OBJECTIVETo elucidate the volume changes of cortical and subcortical reward circuitry in patients with type 2 diabetes mellitus.

METHODSHigh-resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MRI images were obtained from 16 patients with type 2 diabetes mellitus and 16 normal controls, and 11 type 2 diabetic patients also received the same MRI scans after insulin therapy for 1 year. Volumetric analysis was performed and analysis of covariance and paired t test were applied.

RESULTSA decreased volume was found in the left insular lobe, left nucleus accumbens area, right hippocampus, putamen and amygdala in type 2 diabetic patients compared with normal controls (P<0.05). After insulin therapy for 1 year, an increased volume of bilateral cortical reward structures was observed (left, 33.65∓3.66 ml; right, 33.35∓4.25 ml) compared the baseline level (left, 31.45∓2.90 ml; right, 31.12∓2.97 ml) in diabetic patients (P<0.05). No significant volume change in the bilateral basal ganglia structures was found after insulin therapy for 1 year (P>0.05), and bilateral ventral diencephalon area showed an increased volume after the treatment (left, 3.26∓0.68 ml; right, 3.20∓0.78 ml) compared with the baseline (left, 2.96∓0.76 ml; right, 2.82∓0.90 ml)(P<0.05).

CONCLUSIONType 2 diabetic patients have a decreased volume of the cortical and subcortical reward circuitry, and insulin therapy can reverse such changes and improve the damage of reward circuitry.

Aged ; Cerebral Cortex ; pathology ; Diabetes Mellitus, Type 2 ; drug therapy ; pathology ; Entorhinal Cortex ; pathology ; Female ; Humans ; Insulin ; therapeutic use ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Nucleus Accumbens ; pathology

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

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Ginkgo biloba ; chemistry ; Liver ; pathology ; Liver Cirrhosis ; drug therapy ; Male ; Phytotherapy ; Plant Extracts ; therapeutic use ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effects of Meilian Xiaoke capsule (a traditional Chinese medicinal preparation) combined with metformin for protecting islet cells and lowering blood glucose in diabetic rats.

METHODSRat models with type 2 diabetes, established by high-fat and high-glucose diet combined with streptozotocin (STZ) injection, were treated with a low dose of metformin, Meilian Xiaoke capsule, or both for 4 weeks by gavage. Blood glucose level was tested in the rats, and islet pathologies and changes in islet β cell number after the treatment were observed with HE staining and aldehyde fuchsin staining, respectively.

RESULTSTreatment with metformin or Meilian Xiaoke capsule alone for 2 or 4 weeks did not produce significant improvement of blood glucose in the diabetic rats. Their combined treatment for 4 weeks resulted in significantly lowered blood glucose level and improved glucose tolerance with also obviously increased islet β cell number and lessened islet pathologies.

CONCLUSIONSMeilian Xiaoke capsule and metformin show a synergistic effect to significantly enhance the therapeutic effect in rats with type 2 diabetes.

Animals ; Blood Glucose ; drug effects ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Drug Synergism ; Drugs, Chinese Herbal ; pharmacology ; Hypoglycemic Agents ; pharmacology ; Insulin-Secreting Cells ; pathology ; Metformin ; pharmacology ; Rats ; Streptozocin

BACKGROUNDIntensive insulin therapy has been found to lessen the progress of diabetic retinopathy (DR) to some extent, while it has also been implicated to be responsible for decrease of DR. We investigated visual function and morphological changes in the macular area in short-term follow-up of patients with type 2 diabetes mellitus after intensive insulin therapy.

METHODSThis was a prospective clinical study of nonproliferative DR patients (102 eyes, 120 patients) undergoing intensive insulin therapy. The Contrast Glare Tester (Takagi CGT-1000) was used to examine contrast sensitivity (CS) and Heidelberg Retina Tomograph (HRT) II and Stratus Model 3000 OCT were used to observe the changes of morphology in the macular area. Follow-up times were pre-intensive therapy, 3 and 6 months post-intensive therapy.

