reactive protein(CRP) in serum were examined. Then the homeostasis model assessment of insulin resistance(HOMA-IR) and insulin sensitivity index(ISI) were calculated. The protein expression levels of phosphorylated insulin receptor substrate-1(p-IRS-1) and phosphorylated protein kinase B(p-Akt) in skeletal muscle were measured by Western blot, as well as those of phosphorylated inhibitor of nuclear factor-κB(NF-κB) kinase β(p-IKKβ), phosphorylated alpha inhibitor of NF-κB(p-IκBα) and phosphorylated p65 subunit of NF-κB(p-p65) in adipose tissue. The relative expression levels of glucose transporter 4(GLUT4) mRNA in skeletal muscle and NF-κB mRNA in adipose tissue were measured by qRT-PCR, and the morphological changes of pancreatic tissue were observed. Compared with the model group, the GPS groups witnessed significant decrease in FBG, marked amelioration of impaired oral glucose tolerance and significant increase in ISI. Further, the high-dose GPS group saw significantly reduced HOMA-IR, TNF-α, IL-1β and CRP, significantly increased expression levels of p-IRS-1(Tyr), p-Akt and GLUT4, and markedly inhibited p-IRS-1(Ser), p-IKKβ, p-IκBα, p-p65 and NF-κB. The concentration of CRP and the expression levels of p-IRS-1(Ser), p-IKKβ, p-IκBα and NF-κB were remarkably reduced in the low-dose GPS group. However, GPS was found less effective in the regulation of serum insulin, C-peptide and IL-6 levels and the alleviation of pancreatic islet injury. The results indicated that GPS can reduce FBG and improve insulin sensitivity in diabetic rats possibly by regulating the NF-κB signaling pathway, inhibiting inflammation, and thereby regulating the expression of key proteins in the insulin signaling pathway.

Tres versiones del "Ogtt Squeezer", un programa para evaluar de un vistazo la información metabólica de la curva de tolerancia a la glucosa / Three versions of the "Ogtt Squeezer", a program to evaluate ataglance the metabolic information of the oral glucose tolerance test

El diagnóstico clínico de resistencia insulínica (RI) es difícil, ya que el Clamp no es aplicable a la clínica. El así llamado "síndrome metabólico", un predictor clínico de la RI, no identifica alrededor de la mitad de los sujetos afectados. Previamente, definimos adecuadamente (Análisis ROC) los niveles de corte diagnóstico de los siguientes predictores bioquímicos: HOMA1, HOMA2, QUICKI e ISI-Composite, a través de analizar datos de 90 sujetos (53 no resistentes y 37 resistentes) que tenían una medición directa de su resistencia insulínica (Test de supresión pancreática, TSP, Test de Reaven) y también, una curva de tolerancia a la glucosa oral (CTG). Los puntos de corte obtenidos exhibieron un mucho mejor desempeño diagnóstico comparados con los puntos de corte convencionales. También encontramos un predictor nuevo, simple, económico y eficiente, el I0*G60. Definimos la "normalidad metabólica" de la CTG usando las medianas de los valores de varios parámetros en 312 sujetos con un G120 dentro de los 2 primeros terciles del grupo de normo-tolerantes a la glucosa (NGT, n=468; G120: 51-110 mg/dL, los con mejor función beta insular). A las medianas de la función beta insular y de la sensibilidad insulínica se les asignó un valor de un 100%. Se calculó el % relativo de función beta insular (%RFBI) y el % relativo de sensibilidad insulínica (%RSI) del resto de la cohorte (n=573) contra estos valores de referencia. El "OGTT Squeezer" se escribió en Excel. Las glicemias y las insulinemias de la CTG fueron las entradas del programa. Las salidas fueron: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictores) y el índice insulinogénico, el índice de disposición, %RFBI y %RSI (parámetros). El programa también caracterizó la tolerancia glucídica de acuerdo a los criterios de la ADA 2003. El formato final del programa, HTML 5, facilita su uso. Desarrollamos tres versiones del programa: completa, abreviada y mínima.

