PURPOSE: Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. MATERIALS AND METHODS: Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. RESULTS: Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. CONCLUSION: Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.
Albuminuria ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Curcumin/*pharmacology ; Diabetes Mellitus, Type 2/*metabolism/urine ; Diabetic Nephropathies/complications/*drug therapy/metabolism/pathology ; Gene Expression/drug effects ; Inflammation ; Kidney/drug effects/metabolism/physiopathology ; Kidney Glomerulus/metabolism/physiopathology ; Lipid Metabolism/*drug effects ; Male ; Malondialdehyde/metabolism/urine ; Oxidative Stress/*drug effects ; Rats ; Rats, Inbred OLETF ; Rats, Long-Evans ; Superoxide Dismutase/metabolism

To study the therapeutic effect and possible mechanism of icariin on myocardial ischemia-reperfusion injury ( MIRI) model in diabetes rats. The model of diabetic rats were induced by Streptozotocin (STZ), then the model of MIRI was established by ligating the reversible left anterior descending coronary artery for 30 min, and then reperfusing for 120 min. totally 40 male SD were randomly divided into five groups: the control group (NS), the ischemia reperfusion group (NIR), the diabetes control group (MS), the diabetic ischemia reperfusion group (MIR) and the diabetic ischemia reperfusion with icariin group (MIRI). The changes in blood glucose, body weight and living status were observed; the enzyme activity of serum CK-MB, LDH, GSH-Px and myocardium SOD and the content MDA and NO in myocardium were detected; the myocardial pathological changes were observed by HE staining; the myocardial Caspase-3, the Bcl-2, Bax protein expressions were detected by Western blot. The result showed that the diabetes model was successfully replicated; myocardial ischemia-reperfusion injury was more serious in diabetes rats; icariin can increase NO, SOD, GSH-Px, Bcl-2 protein expression, decrease MDA formation, CK-MB and LDH activities and Caspase-3 and Bcl-2 protein expressions and myocardial damage. The result suggested that icariin may play a protective role against ischemia reperfusion myocardial injury in diabetes rats by resisting oxidative stress and inhibiting cell apoptosis.
Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Creatine Kinase ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; Drugs, Chinese Herbal ; administration & dosage ; Flavonoids ; administration & dosage ; Humans ; Ischemia ; drug therapy ; etiology ; physiopathology ; Male ; Malondialdehyde ; metabolism ; Myocardial Reperfusion Injury ; drug therapy ; etiology ; metabolism ; physiopathology ; Myocardium ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; bcl-2-Associated X Protein ; metabolism

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

Hypoglycemia is a major barrier to achieving the glycemic goal in patients with type 2 diabetes. In particular, severe hypoglycemia, which is defined as an event that requires the assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions, is a serious clinical concern in patients with diabetes. If severe hypoglycemia is not managed promptly, it can be life threatening. Hypoglycemia-associated autonomic failure (HAAF) is the main pathogenic mechanism behind severe hypoglycemia. Defective glucose counter-regulation (altered insulin secretion, glucagon secretion, and an attenuated increase in epinephrine during hypoglycemia) and a lack of awareness regarding hypoglycemia (attenuated sympathoadrenal activity) are common components of HAAF in patients with diabetes. There is considerable evidence that hypoglycemia is an independent risk factor for cardiovascular disease. In addition, hypoglycemia has a significant influence on the quality of life of patients with diabetes. To prevent hypoglycemic events, the setting of glycemic goals should be individualized, particularly in elderly individuals or patients with complicated or advanced type 2 diabetes. Patients at high-risk for the future development of severe hypoglycemia should be selected carefully, and intensive education with reinforcement should be implemented.
Autonomic Nervous System/physiopathology ; Biological Markers/blood ; Blood Glucose/*drug effects/metabolism ; Diabetes Mellitus, Type 2/blood/complications/diagnosis/*drug therapy/physiopathology ; Health Knowledge, Attitudes, Practice ; Humans ; Hypoglycemia/blood/chemically induced/epidemiology/physiopathology/*prevention & control ; Hypoglycemic Agents/*adverse effects ; Incidence ; Patient Education as Topic ; Prevalence ; Prognosis ; Risk Assessment ; Risk Factors

