This study explored the molecular mechanism underlying the Gegen Qinlian Decoction(GQD) promoting the differentiation of brown adipose tissue(BAT) to improve glucose and lipid metabolism disorders in diabetic rats. After the hypoglycemic effect of GQD on diabetic rats induced by high-fat diet combined with a low dose of streptozotocin was confirmed, the total RNA of rat BAT around scapula was extracted. Nuclear transcription genes Prdm16, Pparγc1α, Pparα, Pparγ and Sirt1, BAT marker genes Ucp1, Cidea and Dio2, energy expenditure gene Ampkα2 as well as BAT secretion factors Adpn, Fndc5, Angptl8, IL-6 and Rbp4 were detected by qPCR, then were analyzed by IPA software. Afterward, the total protein from rat BAT was extracted, and PRDM16, PGC1α, PPARγ, PPARα, SIRT1, ChREBP, AMPKα, UCP1, ADPN, NRG4, GLUT1 and GLUT4 were detected by Western blot. The mRNA expression levels of Pparγc1α, Pparα, Pparγ, Ucp1, Cidea, Ampkα2, Dio2, Fndc5, Rbp4 and Angptl8 were significantly increased(P<0.05) and those of Adpn and IL-6 were significantly decreased(P<0.05) in the GQD group compared with the diabetic group. In addition, Sirt1 showed a downward trend(P=0.104), whereas Prdm16 tended to be up-regulated(P=0.182) in the GQD group. IPA canonical pathway analysis and diseases-and-functions analysis suggested that GQD activated PPARα/RXRα and SIRT1 signaling pathways to promote the differentiation of BAT and reduce the excessive lipid accumulation. Moreover, the protein expression levels of PRDM16, PGC1α, PPARα, PPARγ, SIRT1, ChREBP, AMPKα, UCP1, GLUT1, GLUT4 and NRG4 were significantly decreased in the diabetic group(P<0.01), which were elevated after GQD intervention(P<0.05). Unexpectedly, the expression of ADPN protein in the diabetic group was up-regulated(P<0.01) as compared with the control group, which was down-regulated after the administration with GQD(P<0.01). This study indicated that GQD promoted BAT differentiation and maturity to increase energy consumption, which reduced the glucose and lipid metabolism disorders and thereby improved diabetes symptoms.
Adipose Tissue, Brown ; Animals ; Diabetes Mellitus, Experimental/genetics* ; Drugs, Chinese Herbal ; Fibronectins ; Glucose ; Lipid Metabolism ; Lipid Metabolism Disorders ; Rats

BACKGROUND: An early identification of the risk groups might be beneficial in reducing morbidities in patients with gestational diabetes mellitus (GDM). Therefore, this study aimed to assess the biochemical predictors of glycemic conditions, in addition to fasting indices of glucose disposal, to predict the development of GDM in later stage and the need of glucose-lowering medication.METHODS: A total of 574 pregnant females (103 with GDM and 471 with normal glucose tolerance [NGT]) were included. A metabolic characterization was performed before 15+6 weeks of gestation by assessing fasting plasma glucose (FPG), fasting insulin (FI), fasting C-peptide (FCP), and glycosylated hemoglobin (HbA1c). Thereafter, the patients were followed-up until the delivery.RESULTS: Females with NGT had lower levels of FPG, FI, FCP, or HbA1c at the early stage of pregnancy, and therefore, showed an improved insulin action as compared to that in females who developed GDM. Higher fasting levels of FPG and FCP were associated with a higher risk of developing GDM. Moreover, the predictive accuracy of this metabolic profiling was also good to distinguish the patients who required glucose-lowering medications. Indices of glucose disposal based on C-peptide improved the predictive accuracy compared to that based on insulin. A modified quantitative insulin sensitivity check index (QUICKIc) showed the best differentiation in terms of predicting GDM (area under the receiver operating characteristics curve [ROC-AUC], 72.1%) or need for pharmacotherapy (ROC-AUC, 83.7%).CONCLUSION: Fasting measurements of glucose and C-peptide as well as the surrogate indices of glycemic condition could be used for stratifying pregnant females with higher risk of GDM at the beginning of pregnancy.
Blood Glucose ; C-Peptide ; Diabetes, Gestational ; Drug Therapy ; Fasting ; Female ; Glucose Metabolism Disorders ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Insulin ; Insulin Resistance ; Metabolic Diseases ; Metabolism ; Pregnancy ; ROC Curve