Clinically, diagnosing insulin resistance (IR) is difficult since the Clamp is not applicable to clinical work. The so-called "Metabolic Syndrome", a clinical surrogate of IR, fails to identify around 50% of affected subjects. Previously, we properly defined (ROC Analysis) the diagnostic cut-offs of the following biochemical predictors: HOMA1, HOMA2, QUICKI, and ISI-Composite by analyzing data from 90 subjects (53 non-insulin-resistant and 37 insulin-resistant subjects) who had a direct measurement of insulin resistance (Pancreatic Suppression Test, PST, Reaven's Test), and also, an Oral Glucose Tolerance Test (OGTT). The resulting cut-offs exhibited much better performances compared with the conventional cut-offs. We also found a new, simple, inexpensive and efficient predictor, the I0*G60. We chose to define the "metabolic normalcy" of the OGTT by using the median values of several parameters in 312 NGT subjects with a G120 in the first 2 tertiles of the NGT group (n=468; G120: 51-110 mg/dL, those with the best beta-cell function). The median values of both Beta-Cell Function and Insulin Sensitivity of these subjects were assigned a 100% value. Both % Relative Beta-Cell Function (%RBCF) and % Relative Insulin Sensitivity (%RIS) of everyone else in the cohort (n=573) was calculated against these reference values. The "OGTT Squeezer" was written in Excel. The OGTT's glucose and insulin values served as the inputs of the program. The outputs were: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictors), and Insulinogenic Index, Disposition Index, %RBCF, and %RIS (parameters). Moreover, the program characterized the OGTT according to the ADA 2003 criteria. The HTML 5 format of the program facilitates its use. We developed 3 versions of the program: complete, abbreviated, and minimal versions.

Is There An Advantage of Using Dingkun Pill () alone or in Combination with Diane-35 for Management of Polycystic Ovary Syndrome? A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the effects of Chinese medicine Dingkun Pill () alone or in combination with Diane-35 on patients with polycystic ovary syndrome (PCOS).@*METHODS@#This is a prospective randomized controlled trial conducted at Peking Union Medical College Hospital Beijing, China, from December 2016 to September 2017. Totally 117 PCOS patients were randomly assigned to the Dingkun Pill group (38 cases), Diane-35 group (40 cases), or combined group (39 cases). Patients in the Dingkun Pill group or Diane-35 group took daily 7 g of oral Dingkun Pill or 1 tablet of oral Diane-35, respectively, for 21 consecutive days followed by 7 drug-free days. And the combined group received a combination of Dingkun Pill and Diane-35. The treatment course was 3 months. Fasting plasma glucose and insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), free fatty acids (FFA) and sex hormones were analyzed, quantitative insulin sensitivity check index (QUICKI) was calculated, and menstruation and acne scores were recorded at baseline and after 3-month treatment.@*RESULTS@#Compared with before treatment, QUICKI decreased significantly in the Dingkun Pill and combined groups after 3-month treatment (P0.05).@*CONCLUSIONS@#Dingkun Pill showed better effects than Diane-35 in improving insulin sensitivity, lowering TC and FFA. Diane-35 was more efficient in regulating menstruation and lowering androgen than Dingkun Pill. Combination of Dingkun Pill and Diane-35 may be a better choice to regulate menstruation, lower androgens while improve glucose metabolism in PCOS patients. (Registered on ClinicalTrials.gov, registration No. NCT03264638).

Insulin resistance is associated with Sfrp5 in obstructive sleep apnea / Resistência à insulina está associada à Sfrp5 na apneia obstrutiva do sono

Abstract Introduction: Obstructive sleep apnea, a common disease, is usually complicated by insulin resistance and type 2 diabetes mellitus. Adipokine is considered to play an important role in the development of insulin resistance and type 2 diabetes mellitus in obstructive sleep apnea. Objective: To assess whether secreted frizzled-related protein 5, a new adipokine, is involved in untreated obstructive sleep apnea patients. Methods: Seventy-six subjects with obstructive sleep apnea and thirty-three control subjects without obstructive sleep apnea were recruited and matched in terms of body mass index and age. The fasting secreted frizzled-related protein 5 plasma concentration was tested using ELISA. In addition, the correlation between secreted frizzled-related protein 5 and the homeostasis model assessment of insulin resistance was obtained. Multiple linear regression analysis models with stepwise selection were performed to determine the independent associations between various factors and secreted frizzled-related protein 5. Results: Plasma secreted frizzled-related protein 5 levels were significantly lower in the obstructive sleep apnea group than in the control group (obstructive sleep apnea group: 28.44 ± 13.25 ng/L; control group: 34.16 ± 13.51 ng/L; p = 0.023). In addition, secreted frizzled-related protein 5 was negatively correlated with homeostasis model assessment of insulin resistance but positively correlated with the mean and lowest oxygen saturation with or without adjusting for age, gender, body mass index, neck circumference, waist circumference and waist-to-hip ratio. The multiple linear regression analysis showed there was an independent negative association between secreted frizzled-related protein 5 and homeostasis model assessment of insulin resistance. Conclusion: Secreted frizzled-related protein 5 was involved in obstructive sleep apnea and the decrease in secreted frizzled-related protein 5 was directly proportional to the severity of obstructive sleep apnea. There was an independent negative correlation between homeostasis model assessment of insulin resistance and secreted frizzled-related protein 5 in the obstructive sleep apnea group. Secreted frizzled-related protein 5 might be a therapeutic target for insulin resistance in obstructive sleep apnea.

