Effect of curcumin derivative B06 on liver from type 2 diabetic rats

AIM:To observe the protective effect of curcumin derivative B06 on the liver from the rats with hyperlipidemia and type 2 diabetes mellitus. METHODS:Male Sprague-Dawley rats (n=35) were divided randomly into 5 groups: normal control group, high-fat group, high-fat+B06-treated group, diabetic group and diabetic +B06-treated group. After fed with a high-fat diet for 4 weeks, the rats in the later 2 groups were injected with streptozotocin intraperitoneally to induce type 2 diabetes mellitus. The rats in B06-treated groups were given B06 by gavage at a dose of 0.2 mg· kg-1·d-1 for 8 weeks. After the treatment, the morphology of the liver was observed under light and transmission electron microscopes. The protein expression of AMP-activated protein kinase α (AMPKα) and phosphorylated AMPK α (p-AMPKα) was detected by Western blotting. RESULTS:Fatty degeneration, hepatocellular necrosis, inflammatory cell infiltration and hyperplasia of fibrous tissue were observed in the liver from the rats in high-fat group and diabetic group,and were relieved after B06 treatment. The protein expression of p-AMPKα was decreased in the liver of the rats in diabetic group and high-fat group, and it was increased in the liver of the high-fat and diabetic rats in B06-treated group. CONCLUSION:Curcumin derivative B06 exerts a protective effect on the liver in type 2 diabetic rats, and the increased expression of p-AMPKα may be involved in the mechanism of protection.     

Protective effects of sequoyitol on type 2 diabetic rats with liver inflammatory lesions

AIM：To investigate the possible protective effect of sequoyitol on type 2 diabetic rats with liver inflammatory lesions. METHODS：Type 2 diabetic rats were induced by feeding high-fat/high-sugar diet and injecting with a low dose of streptozotocin. Sequoyitol at doses of 12.5, 25 and 50 mg·kg-1·d-1 was orally administered in the model rats. At the end of the experiment, the rats were sacrificed. Serum levels of fasting blood glucose, alanine aminotransferase(ALT), aspartate aminotransferase(AST) and albumin(ALB) were determined. Liver wet was recorded and liver index was calculated. The levels of C-reactive protein(CRP),tumor necrosis factor α(TNF-α) and interleukin 6(IL-6) in the liver tissues were also measured. Real-time PCR was used to determine the mRNA expression of TNF-α. In addition, the pathological changes of the liver were observed with HE staining. RESULTS：Compared with the model rats, treatment with sequoyitol obviously decreased the levels of fasting blood glucose, ALT, AST, ALB, CRP, TNF-α and IL-6, reduced the liver index, down-regulated the mRNA expression of TNF-α in the liver, and ameliorated the pathologic changes of the liver. CONCLUSION：Sequoyitol attenuates liver lesions in type 2 diabetic rats through down-regulation of TNF-α and IL-6 expression.     

Effect of gingko biloba extract on liver from experimental type 2 diabetic rats

AIM:To study the protective effect of the ginkgo biloba (EGB) extract on liver from experimental type 2 diabetic rats and to explore its possible mechanism. METHODS:Thirty-nine male Sprague-Dawley rats were divided randomly into four groups: normal control group, high-fat group, diabetic group and EGB-treated group. After fed with high-fat diet for 4 weeks, the later two groups were injected with streptozotocin intraperitoneally to induce type 2 diabetes mellitus. EGB-treated group was injected intraperitoneally with EGB at a dose of 8 mg·kg^-1·d^-1, and the other three groups were treated with normal saline of the same volume. After 8 weeks, the morphologic change of hepatic tissue was observed under transmission electron microscope (TEM) and light microscope (LM), respectively. In addition, the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), total nitric oxide synthase (TNOS), inducable nitric oxide synthase (iNOS) and the content of malondialdehyde (MDA), nitric oxide (NO) in liver homogenate were detected biochemically. RESULTS:Obvious liver fatty degeneration, apparent decrease of glycogen granules in cytoplasm of hepatocytes under light microscope and hepatocytes pyknosis, lots of lipid deposits in cytoplasm of hepatocytes, proliferation of hepatic stellate cells and collagen under TEM were observed in diabetic group. The activity of SOD, CAT, GSH-PX decreased but the activity of tNOS, iNOS and the content of MDA, NO^-₂/NO^-₃ increased in diabetic group compared with normal control group. The pathological change was relieved in EGB-treated group. The activity of SOD, CAT, GSH-PX increased, the activity of tNOS, iNOS and the content of MDA, NO^-₂/NO^-₃ decreased in the liver of rats in EGB-treated group compared with diabetic group. CONCLUSION:EGB exerts a beneficial effect on liver in experimental type 2 diabetic rats. Anti-lipid peroxidation and suppression of NO production may be involved in this process.     