The purpose of the present overview of meta-analysis is to summarize and critically assess the effect of isoflavones and genistein on glucose metabolism among the peri- and post-menopausal women. Two independent authors searched the databases of MEDLINE, Scopus and Cochrane Library for meta-analysis. Three databases were searched from inception to January 2018. Methodological quality of each meta-analysis of randomized controlled trials was evaluated using the AMSTAR (a measurement tool used to assess systematic reviews). Four meta-analyses were included to the current overview. Fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values were significantly lower in peri-menopausal and postmenopausal. Two meta-analyses showed that treatment with isoflavones could not alter fasting blood glucose. However, one meta-analysis depicted that isoflavones significantly improved blood glucose levels in non-Asian postmenopausal women. Treatment with genistein could have significant beneficial effects on fasting insulin, blood glucose and HOMA-IR in comparison to the control group. Regardless of the population, the treatment with genistein is effective in improving fasting insulin, HOMA-IR and glucose levels. Nevertheless, the high heterogeneity among studies and poor methodology of reviews made it difficult to draw a definite conclusion on the positive impacts of soy on glucose metabolism.
Blood Glucose ; Fasting ; Female ; Genistein ; Glucose Metabolism Disorders ; Glucose ; Humans ; Insulin ; Insulin Resistance ; Insulins ; Isoflavones ; Menopause ; Metabolism ; Population Characteristics

Obesity-related metabolic disorders can affect not only systemic health but also brain function. Recent studies have elucidated that amyloid beta deposition cannot satisfactorily explain the development of Alzheimer's disease (AD) and that dysregulation of glucose metabolism is a critical factor for the sporadic onset of non-genetic AD. Identifying the pathophysiology of AD due to changes in brain metabolism is crucial; however, it is limited in measuring changes in brain cognitive function due to metabolic changes in animal models. The touchscreen-based automated battery system, which is more accurate and less invasive than conventional behavioral test tools, is used to assess the cognition of mice with dysregulated metabolism. This system was introduced in humans to evaluate cognitive function and was recently back-translated in monkeys and rodents. We used outbred ICR mice fed on high-fat diet (HFD) and performed the paired associates learning (PAL) test to detect their visual memory and new learning ability loss as well as to assess memory impairment. The behavioral performance of the HFD mice was weaker than that of normal mice in the training but was not significantly associated with motivation. In the PAL test, the average number of trials completed and proportion of correct touches was significantly lower in HFD mice than in normal diet-fed mice. Our results reveal that HFD-induced metabolic dysregulation has detrimental effects on operant learning according to the percentage of correct responses in PAL. These findings establish that HFD-induced metabolic stress may have an effect in accelerating AD-like pathogenesis.
Alzheimer Disease ; Amyloid ; Animals ; Behavior Rating Scale ; Brain ; Cognition ; Cognition Disorders* ; Diet, High-Fat ; Glucose ; Haplorhini ; Humans ; Learning ; Memory ; Metabolism ; Mice* ; Mice, Inbred ICR ; Models, Animal ; Motivation ; Rodentia ; Stress, Physiological*