Resumo Introdução: A apneia obstrutiva do sono, uma doença comum, é geralmente complicada com resistência à insulina e diabetes melito tipo 2. Acredita-se que a adipocina possa ter um papel importante no desenvolvimento de resistência à insulina e diabetes melito tipo 2 na apneia obstrutiva do sono. Objetivo: Avaliar se a proteína secretada relacionada ao receptor frizzled-5, uma nova adipocina, está envolvida em pacientes com apneia obstrutiva do sono não tratada. Método: Foram recrutados 76 indivíduos com apneia obstrutiva do sono e 33 indivíduos controle sem apneia obstrutiva do sono e pareados em relação a índice de massa corporal e idade. A concentração plasmática de proteína secretada relacionada ao receptor frizzled-5 foi testada em jejum com o teste Elisa. Além disso, obteve-se correlação entre a proteína secretada relacionada ao receptor frizzled-5 e o modelo de avaliação da homeostase de resistência à insulina. Modelos de análise de regressão linear múltipla com seleção stepwise foram feitos para determinar as associações independentes entre vários fatores e a proteína secretada relacionada ao receptor frizzled-5. Resultados: Os níveis plasmáticos de proteína secretada relacionada ao receptor frizzled-5 foram significativamente menores no grupo com apneia obstrutiva do sono do que no grupo controle (grupo com apneia obstrutiva do sono: 28,44 ± 13,25 ng/L; grupo controle: 34,16 ± 13,51 ng/L; p = 0,023). Além disso, a proteína secretada relacionada ao receptor frizzled-5 foi correlacionada negativamente com o modelo de avaliação da homeostase de resistência à insulina, mas se correlacionou positivamente com a média e a saturação mínima de oxigênio com ou sem ajuste para idade, gênero, índice de massa corporal, circunferência do pescoço, circunferência da cintura e relação cintura-quadril. A análise de regressão linear múltipla mostrou que houve uma associação negativa independente entre a proteína secretada relacionada ao receptor frizzled-5 e o modelo de avaliação da homeostase de resistência à insulina. Conclusões: A proteína secretada relacionada ao receptor frizzled-5 esteve envolvida na apneia obstrutiva do sono e sua diminuição foi diretamente proporcional à gravidade da apneia obstrutiva do sono. Houve uma correlação negativa independente entre o modelo de avaliação da homeostase de resistência à insulina e a proteína secretada relacionada ao receptor frizzled-5 no grupo da apneia obstrutiva do sono. A proteína secretada relacionada ao receptor frizzled-5 pode ser um alvo terapêutico para a resistência à insulina na apneia obstrutiva do sono.

Insulin signaling in the whole spectrum of GH deficiency

ABSTRACT GH is one of the insulin counterregulatory hormones which acts in the opposite way to insulin, increasing the glucose production by the liver and kidneys and decreasing glucose uptake from peripheral tissues, thus being a hyperglycemic hormone. When in excess, as in acromegaly, it induces glucose intolerance and diabetes. As expected, patients with GH deficiency (GHD) have hypoglycemia, especially in early childhood, but as GH is also a lipolytic hormone, these patients are becoming obese with higher percentages of body fat. Although obesity in general is directly related to insulin resistance, in patients with GH secretion disorders this relationship may be altered. In acromegaly there is a decrease in fat mass with worsening insulin sensitivity and mice with isolated GHD are characterized by greater insulin sensitivity despite excess fat mass. In humans with GHD, body composition shows increased body fat and decreased free fat mass, but the results regarding insulin sensitivity are still controversial in these patients. These discrepant results regarding insulin sensitivity in patients with GHD suggest the existence of other variables influencing these results. In the present review, we will try to follow the path of the different researches conducted on this subject, both in animal and human models, with the goal of understanding the current knowledge of insulin sensitivity across the spectrum of GHD. Arch Endocrinol Metab. 2019;63(6):582-91

