OBJECTIVETo study the effects of Jiaotai Pill (JTP) and its single components on ectopic fat accumulation in rats with type 2 diabetes mellitus (T2DM).

METHODSThe T2DM model of rat was established by injection of streptozotocin from tail vein and high fat-caloric diet feeding. Model rats were randomly divided into the model group and four treated groups were treated respectively with JTP and its single components, Rhizoma Coptidis, Cinnamon and metformin, via gastric perfusion. Meanwhile, a normal control group was also set up. Body weight (BW), liver index (LI), levels of fasting plasma glucose (FPG), fasting serum insulin (FINS) and insulin resistance index (HOMA-IR), plasma activities of liver associated enzymes (LAE), triglyceride (TG) contents and pathological changes of liver, heart and muscle were determined before and after a 8-week treatment.

RESULTSAs compared with the normal rats, BW, LI, LAE activities, HOMA-IR, TG contents of the liver, heart and muscle were all increased in the model rats (P<0.05 or P<0.01), with pathologic appearance of fatty degeneration in different degrees. Compared with the model group, LI, LAE, HOMA-IR, and TG contents in the liver, heart and muscle tissues were decreased in different extents in the four treated groups (P<0.05 or P<0.01), and the histology of tissues in them was restored to near normal. Compared with the metformin treated group, the hepatic and muscular TG contents decreased in the JTP treated group (P<0.01), and the muscular TG content in the Rhizoma Coptidis treated group were lower (P<0.05). And the gamma-GT level in the JTP treated group was the lowest in the three Chinese drugs treated groups (P<0.01).

CONCLUSIONSThe disturbances of glucose and lipid metabolism and abnormality of liver function in T2DM rats could be improved by JTP and its single components. The mechanism might be related to their effects in improving insulin resistance and reducing ectopic fat accumulation.

Adiposity ; drug effects ; Animals ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Insulin Resistance ; Intra-Abdominal Fat ; pathology ; Lipid Metabolism ; drug effects ; Liver ; pathology ; Male ; Muscle, Skeletal ; metabolism ; Phytotherapy ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effect of Tongshenluo Capsule (TSL) on the components of extracellular matrix (ECM) and their metabolism in kidney of rats with diabetic nephropathy (DN), and to explore its mechanism of kidney protecting.

METHODSThe DN model rats established by one side nephrectomy and intraperitoneal injection of streptozotocin were randomly divided into 5 groups, the sham-operation group, the model group, the Valsartan group, the Gliquidon group, and the TSL group, 10 in each group. Levels of fasting blood glucose (FBG) and 24-h urinary micro-content of albumin (24 h mAlb) were determined dynamically; the serum glycosyl hemoglobin (HbA1c)was determined after the last medication; the ultrastructural changes of kidney were observed by transmission electron microscope; the expressions of collagen IV (IV-C), fibronctin (FN), laminin(LN), and the ECM metabolism influencing factors, including MMP-2, tissue inhibitor of metalloproteinase (TIMP-2), transfer growth factor-beta1 (TGF-beta1) in renal tissue were detected by immunohistological chemistry and image collecting analytical system. Results TSL could decrease the levels of FBG, HbA1c, 24 h mAlb (P < 0.05 or P < 0.01), ameliorate the thickness of glomerular basement membrane (GBM), decrease the components of ECM, down-regulate TGF-beta1 and TIMP-2 expression, and up-regulate MMP-2 expression (P < 0.05 or P < 0.01).

CONCLUSIONTSL plays a role of kidney protection by decreasing the ECM components expression and regulate ECM metabolism.

Animals ; Capsules ; Collagen Type IV ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; Diabetic Nephropathies ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Extracellular Matrix ; drug effects ; metabolism ; Fibronectins ; metabolism ; Kidney ; drug effects ; metabolism ; pathology ; Laminin ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the renal protective activity of Hsian-tsao Mesona procumbens Hemsl. water extracts in diabetic rats.

