Alkaline Phosphatase ; metabolism ; Asian Continental Ancestry Group ; Bone Density Conservation Agents ; therapeutic use ; China ; Denosumab ; therapeutic use ; Diabetes Mellitus, Type 2 ; complications ; Female ; Humans ; Hyperlipidemias ; complications ; Hypertension ; complications ; Middle Aged ; Osteitis Deformans ; complications ; diagnostic imaging ; drug therapy ; metabolism ; Pelvic Bones ; diagnostic imaging ; Renal Insufficiency, Chronic ; complications ; Singapore ; Tibia ; diagnostic imaging ; Treatment Outcome

The study aimed to investigate the intervening role of Didang decoction (DDD) at different times in macrovascular endothelial defense function, focusing on its effects on the AMP-activated protein kinase (AMPK) signaling pathway. The effects of DDD on mitochondrial energy metabolism were also investigated in rat aortic endothelial cells (RAECs). Type 2 diabetes were induced in rats by streptozotocin (STZ) combined with high fat diet. Rats were randomly divided into non-intervention group, metformin group, simvastatin group, and early-, middle-, late-stage DDD groups. Normal rats were used as control. All the rats received 12 weeks of intervention or control treatment. Western blots were used to detect the expression of AMP-activated protein kinase α1 (AMPKα1) and peroxisome proliferator-activated receptor 1α (PGC-1α). Changes in the intracellular AMP and ATP levels were detected with ELISA. Real-time-PCR was used to detect the mRNA level of caspase-3, endothelial nitric oxide synthase (eNOS), and Bcl-2. Compared to the diabetic non-intervention group, a significant increase in the expression of AMPKα1 and PGC-1α were observed in the early-stage, middle-stage DDD groups and simvastatin group (P < 0.05). The levels of Bcl-2, eNOS, and ATP were significantly increased (P < 0.05), while the level of AMP and caspase-3 were decreased (P < 0.05) in the early-stage DDD group and simvastatin group. Early intervention with DDD enhances mitochondrial energy metabolism by regulating the AMPK signaling pathway and therefore may play a role in strengthening the defense function of large vascular endothelial cells and postpone the development of macrovascular diseases in diabetes.
AMP-Activated Protein Kinases ; metabolism ; Adenosine Triphosphate ; metabolism ; Animals ; Aorta ; drug effects ; metabolism ; Cardiovascular Diseases ; metabolism ; prevention & control ; Caspase 3 ; metabolism ; Diabetes Mellitus, Experimental ; complications ; drug therapy ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; metabolism ; Diptera ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endothelial Cells ; drug effects ; metabolism ; Endothelium, Vascular ; drug effects ; metabolism ; Energy Metabolism ; drug effects ; Leeches ; Mitochondria ; drug effects ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; metabolism ; Phytotherapy ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Prunus persica ; Rats, Sprague-Dawley ; Rheum ; Signal Transduction

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

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 investigate the protective effects of irbesartan against cardiac inflammation associated with diabetes and obesity in the db/db mouse model of type 2 diabetes and explore the underlying mechanisms.

METHODSTwenty- four 10-week-old diabetic db/db mice were equally randomized into irbesartan treatment (50 mg/kg per day) group and model group, using 12 nondiabetic littermates (db/+) as the controls, The mice were treated with irbesartan or saline vehicle for 16 consecutive weeks, after which the heart pathology was observed and the heart weight, body weight, and serum levels of fasting blood glucose (FBG), total cholesterol(TC), and triglycerides(TG) were measured. The expression of nuclear factor-kappaB (NF-κB) p65 in the myocardium was assessed with immunohistochemistry, the protein levels of P-IκBα ,IκBα and β-actin were analyzed with Western blotting, and the pro-inflammatory cytokines IL-6 and TNF-α mRNA were detected using quantitative real-time PCR (qPCR).

RESULTSCompared with db/+ mice, the saline-treated db/db mice developed obesity, hyperglycemia and hyperlipidemia (P<0.01). Histopathological examination of the heart tissue revealed inflammatory cell infiltration, increased myocardial interstitium and disorders of myocardial fiber arrangement. The diabetic mice showed increased P-IαBα and decreased IκBα protein levels, enhanced activity and expression of NF-κB in the hearts, and increased mRNA expression of IL-6 and TNF-α in the myocardium. These abnormalities were all associated with increased inflammatory response. Treatment with irbesartan improved the heart architecture and attenuated high glucose-induced inflammation in the diabetic mice.