Effect of losartan and irbesartan on blood pressure and ISI in female hypertension patients complicated with hyperuricemia / 中国基层医药

Objective To compare the effects of losartan and irbesartan on blood pressure,blood uric acid,insulin sensitivity and insulin resistance in female hypertensive patients complicated with hyperuricemia.Methods From August 2015 to December 2017,100 females of hypertension complicated with hyperuricemia who hospitalized in the Third People's Hospital of Ningxia were enrolled in the study.All the patients were divided into two groups according to the random digital table,with 50 cases in each group.The observation group was treated with losartan,and the control group was treated with irbesartan for 8 weeks.The total effective rate and adverse reactions were compared between the two groups.Also the changes of blood pressure,serum uric acid,fasting glucose (FBG),fasting insulin (FINS),high sensitivity C-reactive protein (hs-CRP),insulin sensitivity index (ISI) and insulin resistance index (HOMA-IR) were compared between the two groups after treatment.Results There was no statistically significant difference in the total effective rate between the two groups [92.0％ (46/50) vs.90.0％ (45/50)] (P ＞ 0.05).Before treatment,there were no statistically significant differences in blood pressure,serum uric acid,FBG,FINS,hs-CRP,ISI and HOMA-IR between the two groups (all P ＞ 0.05).After treatment,the systolic blood pressure and diastolic blood pressure in the two groups were (133.09 ± 10.11) mmHg vs.(131.54 ± 11.01) mmHg and (82.76 ± 6.23) mmHg vs.(83.75 ± 6.88) mmHg,which were lower than those before treatment (observation group:t =19.742,10.606,control group:t =18.925,-9.956,all P ＜ 0.05).But there were no statistically significant differences between the two groups (all P ＞ 0.05).After treatment,the serum uric acid in the observation group was lower than that in the control group [(387.21 ± 25.56) μmol/L vs.(429.67 ± 27.44) μmol/L] (t =8.006,P ＜ 0.05).The hs-CRP,FINS,HOMA-IR,ISI in the observation group were (4.92 ± 1.02) rmg/L,(15.92 ± 3.01) mU/L,(1.71 ± 0.24),(1.047 ± 0.095),which in the control group were (4.54 ± 1.00) mg/L,(17.23 ± 3.20) mU/L,(1.65 ± 0.27),(1.140 ± 0.083).After treatment,the hs-CRP,FINS,HOMA-IR in the two groups were decreased (all P ＜ 0.05),while ISI was increased (P ＜ 0.05).Furthermore,the improvement of FINS,ISI and HOMA-IR in the observation group was better than those in the control group (t =2.109,-5.213,3.191,all P ＜ 0.05).Conclusion Both losartan and irbesartan can improve clinical symptoms,lower blood pressure and improve insulin resistance in female hypertension patients complicated with hyperuricemia,and losartan is more effective than irbesartan.

Regulation of microbiota-GLP1 axis by sennoside A in diet-induced obese mice

Sennoside A (SA) is a bioactive component of Chinese herbal medicines with an activity of irritant laxative, which is often used in the treatment of constipation and obesity. However, its activity remains unknown in the regulation of insulin sensitivity. In this study, the impact of SA on insulin sensitivity was tested in high fat diet (HFD)-induced obese mice through dietary supplementation. At a dosage of 30 mg/kg/day, SA improved insulin sensitivity in the mice after 8-week treatment as indicated by HOMA-IR (homeostatic model assessment for insulin resistance) and glucose tolerance test (GTT). SA restored plasma level of glucagon-like peptide 1 (GLP1) by 90% and mRNA expression of by 80% in the large intestine of HFD mice. In the mechanism, SA restored the gut microbiota profile, short chain fatty acids (SCFAs), and mucosal structure in the colon. A mitochondrial stress was observed in the enterocytes of HFD mice with ATP elevation, structural damage, and complex dysfunction. The mitochondrial response was induced in enterocytes by the dietary fat as the same responses were induced by palmitic acid in the cell culture. The mitochondrial response was inhibited in HFD mice by SA treatment. These data suggest that SA may restore the function of microbiota-GLP1 axis to improve glucose metabolism in the obese mice.