BACKGROUND/AIMS: Recent epidemiological studies revealed a striking inverse relationship between vitamin D levels, glucose intolerance/insulin resistance (IR), and cardiovascular disease. However, few interventional studies have evaluated the effect of vitamin D supplementation on cardiovascular risk, such as IR and arterial stiffness, in diabetes. We investigated the role of vitamin D supplementation on cardiovascular risk in type 2 diabetes patients, including metabolic parameters, IR, and arterial stiffness. METHODS: We enrolled patients who were taking antidiabetic medications or managed their diabetes using lifestyle changes. We excluded patients who were taking vitamin D or calcium supplements. We randomized participants into the vitamin D group (cholecalciferol 2,000 IU/day + calcium 200 mg/day, n = 40) or the placebo group (calcium 200 mg/day, n = 41). We compared their IR (homeostasis model of assessment [HOMA]-IR) and arterial stiffness (brachial-ankle pulse wave velocity and radial augmentation index) before and after 24 weeks of intervention. RESULTS: The baseline characteristics of the two groups were similar. A total of 62 participants (placebo, 30; vitamin D, 32) completed the study protocol. At the end of the study period, the 25-hydroxyvitamin D [25(OH)D] levels were significantly higher in the vitamin D group than in the placebo group (35.4 +/- 8.5 ng/mL vs. 18.4 +/- 7.3 ng/mL, p < 0.001). There was no difference in HOMA-IR or changes in arterial stiffness (placebo, 21, vitamin D, 24) between the groups. CONCLUSIONS: Our data suggest that high-dose vitamin D supplementation might be effective in terms of elevating 25(OH)D levels. However, we identified no beneficial effects on cardiovascular risk in type 2 diabetes, including IR and arterial stiffness.
Calcium, Dietary/administration & dosage ; Cholecalciferol/*administration & dosage ; Diabetes Mellitus, Type 2/complications/*drug therapy/physiopathology ; Double-Blind Method ; Female ; Humans ; *Insulin Resistance ; Male ; Middle Aged ; Prospective Studies ; Vascular Stiffness/*drug effects ; Vitamin D/analogs & derivatives/blood ; Vitamin D Deficiency/blood/complications/drug therapy

We aimed to investigate that complete revascularization (CR) would be associated with a decreased mortality in patients with multivessel disease (MVD) and reduced left ventricular ejection fraction (LVEF). We enrolled a total of 263 patients with MVD and LVEF <50% who had undergone percutaneous coronary intervention with drug-eluting stent between March 2003 and December 2010. We compared major adverse cardiac and cerebrovascular accident (MACCE) including all-cause death, myocardial infarction, any revascularization, and cerebrovascular accident between CR and incomplete revascularization (IR). CR was achieved in 150 patients. During median follow-up of 40 months, MACCE occurred in 52 (34.7%) patients in the CR group versus 51 (45.1%) patients in the IR group (P=0.06). After a Cox regression model with inverse-probability-of-treatment-weighting using propensity score, the incidence of MACCE of the CR group were lower than those of the IR group (34.7% vs. 45.1%; adjusted hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.44-0.95, P=0.03). The rate of all-cause death was significantly lower in patients with CR than in those with IR (adjusted HR, 0.48; 95% CI, 0.29-0.80, P<0.01). In conclusion, the achievement of CR with drug-eluting stent reduces long-term MACCE in patients with MVD and reduced LVEF.
Age Factors ; Aged ; Coronary Artery Disease/*drug therapy/mortality/physiopathology ; Diabetes Mellitus, Type 2/complications ; *Drug-Eluting Stents ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Myocardial Infarction/etiology ; Myocardial Revascularization ; Percutaneous Coronary Intervention/adverse effects ; Proportional Hazards Models ; Renal Insufficiency, Chronic/complications ; Retrospective Studies ; Sex Factors ; Treatment Outcome ; Ventricular Dysfunction, Left/physiopathology

No abstract available.
Antidiarrheals/*therapeutic use ; Benzimidazoles/*therapeutic use ; Diabetes Mellitus, Type 2/*complications ; Diarrhea/diagnosis/*drug therapy/etiology/physiopathology ; Endoscopy, Gastrointestinal ; Gastrointestinal Transit/*drug effects ; Humans ; Male ; Middle Aged ; Serotonin 5-HT3 Receptor Antagonists/*therapeutic use ; Treatment Outcome

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).
Adiponectin/blood ; Aged ; Aged, 80 and over ; Atherosclerosis/complications/drug therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin/therapeutic use ; Prospective Studies ; Pyrazines/pharmacology/*therapeutic use ; Regression Analysis ; Triazoles/pharmacology/*therapeutic use ; Vasodilation/drug effects ; Vasodilator Agents/therapeutic use

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).
Adiponectin/blood ; Aged ; Aged, 80 and over ; Atherosclerosis/complications/drug therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin/therapeutic use ; Prospective Studies ; Pyrazines/pharmacology/*therapeutic use ; Regression Analysis ; Triazoles/pharmacology/*therapeutic use ; Vasodilation/drug effects ; Vasodilator Agents/therapeutic use

The insulin resistance (IR) and the active ingredients of traditional Chinese medicine and their mechanisms to improve IR in the last 3 years are summarized. Retrieve, classify and arrange the recent documentations of china and abroad. IR can drive the occurrence and progress of type 2 diabetes mellitus (T2DM), and there are several molecular mechanisms for the occurrence of IR. IR has been a research focus of diabetes, the control strategies of T2DM have been changed from the "hypoglycemic therapy" into "improve the IR and IR-related metabolic abnormalities, and make a comprehensive prevention and treatment of cardiovascular risk factors". It is demonstrated by experiments that a variety of active ingredients of traditional Chinese medicine can improve IR through different mechanisms to treat diabetes mellitus.
Animals ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; physiopathology ; Drugs, Chinese Herbal ; analysis ; therapeutic use ; Humans ; Insulin Resistance ; Medicine, Chinese Traditional