Liraglutide ameliorates liver injury of type 2 diabetic mice via micro-RNA-33-AMPK pathway

AIM: To observe the effects of liraglutide on the level of microRNA-33 (miR-33) and the expression of AMP-activated protein kinase (AMPK) and apoptosis-related proteins in mice with type 2 diabetes mellitus (T2DM), and to explore its possible mechanism. METHODS: High-fat diet and intraperitoneal injection of streptozocin were used to establish the type 2 diabetic model in C57BL/6 mice. The mice were randomly divided into 4 groups (n=15):in control group, the normal mice were subcutaneously injected with equivalent volume of saline; in model group, the T2DM mice were subcutaneously injected with equivalent volume of saline; in low-and high-dose liraglutide treatment groups, the T2DM mice were subcutaneously injected with 100 and 200 μg·kg^-1·d^-1, respectively. After 4 weeks of administration, the levels of FBG, TG, TC, HDL-C, LDL-C, ALT and AST were determined. HE staining was used to observe the pathological changes of the liver tissues. The protein level of cleaved caspase-3 in the liver tissue was detected by the technique of immunofluorescence. The protein levels of p-AMPK/AMPK and apoptosis-related proteins were detected by Western blot. The expression of miR-33 in the liver tissues was detected by real-time PCR. RESULTS: Compared with model group, the contents of FBG, TG, TC, LDL-C, ALT and AST were decreased significantly, while the content of HDL-C was increased significantly in low-dose liraglutide group and high-dose liraglutide group (P<0.05). The protein levels of phosphorylated AMPK and Bcl-2 were up-regulated significantly, and the expression of cleaved caspase-3 was down-regulated significantly (P<0.05). The level of miR-33 was decreased significantly (P<0.01). CONCLUSION: Liraglutide alleviates liver injury in type 2 diabetic mice, and the mechanism may be associated with reducing the level of miR-33 and increasing the phosphorylation of AMPK in the liver tissues, thereby inhibiting hepatocyte apoptosis.     

Effects of puerarin combined with saxagliptin on renal fibrosis in type 2 diabetic rats

AIM：To observe the effects of puerarin combined with saxagliptin on renal fibrosis in type 2 diabetic rats. METHODS：Fifty male Wistar rats were used, of which 8 rats were randomly chosen as normal control group, and the remaining rats were used to establish the type 2 diabetic model. The rats that met the criterion for the diabetic mo-del were randomly divided into model group, puerarin treatment group, saxagliptin treatment group, puerarin combined with saxagliptin treatment group and metformin combined with saxagliptin treatment group. The above-mentioned drugs were administered for 8 weeks. After that period, all rats were sacrificed. The kidney index (kidney weight/body weight),and blood glucose and HbA1c were examined in all the rats. The morphological changes were observed by HE and Masson staining. The levels of TNF-α and macrophage migration inhibitory factor (MIF) in the serum were measured by ELISA. The mRNA expression of TNF-α, MIF and CD68 was examined by RT-PCR. RESULTS：Compared with normal group, the kidney index, blood glucose and HbA1c, the levels of TNF-α and MIF in the serum and the mRNA expression of TNF-α, MIF and CD68 were increased (P<0.05) in the kidney tissues of model group. Compared with model group, the kidney index, blood glucose and HbA1c, the levels of MIF and TNF-α in the serum and the mRNA expression of TNF-α, MIF and CD68 were decreased (P<0.05) in puerarin combined with saxagliptin treatment group. CONCLUSION：Puerarin combined with saxagliptin reduces blood glucose, decreases MIF and TNF-α, and down-regulates the mRNA expression of TNF-α, MIF and CD68 in the kidney tissues of type 2 diabetic rats, which may contribute to the inhibition of renal fibrosis.     

