Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus, which is characterized in renal tubulointerstitial fibrosis (TIF). The current study was designed to investigate the protective effect of Jujuboside A (Ju A) on TIF in type 2 diabetes (T2DM) mice, and explore its underlying anti-fibrosis mechanism. A mouse T2DM model was established using high fat diet (HFD) feeding combined with intraperitoneal injection of streptozotocin (STZ). Then, diabetic mice were treated with Ju A (10, 20 and 40 mg·kg^-1·d^-1, i.g.) for 12 weeks. Results showed that administration of Ju A not only down-regulated fasting blood glucose (FBG) levels, but also improved hyperlipidemia and renal function in diabetic mice. Moreover, the reduced ECM accumulation was observed in the renal cortex of Ju A treated diabetic mice, while the TIF progression was also attenuated by Ju A through blocking the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs). Further mechanism studies showed that Ju A treatment effectively down-regulated the protein expression and subsequent nuclear translocation of Yin Yang 1 (YY1) in the renal cortex of diabetic mice, and reduced the levels of transforming growth factor-β1 (TGF-β1) in the serum and renal cortex of Ju A treated mice. According to invitro studies, the up-regulated YY1/TGF-β1 signaling pathway was restored by Ju A in high glucose (HG) cultured HK-2 cells. Taken together, these findings demonstrated that Ju A can ameliorate the TIF of DN through down-regulating the YY1/TGF-β1 signaling pathway.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental/metabolism* ; Diabetes Mellitus, Type 2/drug therapy* ; Diabetic Nephropathies/metabolism* ; Fibrosis ; Mice ; Saponins ; Signal Transduction ; Streptozocin ; Transforming Growth Factor beta1/metabolism*

Exercise is vital for diabetics to improve their blood glucose level. However, the quantitative relationship between exercise modes (including types, intensity, time, etc.) and the blood glucose is still not clear. In order to answer these questions, this paper established a blood glucose metabolic model based on ordinary differential equation method. Furthermore, a silico method was adopted to study the effects of different aerobic exercise intensities (light, moderate and vigorous) on blood glucose and optimal strategies of insulin infusion for type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Additionally, the universality of proposed model and insulin infusion strategies was verified based on 1 000 virtual diabetes patients' simulation. The experimental results showed that: (1) Vigorous-intensity aerobic exercise may result in hypoglycemia (< 3.89 mmol/L), which was so harmful to health that diabetics should avoid. Compared with moderate-intensity exercise, the light-intensity aerobic exercise intuitively lowered blood glucose slowly and caused a relative long high-blood-glucose (> 6.11 mmol/L) period, however, its overall blood glucose risk index (BGRI) was lower. (2) Insulin dosage of the optimized strategies decreased by 50% and 84% for T1DM and T2DM when they did moderate intensity exercise. As for light intensity exercise, the dosage of insulin was almost the same as they didn't do exercise, but BGRI decreased significantly. (3) The simulations of 1 000 virtual diabetic patients manifested that the proposed model and the insulin infusion strategies had good universality. The results of this study can not only help to improve the quantitative understanding about the effects of aerobic exercise on blood glucose of diabetic patients, but also contribute to the regulation and management of blood glucose in exercise mode.
Blood Glucose ; metabolism ; Computer Simulation ; Diabetes Mellitus, Type 1 ; drug therapy ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; Exercise ; Humans ; Insulin ; administration & dosage ; Models, Theoretical

Nonalcoholic fatty liver disease (NAFLD) and type 2 Diabetes Mellitus (T2DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract (MCE; 10 g·kg·d) lowered the blood lipid levels and reversed insulin resistance (IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element binding protein (ChREBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and mRNA expression levels of SREBP-1c and ChREBP. In conclusion, down-regulation of SREBP-1c and ChREBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2DM associated with NAFLD.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; Diabetes Mellitus, Type 2 ; blood ; chemically induced ; drug therapy ; metabolism ; Diet, High-Fat ; adverse effects ; Disease Models, Animal ; Down-Regulation ; drug effects ; Insulin ; blood ; Insulin Resistance ; physiology ; Lipid Metabolism ; drug effects ; genetics ; Liver ; drug effects ; physiopathology ; Male ; Morus ; Non-alcoholic Fatty Liver Disease ; blood ; chemically induced ; drug therapy ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Streptozocin