RESULTSCS at low and middle frequencies was higher at 3 and 6 months post-therapy compared with pre-therapy (P < 0.05). Significant differences in CS at low frequency were found between 6 and 3 months post-therapy (P < 0.05). Macular edema index was lower in the first, second, and third rings of the macular area after intensive therapy compared with pre-therapy (P < 0.05). Compared with 3 months post-therapy, the macular edema index was lower in the first, second, and third rings of the macular area at 6 months post-therapy (P > 0.05). No significant differences in the thickness of the first, second, and third rings of the macular area were detected between 3 and 6 months post-therapy and pre-therapy (P > 0.05).

CONCLUSIONCS and macular edema indexes were significantly improved in nonproliferative diabetic retinopathy patients after intensive insulin therapy, but thickness of the macular area was unchanged.

Diabetes Mellitus, Type 2 ; drug therapy ; pathology ; physiopathology ; Follow-Up Studies ; Humans ; Insulin ; therapeutic use ; Macula Lutea ; pathology ; Middle Aged ; Prospective Studies ; Tomography, Optical Coherence ; Vision, Ocular ; physiology

OBJECTIVETo study the effects of Liuweidihuang pills on pancreatic islet structure in OLETF (Otsuka Long-Evans Tokushima Fatty) rats.

METHODSForty male OLETF rats were divided randomly into Liuweidihuang pills group (Liuwei group) and control group (n=20). Ten male LETO rats were used as normal control group (LETO group). The rats in Liuwei group were given Liuweidihuang pills at the daily dose of 2.4 mg/kg intragastrically since the age of 8 weeks. Blood glucose was determined by OGTT. The rats were sacrificed at 8, 32 and 40 weeks and the pancreatic tissue was isolated to examine the morphological changes of the pancreas by HE staining and Masson trichrome staining.

RESULTSAs the age of the rats increased, the pancreatic islets in the control group gradually showed fibrosis and islet atrophy, which were not found in Liuwei group. Masson staining visualized no fibrosis in Liuwei group. No significant pathological change occurred in the pancreatic islet of LETO rats. The rats in Liuwei group developed diabetes since 30 weeks of age and the incidence was 28.6% at 40 weeks, significantly lower than that in the control group (P<0.01).

CONCLUSIONLiuweidihuang pills can prevent degeneration of the pancreatic islets in spontaneous OLETF rats.

Animals ; Diabetes Mellitus, Type 2 ; drug therapy ; pathology ; Drugs, Chinese Herbal ; therapeutic use ; Islets of Langerhans ; pathology ; Male ; Phytotherapy ; Protective Agents ; therapeutic use ; Random Allocation ; Rats ; Rats, Inbred OLETF

BACKGROUNDControlling plasma glucose levels, blood pressure and lipid levels is proven to reduce the risk of vascular complications in patients with type 2 diabetes mellitus. This has prompted intensive multitherapy targeted at several macrovascular risk factors. Carotid intima-media thickness (cIMT) is a reliable measure of early atherosclerosis. We sought to determine whether a 6-month intensive mutiltherapy program resulted in better goal attainment than usual care and its effect on the development of cIMT among patients with newly diagnosed type 2 diabetes mellitus.

METHODSThe study randomly assigned 220 patients with newly diagnosed type 2 diabetes mellitus to intensive or traditional therapy groups. The clinical parameters, such as fasting plasma glucose, total cholesterol, triglyceride, blood pressure, body weight and insulin were assessed at the baseline and after the 6-month therapy. cIMT of the patients was also obtained.

RESULTSThe average levels of fasting plasma glucose, hemoglobin A1c, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the intensive group were significantly lower than those in the control group at the end of 6-month treatment. By 6 months, a higher proportion of patients in the intensive therapy group than in the control group attained goals for fasting plasma glucose (FPG), TC, LDL-C and hemoglobin A1c. With intensive multherapy the level of carotid intima-media thickness in the intensive therapy group was lower than that in the control group ((0.88 +/- 0.26) mm vs (0.96 +/- 0.22) mm, P < 0.01).