CONCLUSIONTreatment with irbesartan attenuates cardiac inflammation in type 2 diabetic db/db mice, and this effect was probably associated with the suppression of cardiac angiotensin II and NF-κB signaling pathway.

Actins ; metabolism ; Angiotensin II ; metabolism ; Animals ; Biphenyl Compounds ; pharmacology ; Cardiovascular Diseases ; drug therapy ; Diabetes Mellitus, Experimental ; complications ; Diabetes Mellitus, Type 2 ; complications ; Inflammation ; drug therapy ; Interleukin-6 ; metabolism ; Mice ; Obesity ; complications ; Random Allocation ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Tetrazoles ; pharmacology ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

PURPOSE: The aim of this study was to examine the effects of all-trans retinoic acid (ATRA) on diabetic nephropathy. MATERIALS AND METHODS: We measured amounts of urinary albumin excretion (UAE) after administrating ATRA to Otsuka Long-Evans Tokushima Fatty (OLETF) rats. In order to understand the mechanism of action for ATRA, we administrated ATRA to examine its inhibitory action on the production of transforming growth factor-beta1 (TGF-beta1), protein kinase C (PKC), and reactive oxidative stress (ROS) in cultured rat mesangial cells (RMCs). RESULTS: After 16 weeks of treatment, UAE was lower in the ATRA-treated OLETF rats than in the non-treated OLETF rats (0.07+/-0.03 mg/mgCr vs. 0.17+/-0.15 mg/mgCr, p<0.01). After incubation of RMCs in media containing 30 or 5 mM of glucose, treatment with ATRA showed time- and dose-dependent decreases in TGF-beta1 levels and ROS. Moreover, ATRA treatment showed a dose-dependent decrease in PKC expression. CONCLUSION: ATRA treatment suppressed UAE and TGF-beta1 synthesis, which was mediated by significant reductions in PKC activity and ROS production. Our results suggest that ATRA has a potential therapeutic role for diabetic nephropathy.
Animals ; Diabetes Mellitus, Type 2/*complications ; Diabetic Nephropathies/*complications/*drug therapy/pathology ; Mesangial Cells/*metabolism ; Oxidative Stress/drug effects ; Rats ; Rats, Inbred OLETF ; Reactive Oxygen Species/metabolism ; Transforming Growth Factor beta1/analysis/pharmacology ; Tretinoin/*pharmacology/therapeutic use

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

Berberine (BBR) is a type of alkaloids isolated from Coptidis Rhizoma and Phellodendri Chinensis Cortex and has been used to treat bacterial gastroenteritis, diarrhea and other digestive diseases for more than 1 000 years. According to recent studies, berberine has been found to have multiple pharmacological activities, including lowering blood glucose and lipid, anti-inflammation, antioxidation, relieving type 2 diabetic nephropathy (DN), diabetic cardiovascular disease, diabetic peripheral neuropathy ( DPN) and other complications. In this article, the authors summarized the literature reports about the effects of BBR in lowering blood glucose and preventing and treating the above type 2 diabetes and its complications, in order to provide reference to further studies and promotion of BBR's application.
Animals ; Berberine ; administration & dosage ; Blood Glucose ; metabolism ; Diabetes Complications ; drug therapy ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans

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

Along with the development of economy and society, type 2 diabetic mellitus (T2DM) has become one of the most common diseases at the global level. As one of the complications of T2DM, diabetic neuropathic pain (DNP) stubbornly and chronically affects the health and life of human beings. In the pain field, dorsal root ganglion (DRG) is generally considered as the first stage of the sensory pathway where the hyperexcitability of injured neurons is associated with different kinds of peripheral neuropathic pains. The abnormal electrophysiology is mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents (I(Na)). Curcumin is an active ingredient extracted from turmeric and has been demonstrated to ameliorate T2DM and its various complications including DNP effectively. The present study demonstrates that the I(Na) of small-sized DRG neurons are significantly increased with the abnormal electrophysiological characteristics of VGSCs in type 2 diabetic neuropathic pain rats. And these abnormalities can be ameliorated efficaciously by a period of treatment with curcumin.
Animals ; Curcumin ; pharmacology ; Diabetes Mellitus, Experimental ; complications ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Neuropathies ; drug therapy ; Ganglia, Spinal ; cytology ; drug effects ; metabolism ; Neuralgia ; drug therapy ; Neurons ; drug effects ; metabolism ; Rats ; Sodium ; Voltage-Gated Sodium Channels ; physiology