Xiao Ke Qing (XKQ) granule has been clinically used to treat type 2 diabetes mellitus (T2DM) for 10 years in Chinese traditional medication. However, its mechanisms against hyperglycemia remain poorly understood. This study aims to investigate XKQ mechanisms on diabetes and diabetic liver disease by using the KKAy mice model. Our results indicate that XKQ can significantly reduce food and water intake. XKQ treatment also remarkably decreases both the fasting blood glucose and blood glucose in the oral glucose tolerance test. Additionally, XKQ can significantly decrease the serum alanine aminotransferase level and liver index and can alleviate the fat degeneration in liver tissues. Moreover, XKQ can ameliorate insulin resistance and upregulate the expression of IRS-1, PI3K (p85), p-Akt, and GLUT4 in the skeletal muscle of KKAy mice. XKQ is an effective drug for T2DM by ameliorating insulin resistance and regulating the PI3K/Akt signaling pathway in the skeletal muscle.
Animals ; Blood Glucose ; drug effects ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Female ; Glucose Tolerance Test ; Glucose Transporter Type 4 ; metabolism ; Hypoglycemic Agents ; pharmacology ; Insulin ; blood ; Insulin Resistance ; Liver ; drug effects ; pathology ; Mice ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; drug effects

Objective To assess the efficiency and safety of a novel sodium-glucose co-transporter 2 (SGLT2) inhibitor-SGLT2 inhibitors, in combination with insulin for type 1 diabetes mellitus (T1DM). Methods We searched Medline, Embase, and the Cochrane Collaboration Library to identify the eligible studies published between January 2010 and July 2016 without restriction of language. The Food and Drug Administration (FDA) data and ClinicalTrials (http://www.clinicaltrials.gov) were also searched. The included studies met the following criteria: randomized controlled trials; T1DM patients aged between 18 and 65 years old; patients were treated with insulin plus SGLT2 inhibitors for more than 2 weeks; patients' glycosylated hemoglobin (HbA1c) levels were between 7% and 12%. The SGLT2 inhibitors group was treated with SGLT2 inhibitors plus insulin, and the placebo group received placebo plus insulin treatment. The outcomes should include one of the following items: fasting blood glucose, HbA1c, glycosuria, or adverse effects. Data were analyzed by two physicians independently. The risk of bias was evaluated by using the Cochrane Collaboration's Risk of Bias tool and heterogeneity among studies was assessed using Chi-square test. Random effect model was used to analyze the treatment effects with Revman 5.3.Results Three trials including 178 patients were enrolled. As compared to the placebo group, SGLT2 inhibitor absolutely decreased fasting blood glucose [mean differences (MD) -2.47 mmol/L, 95% confidence interval (CI) -3.65 to -1.28, P<0.001] and insulin dosage (standardized MD -0.75 U, 95%CI -1.17 to -0.33, P<0.001). SGLT2 inhibitors could also increase the excretion of urine glucose (MD 131.09 g/24 h, 95%CI 91.79 to 170.39, P<0.001). There were no significant differences in the incidences of hyperglycemia [odds ratio (OR) 1.82, 95%CI 0.63 to 5.29, P=0.27], urinary tract infection (OR 0.95, 95%CI 0.19 to 4.85, P=0.95), genital tract infection (OR 0.27, 95%CI 0.01 to 7.19, P=0.43), and diabetic ketoacidosis (OR 6.03, 95%CI 0.27 to 135.99, P=0.26) between the two groups.Conclusion SGLT2 inhibitors combined with insulin might be an efficient and safe treatment modality for T1DM patients.
Adolescent ; Adult ; Aged ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 1 ; blood ; drug therapy ; Drug Therapy, Combination ; methods ; Fasting ; blood ; Female ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemic Agents ; adverse effects ; therapeutic use ; Insulin ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Randomized Controlled Trials as Topic ; Sodium-Glucose Transporter 2 ; antagonists & inhibitors

The present study aimed at exploring the therapeutic potential of standard extract of Bombax ceiba L. leaves (BCE) in type 2 diabetic mellitus (T2DM). Oral administration of BCE at doses of 70, 140, and 280 mg·kg, to the normal rats and the high-fat-diet- and streptozotocin-induced T2DM rats were carried out. Effects of BCE on blood glucose, body weight, and a range of serum biochemical parameters were tested, and histopathological observation of pancreatic tissues was also performed. HPLC-ESI-Q/TOF-MS/MS analysis indicated that the chemical composition of BCE mainly contained mangiferin, isoorientin, vitexin, isomangiferin, isovitexin, quercetin hexoside, 2'-trans-O-cumaroyl mangiferin, and nigricanside. BCE caused a significant decrease in the concentrations of fasting blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride, low density lipoprotein-cholesterol, serum insulin, and malondialdehyde, and increases in oral glucose tolerance, high density lipoprotein-cholesterol, and superoxide dismutase in the T2DM model rats. Moreover, considerable pancreatic β-cells protection effect and stimulation of insulin secretion from the remaining pancreatic β-cells could be observed after BCE treatment. The results indicated that BCE exhibited an excellent hypoglycemic activity, and alleviated dyslipidemia which is associated with T2DM. Antioxidant activity and protecting pancreatic β-cells are the possible mechanisms involved in anti-diabetic activity of BCE.
Animals ; Antioxidants ; administration & dosage ; chemistry ; isolation & purification ; Blood Glucose ; metabolism ; Bombax ; chemistry ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; Humans ; Hypoglycemic Agents ; administration & dosage ; chemistry ; isolation & purification ; Hypolipidemic Agents ; administration & dosage ; chemistry ; isolation & purification ; Male ; Plant Extracts ; administration & dosage ; chemistry ; isolation & purification ; Plant Leaves ; chemistry ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the long-term clinical effect of Tangyiping Granules (, TYP) on patients with impaired glucose tolerance (IGT) to achieve normal glucose tolerance (NGT) and hence preventing them from conversion to diabetes mellitus (DM).