PURPOSE: Metabolic syndrome (MS) is characterized by a collection of interdependent disorders, including abdominal obesity, dyslipidemia, hyperglycemia, hypertension, and diabetes. The current study aimed to estimate the prevalence of MS in Qom, Iran. MATERIALS AND METHODS: A population-based screening program was conducted in the city of Qom, in 845 urban adult men over 25 years old in 2014. Abdominal obesity, fasting blood glucose (FBG), blood pressure, and the serum lipid profile were measured in subjects after fasting for at least 8 hours. MS was defined according to the Adult Treatment Panel III criteria. Data were analyzed using the chi-square test, t-test, and multiple logistic regression. RESULTS: The overall prevalence of MS was 23.0%, and the most common prevalent metabolic abnormalities associated with MS were low high-density lipoprotein cholesterol (< 40 mg/dL) in 34.3% of subjects, a waist circumference >102 cm in 33.9%, blood pressure ≥130/85 mmHg in 27.6%, fasting triglycerides (TG) ≥150 mg/dL in 25%, and FBG ≥110 mg/dL in 20.6%. A FBG level ≥110 mg/dL (odds ratio [OR]=4.85; 95% confidence interval [CI], 2.14~8.24), dyslipidemia (OR=3.51; 95% CI, 2.10~5.89), and a fasting TG ≥150 mg/dL were the most important factors contributing to MS. CONCLUSIONS: The prevalence of MS in men in Qom was higher than has been reported in other countries, but it was lower than the mean values that have been reported elsewhere in Iran. FBG was the most important factor contributing to MS, and all elements of the lipid profile showed important associations with MS.
Adult ; Blood Glucose ; Blood Pressure ; Cholesterol ; Dyslipidemias ; Fasting ; Humans ; Hyperglycemia ; Hyperlipidemias ; Hypertension ; Iran ; Lipid Metabolism Disorders ; Lipoproteins ; Logistic Models ; Male ; Mass Screening ; Obesity, Abdominal ; Prevalence ; Triglycerides ; Waist Circumference

Novelty seeking (NS) and antisocial personality (ASP) are commonly exhibited by those who suffer from addictions, such as substance abuse. NS has been suggested to be a fundamental aspect of ASP. To investigate the neurobiological substrate of NS and ASP, we tested the relationship between regional cerebral glucose metabolism and the level of NS, determining the differences between individuals with and without ASP. Seventy-two healthy adults (43 males, mean age±SD=38.8±16.6 years, range=20~70 years; 29 females, 44.2±20.1 years, range=19~72 years) underwent resting-state brain positron emission tomography (PET) 40 minutes after 18F-fluorodeoxyglucose (FDG) injection. Within 10 days of the FDG PET study, participants completed Cloninger's 240-item Temperament and Character Inventory (TCI) to determine NS scores. Participants with and without ASP were grouped according to their TCI profiles. Statistical parametric mapping analysis was performed using the FDG PET and TCI profile data. NS scores positively correlated with metabolism in the left anterior cingulate gyrus and the insula on both sides of the brain and negatively correlated with metabolism in the right pallidum and putamen. Participants with ASP showed differences in cerebral glucose metabolism across various cortical and subcortical regions, mainly in the frontal and prefrontal areas. These data demonstrate altered regional cerebral glucose metabolism in individuals with NS and ASP and inform our understanding of the neurobiological substrates of problematic behaviors and personality disorders.
Adult ; Antisocial Personality Disorder* ; Brain ; Electrons* ; Female ; Globus Pallidus ; Glucose* ; Gyrus Cinguli ; Humans ; Male ; Metabolism* ; Personality Disorders ; Positron-Emission Tomography* ; Putamen ; Substance-Related Disorders ; Temperament ; Viperidae

OBJECTIVETo study the effects of recombinant human growth hormone (r-hGH) replacement therapy on glucose and lipid metabolism and thyroid function in children with idiopathic short stature (ISS).

METHODSForty-seven ISS children with a mean age of 10±3 years treated between January 2009 and January 2013 were enrolled. All children underwent r-hGH replacement therapy for 3-24 months and were followed up once every 3 months. Fasting blood glucose (FBG), insulin (INS), blood lipids and thyroid function were measured before treatment and after 0-1 and 1-2 years of treatment.