Expression and Function of Zinc-α2-Glycoprotein / 神经科学通报·英文版

Zinc-α2-glycoprotein (ZAG), encoded by the AZGP1 gene, is a major histocompatibility complex I molecule and a lipid-mobilizing factor. ZAG has been demonstrated to promote lipid metabolism and glucose utilization, and to regulate insulin sensitivity. Apart from adipose tissue, skeletal muscle, liver, and kidney, ZAG also occurs in brain tissue, but its distribution in brain is debatable. Only a few studies have investigated ZAG in the brain. It has been found in the brains of patients with Krabbe disease and epilepsy, and in the cerebrospinal fluid of patients with Alzheimer disease, frontotemporal lobe dementia, and amyotrophic lateral sclerosis. Both ZAG protein and AZGP1 mRNA are decreased in epilepsy patients and animal models, while overexpression of ZAG suppresses seizure and epileptic discharges in animal models of epilepsy, but knowledge of the specific mechanism of ZAG in epilepsy is limited. In this review, we summarize the known roles and molecular mechanisms of ZAG in lipid metabolism and glucose metabolism, and in the regulation of insulin sensitivity, and discuss the possible mechanisms by which it suppresses epilepsy.

Characteristic analysis of insulin secretion and sensitivity in pre-diabetes populations under new diagnostic criteria / 上海交通大学学报（医学版）

Objective: To investigate the characteristics of insulin secretion function and sensitivity and blood glucose disposition capacity in the prediabetes populations. Methods: A total of 1 317 subjects were enrolled in this study, including 382 with normal glucose tolerance (NGT) and 935 with pre-diabetes. All pre-diabetes populations were divided into seven subgroups according to the cut-off points of 2010 American Diabetes Association standards. Homeostasis model assessment (HOMA) was used to access baseline insulin secretion (HOMA-β) and insulin sensitivity (HOMA-IR). Insulin secretion and sensitivity after glucose load were evaluated by area under curve (AUC) for insulin/AUC for glucose (AUCINS120/AUCGLU120) and insulin sensitivity index (ISI) calculated from Cederholm formula, respectively. Disposition index (DI) was used to reflect blood glucose disposition capacity. Results: The most common type of pre-diabetes was impaired fasting glucose (IFG) combined with impaired glucose tolerance (IGT) and glycated hemoglobin A1c (HbA1c ) 5.7%-6.4%, followed by isolated IGT, while the proportion of isolated IFG was the lowest. The insulin sensitivity of isolated HbA1c 5.7%-6.4% group was better than that of isolated IFG group, isolated IGT group, and IFG combined with IGT group (P<0.05). And its β-cell function was similar with the other subgroups. The DI value of isolated HbA1c 5.7%-6.4% group was about 1.5 times of that of isolated IGT group and IFG combined with IGT group (P=0.000), which was similar with isolated IFG group. The function of β cell or insulin sensitivity in the pre-diabetes subjects with HbA1c 5.7%-6.4% was further damaged compared with the pre-diabetes people whose HbA1c were lower than 5.7%. Conclusion: Different types of pre-diabetes are significantly heterogeneous under new diagnostic criteria, and further prospective studies with a larger sample size are needed to clarify whether HbA1c 5.7%-6.4% is suitable as a diagnostic criteria for pre-diabetes in Chinese population.

Beneficial effects of anthocyanins against diabetes mellitus associated consequences-A mini review

Anthocyanins (ACN) are water-soluble pigments, belonging to flavonoids, and are present in almost all fruits, and vegetables at varying concentration. About 635 ACN were distinguished based on the position and number of methoxyl and hydroxyl moieties in the basic structure of ACN. Pelargonidin, cyanidin, delphinidin, malvidin, peonidin, and petunidin are extensively studied anthocyanidins. The absorption, bioavailability, metabolism, pharmacokinetics, molecular mechanism, and analytical techniques of several phytochemicals were described. The biological benefits (antidiabetic, anti-neuro-disorder, anti-cardiovascular diseases, antigastrointestinal diseases, and disorders) of flavonoids and ACN have been reported. Several in vitro, and in vivo reports demonstrated that ACN-rich plant extracts ameliorate the diabetes-associated consequences by reducing the glucose absorption, ROS production, oxidative stress, glomerular angiogenesis, lipid synthesis, and FoxO1 and adipose triglyceride lipase expressions, and improve the insulin secretion, insulin sensitivity, glucose tolerance, glucose uptake, glucose consumption, antioxidant activity. The literature search was made in Scopus, Google Scholar, PubMed using the keywords 'anthocyanin' and 'diabetes'. The documents were carefully checked for the relevance to the current manuscript and the selection was made without any chronological restriction. The present manuscript summarizes the updated reports on antihyperglycemic properties of ACN.