METHODSIn total, 127 participants with IGT were randomly assigned to the control (63 cases, 3 lost to follow-up) and treatment groups (64 cases, 4 lost to follow-up) according to the random number table. The control group received lifestyle intervention alone, while the patients in the treatment group took orally 10 g of TYP twice daily in addition to lifestyle intervention for 12 weeks. The rates of patients achieving NGT or experiencing conversion to DM as main outcome measure were observed at 3, 12, and 24 months after TYP treatment. The secondary outcome measures included fasting plasma glucose (FPG), 2-h postprandial plasma glucose (2hPG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), 2-h insulin (2hINS), homeostatic model assessment of insulin resistance (HOMA-IR), blood lipid and patients' complains of Chinese medicine (CM) symptoms before and after treatment.

RESULTSA higher proportion of the treatment group achieved NGT compared with the control group after 3-, 12- and 24-month follow-up (75.00% vs. 43.33%, 58.33% vs. 35.00%, 46.67% vs. 26.67%, respectively, P<0.05). The IGT to DM conversion rate of the treatment group was significantly lower than that of the control group at the end of 24-month follow-up (16.67% vs. 31.67%, P<0.05). Before treatment, FPG, 2hPG, HbA1c, FINS, 2hINS, HOMA-IR, triglyceride (TG), total cholesterol, low- and high-density lipoprotein cholesterol levels had no statistical difference between the two groups (P>0.05). After treatment, the 2hPG, HbA1c, HOMA-IR, and TG levels of the treatment group decreased significantly compared with those of the control group (P<0.05). CM symptoms such as exhaustion, irritability, chest tightness and breathless, spontaneous sweating, constipation, and dark thick and greasy tongue were significantly improved in the treatment group as compared with the control group (P<0.05). No severe adverse events occurred.

CONCLUSIONTYP administered at the IGT stage with a disciplined lifestyle delayed IGT developing into type 2 DM.

Blood Glucose ; metabolism ; Blood Platelets ; drug effects ; metabolism ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Erythrocytes ; drug effects ; metabolism ; Female ; Glucose Intolerance ; blood ; drug therapy ; Humans ; Insulin ; blood ; Kidney ; drug effects ; physiopathology ; Leukocytes ; drug effects ; metabolism ; Lipids ; blood ; Liver ; drug effects ; physiopathology ; Male ; Middle Aged ; Time Factors

OBJECTIVETo assess whether the dietary supplement (bromelain) has the potential to reduce plasma fibrinogen and other cardiovascular disease (CVD) risk factors in patients with diabetes.

METHODSThis randomized placebo controlled, double blind, parallel design, efficacy study was carried out in China and investigated the effect of 12 weeks of bromelain (1,050 mg/day) on plasma fibrinogen. This randomized controlled trial (RCT) recruited 68 Chinese diabetic patients [32 males and 36 females; Han origin, mean age of 61.26 years (standard deviation (SD), 12.62 years)] with at least one CVD risk factor. Patients were randomized into either bromelain or placebo group. While bromelain group received bromelain capsule, the placebo group received placebo capsule which consisted inert ingredient and has no treatment effect. Subjects were required to take 1,050 mg (3×350 mg) of either bromelain or starch-filled placebo capsules, two to be taken (2×350 mg) after breakfast and another (350 mg) after dinner, daily for 12 weeks. Plasma fibrinogen, CVD risk factors and anthropometric indicators were determined at baseline and at 12 weeks.

RESULTSThe change in the fibrinogen level in the bromelain group at the end of the study showed a mean reduction of 0.13 g/L (standard deviation (SD) 0.86g/L) compared with the mean reduction of 0.36 g/L (SD 0.96 g/L) for the placebo group. However, there was no significant difference in the mean change in fibrinogen between the placebo and bromelain groups (mean difference=0.23g/L (SD 0.22 g/L), =0.291). Similarly, the difference in mean change in other CVD risk factors (blood lipids, blood pressure), blood glucose, C-reactive protein and anthropometric measures between the bromelain and placebo groups was also not statistically significant. Statistical differences in fibrinogen between bromelain and placebo groups before the trial despite randomization may have influenced the results of this study.