RESULTSAfter treatment with r-hGH, there were no significant changes in FBG, INS, insulin sensitivity index (ISI), and FBG/INS ratio (FGIR), but the FGIR showed a declining trend. The percentage of patients with FGIR<7 (a marker of insulin resistance) was 13% before treatment compared to 18% 1-2 years after treatment. The atherosclerosis index decreased after r-hGH treatment, but there were no significant changes in total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and BMI. Furthermore, no significant change in thyroid function was observed after r-hGH therapy.

CONCLUSIONSr-hGH therapy can improve lipid metabolism, without significant impacts on thyroid function, FBG and INS. It seems to be a safe and reliable therapy for children with ISS. However, this therapy possibly reduces insulin sensitivity.

Adolescent ; Blood Glucose ; analysis ; Child ; Child, Preschool ; Female ; Glucose ; metabolism ; Growth Disorders ; drug therapy ; physiopathology ; Hormone Replacement Therapy ; Human Growth Hormone ; therapeutic use ; Humans ; Insulin ; blood ; Lipid Metabolism ; drug effects ; Male ; Thyroid Gland ; drug effects ; physiopathology

OBJECTIVETo analyze the clinical and SLC2A1 gene mutation characteristics of glucose transporter type 1 deficiency syndrome.

METHODThe detailed clinical manifestations of six cases were recorded. The laboratory tests including EEG, MRI, blood chemistry, and lumbar puncture were performed. SLC2A1 gene mutations were analyzed by PCR, DNA sequencing and multiplex ligation-dependent probe amplification (MLPA).

RESULTPatient 1, 2 and 3 had classical clinical symptoms including infantile onset seizures, development delay. Patient 4, 5 and 6 had non-classical clinical symptoms including paroxysmal behavior disturbance, weakness, ataxia, lethargy, especially after fasting or exercise, without severe seizures. The plasma glucose levels were normal. The CSF glucose levels decreased in all the six cases, ranged from 1.10 mmol/L to 2.45 mmol/L, the mean level was 1.68 mmol/L. The CSF glucose/plasma glucose ratios decreased, ranged from 0.16 to 0.51, the mean ratio was 0.34. Four patients had normal EEG. Two patients had focal and diffuse epileptiform discharge, and one of them also had paroxysmal occipital or generalized high-amplitude slow waves during awake and sleep time. MRI abnormalities were found in three patients, patient 1 with mild brain atrophy, patient 3 with bilateral ventricle plump, and patient 4 with high signals in T2 in the frontal and occipital white matter, interpreted as hypomyelination. SLC2A1 gene mutations were found in six cases. Patient 1 has large scale deletion in exon 2. In patient 2 to 6, the mutations were c.741 G>A (E247K), 599delA, 761delA, c.1148 C>A (P383H), c.1198 C>T (R400C) respectively. Two patients were treated with ketogenic diet. The seizures disappeared and development became normal. Three patients responded to frequent meals with snacks. One patient refused any treatments, the symptoms continued to exist.

CONCLUSIONThe clinical manifestations of glucose transporter type 1 deficiency syndrome are varied. The common symptoms included infantile onset seizures and various paroxysmal events. These neurologic symptoms generally fluctuated and were influenced by factors such as fasting or fatigue. This feature could be a very important clue for the diagnosis of GLUT1-DS. Lumbar puncture is recommended in patients with episodic CNS symptoms especially after fasting. GLUT1-DS is a treatable neurometabolic disorder, early diagnosis and treatment may improve the prognosis of the patients.

Biomarkers ; analysis ; Brain ; diagnostic imaging ; pathology ; Carbohydrate Metabolism, Inborn Errors ; diagnosis ; genetics ; therapy ; Child ; Child, Preschool ; DNA Mutational Analysis ; Diet, Ketogenic ; Electroencephalography ; Epilepsy ; diagnosis ; genetics ; therapy ; Female ; Follow-Up Studies ; Glucose Transporter Type 1 ; genetics ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Monosaccharide Transport Proteins ; deficiency ; genetics ; Movement Disorders ; diagnosis ; genetics ; therapy ; Mutation ; genetics ; Radiography

OBJECTIVETo characterize unknown glycometabolic state in patients with essential hypertension (EHT) and normotensive patients and determine which EHT patients are candidates for oral glucose tolerance tests (OGTTs).