Functional Implications of HMG-CoA Reductase Inhibition on Glucose Metabolism

HMG-CoA reductase inhibitors, i.e. statins, are effective in reducing cardiovascular disease events but also in cardiac-related and overall mortality. Statins are in general well-tolerated, but currently the concerns are raised if statins may increase the risk of new-onset diabetes mellitus (NOD). In this review, the possible effects of statins on organs/tissues being involved in glucose metabolism, i.e. liver, pancreas, adipose tissue, and muscles, had been discussed. The net outcome seems to be inconsistent and often contradictory, which may be largely affected by in vitro experimental settings or/and in vivo animal conditions. The majority of studies point out statin-induced changes of regulations of isoprenoid metabolites and cell-associated cholesterol contents as predisposing factors related to the statin-induced NOD. On the other hand, it should be considered that dysfunctions of isoprenoid pathway and mitochondrial ATP production and the cholesterol homeostasis are already developed under (pre)diabetic and hypercholesterolemic conditions. In order to connect the basic findings with the clinical manifestation more clearly, further research efforts are needed.

Beneficial effects of anthocyanins against diabetes mellitus associated consequences-A mini review

Anthocyanins (ACN) are water-soluble pigments, belonging to flavonoids, and are present in almost all fruits, and vegetables at varying concentration. About 635 ACN were distinguished based on the position and number of methoxyl and hydroxyl moieties in the basic structure of ACN. Pelargonidin, cyanidin, delphinidin, malvidin, peonidin, and petunidin are extensively studied anthocyanidins. The absorption, bioavailability, metabolism, pharmacokinetics, molecular mechanism, and analytical techniques of several phytochemicals were described. The biological benefits (antidiabetic, anti-neuro-disorder, anti-cardiovascular diseases, anti-gastrointestinal diseases, and disorders) of flavonoids and ACN have been reported. Several in vitro, andin vivo reports demonstrated that ACN-rich plant extracts ameliorate the diabetes-associated consequences by reducing the glucose absorption, ROS production, oxidative stress, glomerular angiogenesis, lipid synthesis, and FoxO1 and adipose triglyceride lipase expressions, and improve the insulin secretion, insulin sensitivity, glucose tolerance, glucose uptake, glucose consumption, antioxidant activity. The literature search was made in Scopus, Google Scholar, PubMed using the keywords "anthocyanin" and "diabetes". The documents were carefully checked for the relevance to the current manuscript and the selection was made without any chronological restriction. The present manuscript summarizes the updated reports on antihyperglycemic properties of ACN.

Effects of metformin on insulin sensitivity and islet beta cell secretion in obesity patients / 基础医学与临床

Objective To investigate the effects of metformin on insulin sensitivity and secretion in patients with obesity and insulin resistance. Methods This study enrolled 42 obesity patients with insulin resistance who were regularly followed-up in Peking Union Medical College Hospital from September 2012 to May 2016. They were divided into two groups according to their different status of glucose metabolism: normal glucose tolerance( NGT) and impaired glucose regulation( IGR) . Life style intervention and metformin were given to all these patients. The antropometric and metabolic data were collected before treatment, 3 and 6 months after treatment respectively. Results 42 patients, aged (23.6±6.5) years, including 11 males and 31 females were enrolled. 19 of them were NGT and 23 were IGR (8 of IGT and 15 of IFG) . Among all these patients, fasting insulin was significantly higher at 3 months after treatment(P＜0.05).The same results were shown in group-NGT(P＜0.05). Fasting insulin was significantly lower at 6 months after treatment than at baseline among all patients( P＜0.05) . HOMA-IR showed no significant difference between the baseline and 3 months after treatment, but significantly higher at baseline and 3 months after treatment than 6 months after therapy( P＜0.001) . HOMA-beta was significantly( P＜0.001) lower be-fore treatment and 6 months treatment the effect was more significant than 3 months after treatment among all pa-tients. HOMA-beta was significantly lower at baseline in group-IGR than at baseline in group-NGT ( P＜0.05) . Conclusions The effect of metformin on insulin secretion is earlier than that of improving the insulin sensitivity in patients with obesity and insulin resistance. Metformin is more likely to promote insulin secretion in patients with normal glucose tolerance than those with IGR within 3 months of intervention.