METHODSThirty Sprague-dawley female rats were randomly divided into three groups (n = 10 each), "control group" with intraperitoneal saline injection, "diabetic group" with 60 mg of intraperitoneal streptozotocin injection per kg of body weight and "Hsian-tsao group" with intragastric administration of Hsian-tsao extraction everyday for 4 weeks after intraperitoneal streptozotocin injection. The body weight and blood sugar were measured before and after model induction in the three groups. Thrombospondin-1 (TSP-1) expressions in the kidney were monitored by immunohistochemistry. Kidney ultrastructural changes were also analyzed by using transmission electron microscopy.

RESULTSBefore diabetic model induction, there were no significant differences among the three groups in body weight and blood sugar. Four weeks after the induction of diabetes, the differences became statistically significant. Electron microscopy also revealed disruption of the foot processes of the podocytes and other damages in diabetic group. These damages were significantly less severe in Hsian-tsao group when compared with the diabetic group. TSP-1 expressions in the kidney were significantly increased in both the diabetic group and Hsian-tsao group, but it was relatively lower in Hsian-tsao group than in diabetic group.

CONCLUSIONOur results showed that Hsian-tsao treatment in the diabetic rats effectively prevented the pathological alterations in the kidney and decreased the TSP-1 expression. It was suggested that Hsian-tsao had protective effect on the kidneys of the diabetic rats.

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; pathology ; Diabetic Nephropathies ; metabolism ; pathology ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Kidney ; drug effects ; metabolism ; pathology ; ultrastructure ; Lamiaceae ; chemistry ; Rats ; Rats, Sprague-Dawley ; Thrombospondin 1 ; metabolism

The aim of this study is to investigate the effects of the metformin on the formation of hepatic fibrosis in type 2 diabetic rats and discuss its mechanism of liver-protecting activity. After SD rats were fed with high-fat and high-sucrose diet for four weeks, low-dose streptozotocin (STZ) was injected intraperitoneally to make the animal mode of type 2 diabetes. Then, all diabetic rats was fed with the high-fat diet and metformin (ig, 100 mg x kg(-1)) was given orally to metformin group for four months. After the last administration, fasting blood glucose was determined. The livers were removed to calculate the hepatic coefficient and to make HE and Picro acid-Sirius red staining, immunohistochemistry (alpha-SMA and TGFbeta1) and TUNEL staining in order to evaluate the effect of metformin on the hepatic fibrosis. The animal model of type 2 diabetes with hepatic fibrosis was successfully made. Metformin can significantly alleviate the lesions of hepatic steatosis and fibrosis, markedly reduce the expressions of alpha-SMA and TGFbeta1 in liver tissue of type 2 diabetic rats. However, TUNEL staining result suggested that metformin could not reduce apoptosis of hepatocytes. The results suggest that metformin can inhibit the formation of hepatic fibrosis in type 2 diabetes.
Actins ; metabolism ; Animals ; Apoptosis ; drug effects ; Blood Glucose ; metabolism ; Body Weight ; drug effects ; Diabetes Mellitus, Experimental ; drug therapy ; etiology ; metabolism ; pathology ; Diabetes Mellitus, Type 2 ; drug therapy ; etiology ; metabolism ; pathology ; Diet, High-Fat ; Female ; Hepatocytes ; pathology ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Liver ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; drug therapy ; metabolism ; pathology ; Male ; Metformin ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo investigate nephrin and desmin expression in rat podocytes in early diabetic nephropathy (DN) and the rale of angiotensin II receptor antagonist in renal protection.

METHODSRat models of DN established by a injection of a single dose of streptozotocin (STZ) were randomized into model group and irbesartan group, with rats without STZ injection as the normal control group. The rats in irbesartan group were subjected to daily intragastric irbesartan administration for 8 consecutive weeks, while those in the model group received only saline in the same manner. Upon completion of the treatment, the rats were sacrificed and pathological changes of the kidney were examined with optical and transmission electron microscope. Nephrin and desmin expressions in the podocytes were detected by immunohistochemistry.

RESULTSIn rats with DN, irbesartan administration alleviated podocyte injury and significantly lowered the expression of nephrin and desmin (P<0.05).