Effect of non-alcoholic fatty liver disease on metabolic syndrome-rela-ted type 2 diabetes

AIM: To investigate the effect of non-alcoholic fatty liver disease (NAFLD) on metabolic syndrome (MS)- related type 2 diabetes. METHODS: Sixty-four rats were randomly divided into 8 groups: normal control groups of 3 months (3NC), 6 months (6NC), 9 months (9NC) and 12 months (12NC), and high-sucrose and high-fat groups of 3 months (3H), 6 months (6H), 9 months (9H) and 12 months (12H). The serum levels of alanine transaminase (ALT), free fatty acid (FFA), endotoxin (LPS), tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), fasting plasma glucose (FPG) and fasting plasma insulin (FINS) were measured. The insulin resistance index (HOMA-IR) and beta cell function index(HOMA-β) were also calculated. The specimens of liver and pancreas were prepared for microscopic observation with HE and Sudan Ⅳ staining. The visceral adipose specimens were also prepared with HE staining. The apoptosis of islet cells was detected by TUNEL.RESULTS: Compared with normal control groups, the levels of ALT, FFA, LPS, TNFα, CRP, MCP-1, FPG, FINS and HOMA-IR in high-sucrose and high-fat groups of every phase were higher, but the level of HOMA-β in 6H group showed a compensatory increase first and then progressively decreased. Compared with normal control groups, TUNEL results showed that the number of apoptotic islet cells in high-sucrose and high-fat groups gradually increased from the 3rd to the 12th month. CONCLUSION: The NAFLD plays a trigger role in the start of MS-related type 2 diabetes.     

Effect of endoplasmic reticulum stress protein BiP on type 2 diabetic neuropathic pain in rats treated with curcumin

AIM: To investigate the effects of immunoglobulin heavy chain-binding protein (BiP),an endoplasmic reticulum stress protein, on mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), spinal dorsal horn and dorsal root ganglion (DRG) in type Ⅱ diabetic neuropathic pain rats treated with curcumin. METHODS: The rats were fed with a high-fat and high-fructose diet for 8 weeks to induce insulin resistance, and then were intraperitoneally injected with streptozotocin (STZ, 35 mg/kg). Eighty-one rats were selected into experimental design as their blood glucose ≥ 16.7 mmol/L 3 d after STZ injection and their MWT and TWL were decreased to 85% of the baseline values 14 d after STZ injection. The rats were divided into 3 groups (n=27 each): DNP group: type 2 diabetic neuropathic pain; DCur group: type 2 diabetic neuropathic pain and intraperitonal injection of curcumin at a dose of 100 mg·kg^-1·d^-1; DSC group: type 2 diabetic neuropathic pain and intraperitonal injection of corn oil at a dose of 4 mL/kg. Another 27 normal SD male rats fed with normal forage were adopted as control group (C group). MWT and TWL were measured at the time points of 3 d, 7 d and 14 d after curcumin injection. The lumbar segment 4~6 of the spinal cord and the corresponding DRG were removed at the same time. The expression of BiP was determined by immunohistochemical staining and Western blotting. RESULTS: Compared with C group, the rats in DNP group developed hyperglycemia and a decrease in MWT and TWL, as well as an increase in the activity of BiP in spinal dorsal horn and DRG (P<0.05). Compared with DNP group, the rats in DCur group at the time point of 7 d significantly attenuated mechanical allodynia and thermal hyperalgesia, and these effects were correlated with the inhibition of BiP hyper-activation at the time point of 14 d after treatment with curcumin (P<0.05). No significant difference of MWT, TWL and the expression of BiP between DNP group and SC group was observed. CONCLUSION: BiP participates in the pathogenesis of type Ⅱ diabetic neuropathic pain. Curcumin attenuates the MWT and TWL in type 2 diabetic neuropathic pain rats. The mechanism may be involved in the inhibition of BiP expression by curcumin.     