CONCLUSIONThis RCT failed to show a beneficial effect in reducing fibrinogen or influencing other selected CVD risk factors but suggests other avenues for subsequent research on bromelain.

Blood Glucose ; Bromelains ; pharmacology ; therapeutic use ; C-Reactive Protein ; metabolism ; Cardiovascular Diseases ; blood ; complications ; drug therapy ; Demography ; Diabetes Mellitus, Type 2 ; blood ; complications ; drug therapy ; Double-Blind Method ; Female ; Fibrinogen ; metabolism ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Placebos ; Risk Factors ; Treatment Outcome

OBJECTIVETo observe the effect and mechanism of curcumin derivative B06 on kidney from rats with hyperlipidemia and type 2 diabetes.

METHODSThirty five male SD rats were randomly divided into five groups(n = 7): the normal control group, high-fat group, high-fat + B06-treatd group, diabetic group, diabetic + B06-treated group. After fed with high-fat diet for 4 weeks, the later two groups were in- jected with streptozotocin intraperitoneally to induce type 2 diabetes mellitus. B06-treated groups were given B06 by gavage at a dosage of 0.2 mg/kg . d for 8 weeks. After the treatment, the serum creatinine, blood urea nitrogen and uric acid were detected biochemically, the morphology of kidney was observed with light and transmission electron microscopy, the expression of collagen fibers was observed with Masson staining, the protein expression of collogen IV and fibronectin in kidney were determined by Immunohistochemistry.

RESULTSIt was showed that the levels of the serum creatinine and blood urea nitrogen elevated significantly in diabetic group. In high-fat and diabetic groups, increased glomerular mesangial matrix and collagen fiber and thicken glomerular basal membrane were observed under light microscopy, swelling and fusion of foot process were found under electron microscope; increased green matrix within glomeruli was observed under Masson staining. collogen IV and fibronectin protein expression were significantly enhanced in high-fat group and diabetic group. After B06's intervention, the levels of serum creatinine and blood urea nitrogen were decreased in diabetic groups, the morphological change of kidney was obviously relieved, Collogen IV and fibronectin protein expression reduced.

CONCLUSIONCurcumin derivative B06 exerts a protective effect on kidney in type 2 diabetic rats, reduced expressions of collogen IV and fibronectin, inhibition of the accumulation of extracellular matrix and glomerular mesangial proliferation, and then prevention of renal fibrosis may be the mechanism.

Animals ; Blood Urea Nitrogen ; Collagen Type IV ; metabolism ; Creatinine ; blood ; Curcumin ; pharmacology ; Diabetes Mellitus, Experimental ; complications ; drug therapy ; Diabetes Mellitus, Type 2 ; Drugs, Chinese Herbal ; Fibronectins ; metabolism ; Kidney ; metabolism ; physiopathology ; Kidney Diseases ; drug therapy ; Male ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Uric Acid ; blood

[To explore the effect of Humifuse Euphorbia Herb ( HEH) on alleviating insulin resistance in type 2 diabetic KK-Ay mice. Totally 40 KK-Ay mice fed with high-fat diet were divided into four groups: the metformin group, the model group, the HEH low-dose group and the HEH high-dose group, and orally administrated with metformin hydrochloride (250 mg x kg(-1)), distilled water, humifuse euphorbia herb 1 g x kg(-1) and 2 g x kg(-1). Besides, C57BL/6J mice with ordinary feed were taken as the normal control group and orally administrated with equal distilled water. The oral administration for the five groups lasted for eight weeks. Before and after the experiment, weight, fasting glucose and insulin tolerance were determined. The morphological changes in pancreas were observed through hematoxylin-eosin (HE) staining on pancreatic tissue sections. The serum insulin, TNF-α, IL-6, adiponectin (ADPN) and leptin (LEP) were detected by ELISA. The results showed that HEH could reduce weight and fasting glucose in KK-Ay mice, alleviate hyperinsulinemia, reduce blood glucose-time AUC, increase 30-min blood glucose decline rate, relieve insulin resistance, significantly ameliorate the pathomorphological changes in pancreas in each group, decrease serum TNF-α, IL-6 and leptin levels in KK-Ay mice and rise serum ADPN level. This study proved that humifuse euphorbia herb can ameliorate the insulin resistance in KK-Ay mice, and its mechanism may be related to the effect on inflammatory factors and adipocytokines.
Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Euphorbia ; chemistry ; Humans ; Insulin ; metabolism ; Insulin Resistance ; Interleukin-6 ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Tumor Necrosis Factor-alpha ; genetics ; metabolism