CONCLUSIONSThe evidence from this clinical trial demonstrates that intensive glucose, lipid and blood pressure control in patients with newly diagnosed type 2 diabetes is associated with diabetic macrovascular benefits. Intensive multitherapy allows more patients to achieve aims of control and may reduce macrovascular complications and delay disease progression.

Arteriosclerosis ; prevention & control ; Carotid Arteries ; pathology ; Diabetes Complications ; prevention & control ; Diabetes Mellitus, Type 2 ; drug therapy ; Drug Therapy, Combination ; Humans ; Hypoglycemic Agents ; administration & dosage ; Middle Aged ; Prospective Studies ; Tunica Intima ; pathology

OBJECTIVETo study the effect of total saponins from Entada phaseoloides (TSEP) on islet morphology and skeletal muscle PI3K pathway-related protein expression of type 2 diabetic rats.

METHODType 2 diabetic rats were induced by high-fat diet and low-dose streptozotocin and then randomly divided into 5 groups, i.e. the normal control, the model group, the positive control drug (200 mg x kg(-1) metformin), the low-dose TSEP (25 mg x kg(-1)) group and the high-dose TSEP (50 mg x kg(-1)). Three weeks later, the islet morphology of rat pancreas were observed by HE staining, and protein expressions of insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), protein tyrosine phosphatase-1B (PTP-1 B) and glucose transporter 4 (GLUT4) in rat skeletal muscle were detected by Western blot.

RESULTCompared with the modal group, TSEP administration groups showed relatively normal structures, clear pancreatic cells and intact capsula structures in pancreatic tissue pathological sections, with the number of pancreatic islets close to the normal control group. Meanwhile, above TSEP administration groups showed increased IRS-1, PI3K and GLUT4 protein expressions in their skeletal muscle tissues and decreased PTP-1B protein expression compared with the model group.

CONCLUSIONTSEP has an effect on protecting pancreatic tissues of type 2 diabetic rats and intervening in abnormal expression of proteins in skeletal muscle tissues.

Animals ; Diabetes Mellitus, Type 2 ; drug therapy ; Fabaceae ; chemistry ; Glucose Transporter Type 4 ; analysis ; Islets of Langerhans ; drug effects ; pathology ; Male ; Muscle, Skeletal ; drug effects ; pathology ; Phosphatidylinositol 3-Kinases ; analysis ; Rats ; Rats, Sprague-Dawley ; Saponins ; therapeutic use

This study aimed to investigate the therapeutical effects of Rhodiola rosea extract on rats with type 2 diabetic nephropathy (DN). The rat type 2 DN model was established by high fat and high calorie feeding and intravenous injection of streptozocin (STZ). Wistar rats were randomly divided into normal group, control group, low dose Rhodiola rosea group, high dose Rhodiola rosea group and Captopril group. Oral glucose tolerance test (OGTT) was performed to determine the impairment of glucose tolerance in the established animal model. A series of parameters including fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), creatinine clearance rate (Ccr), 24-h urinary albumin (UA), the ratio of kidney mass/body weight (renal index) and glomerular area were examined after 8 weeks. Moreover, the expression of transforming growth factor (TGF)-β1 in renal tissues was detected by using immunohistochemisty. At the end of the eighth week, FBG, TC, TG, Ccr, 24-h urinary albumin, the ratio of kidney mass/body weight and glomerular area were significantly reduced in Rhodiola rosea extract treatment groups as compared with those in control group. TGF-β1 expression in renal tissues of Rhodiola rosea extract treatment groups was also significantly decreased as compared with that of control group. These results indicate that Rhodiola rosea extract may have a protective effect on early nephropathy in diabetic rats, which might be related to the decrease of the renal expression of TGF-β1.
Animals ; Diabetes Mellitus, Type 2 ; drug therapy ; pathology ; physiopathology ; Diabetic Nephropathies ; drug therapy ; pathology ; physiopathology ; Drugs, Chinese Herbal ; administration & dosage ; Ethanol ; chemistry ; Glomerular Filtration Rate ; drug effects ; Male ; Plant Extracts ; administration & dosage ; chemistry ; Rats ; Rats, Wistar ; Rhodiola ; chemistry ; Treatment Outcome

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