METHODSThis cross-sectional study consecutively recruited 895 EHT patients and 486 normotensive patients. The data including blood glucose, blood pressure, blood lipids, angiography profiles, and left ventricular parameters were collected.

RESULTSOGTTs performed in all patients revealed that the prevalence of abnormal glucose metabolism (AGM) was significantly higher in EHT patients than in normotensive patients at both baseline (P<0.001) and post-OGTT analysis (P<0.001). In total, 76.4% of the individuals with impaired glucose tolerance and 78.2% of individuals with newly diagnosed diabetes would have remained undetected if OGTTs had not been performed. Newly diagnosed AGM was significantly correlated with the presence and severity of coronary stenosis and left ventricular structure abnormalities and dysfunction. EHT patients with fasting glucose ≥5.6 mmol/L, hypertension duration exceeding 10 years, coronary artery disease, high-sensitivity C-reactive protein >3 mg/L, or high levels of apoB/apoA-1 ratio were at high risk of AGM.

CONCLUSIONSAGM is more common in patients with EHT than in normotensive patients, and OGTTs is a cost-effective strategy to detect AGM in EHT patients.

Aged ; Blood Glucose ; metabolism ; Blood Pressure ; Cross-Sectional Studies ; Female ; Glucose Metabolism Disorders ; metabolism ; physiopathology ; Glucose Tolerance Test ; Humans ; Hypertension ; metabolism ; physiopathology ; Male ; Middle Aged

OBJECTIVETo detect the changes of the antioxidant level, cell cycle progression, necrosis and apoptosis, calcium ion concentration ([Ca2+] i) and mitochondrial membrane potential (deltapsim) in the model rats of impaired glucose regulation (IGR) induced by long-range high-fat diet, and to explore IGR-induced male reproductive injury and its mechanisms.

METHODSForty male Wistar rats were randomly divided into a normal control (n = 10) and an IGR model group (n = 30), and the IGR model was established by 20 weeks of long-range high-fat diet. Pathological changes in the rat spermatogenic cells were detected by HE staining; the content of malondialdehyde (MDA) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were measured with biochemical methods; changes in the cell cycle progression, necrosis and apoptosis were determined using flow cytometry with propidium iodide (PI) dyeing and the Annexin V-FITC kit, respectively, and [Ca2+]i and deltapsim were detected by flow cytometry with Fluo-3 and Rhodamine probe labeling, respectively.

RESULTSAfter 20 weeks of continuous high-fat diet, fasting blood glucose was kept at 6.1 - 7.0 mmol/L and blood glucose at 7.8 - 11.1 mmol/L after 2 h glucose load in 12 rats, with a 40% success rate of modeling. Lots of dividing spermatocytes and spermatids were seen in the tissue sections of the normal control rats under the microscope, but few or none in the IGR models. Compared with the normal controls, the IGR model rats showed remarkably increased MDA content and decreased SOD, CAT and GSH-Px activities in the testis tissue (P < 0.05 or P < 0.01) , reduced G0/G1 cells and increased G2/M cells (P < 0.05 or P < 0.01), decreased necrotic cells and increased apoptotic cells (P < 0.05 or P < 0.01), increased [Ca2+]i and decreased deltapsim (P < 0.01), but no significant changes in the percentages of S cells and normal cells.

CONCLUSIONIGR can cause spermatogenic cell division disorder in rats, which may be attributed to increased oxidative damage, decreased antioxidant enzyme activities, G2/M phase arrest, [Ca2+]i elevation, deltapsim reduction, and apoptosis of testicular cells.

Animals ; Apoptosis ; Cell Cycle ; Cell Division ; Diet, High-Fat ; Glucose Metabolism Disorders ; metabolism ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism ; Testis ; cytology ; metabolism