CONCLUSIONAngiotensin II receptor antagonist may offer renal protection against DN by alleviating structural and functional podocyte damage through decreasing nephrin expression in the podocytes.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Biphenyl Compounds ; therapeutic use ; Desmin ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetic Nephropathies ; drug therapy ; Kidney ; pathology ; Membrane Proteins ; metabolism ; Podocytes ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Tetrazoles ; therapeutic use

OBJECTIVETo investigate the effects of icariin on cardiac functions and mitochondrial oxidative stress in streptozotocin (STZ)-induced diabetic rats.

METHODMale SD rats were randomly divided into normal control group, icariin control group, diabetic group, and diabetic groups administered with a low dose (30 mL x kg(-1) x d(-1), ig) or a high dose (120 mL x kg(-1) d(-1), ig) of icariin for 8 weeks. The body weight, blood glucose, cardiac functions, left ventricular weight, and myocardial collagen level were assayed. The cardiac mitochondrial reactive oxygen species (ROS) level, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity were measured.

RESULTTreatment with icariin reduced the losing of body weight in diabetic rats. Icariin markedly reduced the ratio of ventricular weight and body weight, increased the left ventricular develop pressure and +/- dp/dt(max), and decreased the left ventricular end diastolic pressure in diabetic rats. The myocardial collagen and the level of cardiac mitochondrial ROS in diabetic rats were all markedly reduced by icariin. Furthermore, high dose of icariin significantly decreased the mitochondrial MDA level and increased SOD activity in diabetic rat hearts.

CONCLUSIONTreatment with icariin for 8 weeks markedly improved the cardiac function, which may be related to reducing mitochondrial oxidative stress injuries in diabetic rats.

Animals ; Body Weight ; drug effects ; Collagen ; drug effects ; metabolism ; Diabetes Mellitus, Experimental ; chemically induced ; drug therapy ; metabolism ; pathology ; Diabetes Mellitus, Type 1 ; drug therapy ; metabolism ; pathology ; Diabetic Cardiomyopathies ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; Enteral Nutrition ; Flavonoids ; administration & dosage ; Heart Ventricles ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Mitochondria, Heart ; drug effects ; metabolism ; pathology ; Organ Size ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Streptozocin ; Superoxide Dismutase ; drug effects ; metabolism

AIMTo study the protective effect of Gingko biloba extract (EGb) against myocardial impairment in diabetic rats.

METHODSMorphology of effect of EGb on myocardium in diabetic rats was observed under light microscopy (LM) and transmission electron microscopy (TEM). Activity of super oxide dismutase (SOD), nitric oxide synthase (NOS), constitutive nitric oxide synthase (cNOS), inductive nitric oxide synthase (iNOS) and content of malondialdehyde (MDA), nitric oxide (NO) were detected biochemically in myocardial homogenate.

RESULTSIt was manifestation as vascular degeneration and local lysis of myocardial fiber under LM and swelling of mitochondria, shorten of mitochondrial crest, lysis of myofibril under TEM, the activity of SOD decreased and the activity of NOS, iNOS, the content of NO, MDA increased, but the morphological changes became slight in EGb treatment group. Activity of SOD increased while activity of NOS, iNOS and content of MDA, NO decreased in EGb treatment group compared with diabetic group.

CONCLUSIONEGb can protect diabetic myocardium and anti-lipid peroxidation and decrease of NO level may be involved in it.

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; pathology ; Ginkgo biloba ; Lipid Peroxidation ; drug effects ; Male ; Myocardium ; metabolism ; pathology ; Nitric Oxide Synthase ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the mechanism of Shenkangwan (SKW) in treating early diabetic nephropathy (DN).

METHODSThe effect of SKW on NO and transforming growth factor (TGF)-beta(1) production by the mesangial cells (MCs) of rats with early diabetic nephropathy was evaluated with serum pharmacological method.

RESULTSCompared with normal serum, the SKW-containing serum dose- and time-dependently inhibited TGF-beta(1) excretion and increased NO production in the MCs of rats with early DN (P<0.05 and P<0.01, respectively).

CONCLUSIONThe therapeutic effect of SKW on early DN may rely on the balance modulation of cytokine network by increasing NO production and decreasing TGF-beta(1) excretion to prevent cytokine-induced damage of the MCs.

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Diabetic Nephropathies ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Glomerular Mesangium ; metabolism ; pathology ; Male ; Nitric Oxide ; biosynthesis ; Rats ; Rats, Wistar ; Transforming Growth Factor beta ; biosynthesis

OBJECTIVETo study the effect of Shengji Huayu Recipe (SHR)on the expression of MMP-3 and TIMP-1 in the skin ulcer tissue of diabetic rats.

METHODSThe skin ulcer model was established in diabetic mice. Different compatibility proportions of SHR [the ratio of Shengji Recipe (SJR) to Huayu Recipe (HYR) = 2:1, 1:1, and 1:2, respectively] were used to intervene. The expression of MMP-3 protein in the skin ulcer of diabetic rats was detected by Western blot method,and TIMP-1 protein was detected by immunohistochemical assay.

RESULTSAt each time point, there was no statistical difference in the blood glucose level among groups (P > 0.05). But all of them increased significantly,when compared with those of the normal wound group (P < 0.01). As for the difference between after would area treatment and before would area treatment, better effect was obtained in the SHR No. 3 group and the normal ulcer group than in the diabetic ulcer model group (P < 0.05). Results of Western blot showed that the MMP-3 protein expression was higher in the SHR No. 2 group than in the SHR No.3 group (P < 0.05). Immunohistochemical results showed that TIMP-1 protein expression was lower in the SHR No. 2 group than in the SHR No. 3 group and the diabetic ulcer model group (P < 0.05). TIMP-1 protein expression was higherin the SHR No. 3 group than in the SHR No. 2 group (P < 0.01).

CONCLUSIONUsing SHR No.3 was conducive to the promotion of wound healing in early wound repair stage, and using SHR No. 2 might be conducive to inhibiting the formation of pathological scar.

Animals ; Diabetes Mellitus, Experimental ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Matrix Metalloproteinase 3 ; metabolism ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; pathology ; Skin Ulcer ; drug therapy ; metabolism ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism

OBJECTIVETo study the possible pathogenic mechanism of liver injury in type 2 diabetes mellitus (T2DM) and the intervening effect of puerarin on it.

METHODSMice with T2DM (KKAy) were randomly divided into two groups, the model group and the puerarin group. And the C57BL/J mice of the same age were set up as normal controls. They were sacrificed at 28 weeks old for observing serum fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST) by automatic biochemistry; liver cell apoptosis by flow cytometry; pathomorphology by electron microscope; and mRNA expressions of bcl-2 and bax genes by RT-PCR; as well as the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Na(+)-K(+)-ATPase; and content of malondialdehyde (MDA) in liver tissue by spectrophotometer.

RESULTSIn KKAy mice, blood levels of FBG, TG, TC, ALT, AST and liver cell apoptosis rate were higher; the bax mRNA expression was higher and bcl-2 mRNA was lower markedly; the activities of SOD, GSH-Px, Na(+)-K(+)-ATPase in liver tissue were lower, and MDA content was higher than those in the normal control significantly (all P <0.01). Besides, mitochondria swelling and damage were found in liver tissue. While in the puerarin group after treatment, all the above-mentioned changes were alleviated to some extent.

CONCLUSIONSObvious liver injury emerges in KKAy mice. Puerarin shows a protective effect on the T2DM caused oxidative damage by way of up-regulating bcl-2 to inhibit oxidative stress, and improving the energy metabolic dysfunction in liver of mice.

Animals ; Diabetes Mellitus, Experimental ; complications ; drug therapy ; pathology ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; pathology ; Isoflavones ; therapeutic use ; Liver ; metabolism ; physiopathology ; Liver Diseases ; drug therapy ; etiology ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria, Liver ; pathology ; Oxidative Stress ; Phytotherapy ; Proto-Oncogene Proteins ; metabolism ; Proto-Oncogene Proteins c-bcl-2