Influence of metformin on LPIN1 expression and AMPK signaling in high-fat diet-induced insulin resistant rats

AIM: To explore the regulatory mechanism of LPIN1 in hepatic insulin resistance by investigating the influence of metformin on the expression of LPIN1 and AMP-activated protein kinase(AMPK) signaling in the rats with high-fat diet-induced insulin resistance. METHODS: Thirty-six 4-week-old male Wistar rats were randomly divided into 2 groups: control group and high-fat diet (HF) group. The rats in HF group were fed with high-fat diet for 8 weeks and then were randomly divided into 2 subgroups: HF group and metformin intervention group, and the animals were continuously raised for 8 months. The mRNA levels of α1 and α2 subunit of AMPK as well as LPIN1 were measured by real-time RT-PCR. Phospho-AMPKα (Thr-172) was detected by Western blotting to evaluate the activity of AMPK. RESULTS: After 4 months, the rats in HF group showed significant increase in the levels of body weight, fast plasma glucose and insulin, and the levels of triglyceride and total cholesterol significantly elevated.Significant decrease in LPIN1 and phospho-AMPKα (Thr-172) expression in the rat livers were also observed. After treated with metformin, the metabolic indexes of the HF rats were improved. The mRNA and protein expression of AMPKα1 and AMPKα2 had no significant difference among the 3 groups. Metformin treatment also increased the expression of LPIN1 in the liver tissues of HF rats. CONCLUSION: The decrease in LPIN1 expression and AMPK activity may contribute to hepatic insulin resistance in diet-induced obese rats. Metformin improves the LPIN1 expression and AMPK activity through the interaction between LPIN1 and AMPK signal pathways.     

Serum levels of inflammatory factors and adiponectin in type 2 diabetic retinopathy patients

AIM: To investigate the serum levels of inflammatory factors and adiponectin in type 2 diabetic retinopathy (DR) patients.METHODS: One hundred and ten cases of type 2 diabetic patients were divided into 3 groups: no diabetic retinopathy group (DM, n=35), non-proliferative diabetic retinopathy group (NPDR, n=45), and proliferative diabetic retinopathy group (PDR, n=30). Other 40 normal persons served as controls (NC group). The physical examinated was performed for each patient. Serum levels of fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), 2 h postprandial plasma glucose (2hPG), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), adiponectin, intercellular adhesion molecule-1(ICAM-1), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP) were measured. Insulin resistance index (HOMA-IR) was also calculated.RESULTS: The systolic blood pressure, body-mass index, waist-hip ratio, serum levels of TG, LDL-C, FPG, 2hPG, HbA1c, ICAM-1, TNF-α, hs-CRP and HOMA-IR were significantly higher in DM group, NPDR group and PDR group than those in NC group (P<0.05). The systolic blood pressure, serum levels of ICAM-1, TNF-α, hs-CRP and HOMA-IR were higher in NPDR group and PDR group than those in DM group (P<0.05). The serum concentration of adiponectin was lower in DM group, NPDR group and PDR group than that in NC group (P<0.05), and that was also lower in NPDR group and PDR group than that in DM group (P<0.05). The negative correlations between adiponectin and ICAM-1 (r=-0.735,P<0.01), TNF-α (r=-0.781,P<0.01), hs-CRP (r=-0.768, P<0.01) or HOMA-IR (r=-0.752, P<0.01) were observed. The relationships between HOMA-IR and ICAM-1 (r=0.857,P<0.01), TNF-α (r=-0.906, P<0.01) or hs-CRP (r=-0.888,P<0.01) were positive.CONCLUSION: The results suggest that inflammatory refactors and adiponectin play important roles in the pathophysiology and progression of DR. The protective effects of adiponectin on DR may be related with its anti-inflammatory reactions to improve insulin resistant.     

Hypolipemic and hypoglycemic effects of total triterpenoids from Psidium guajava leaves on type 2 diabetic rats

AIM: To investigate the effects of total triterpenoids from Psidium guajava leaves (TTPGL) on blood glucose and lipids in type 2 diabetic rats. METHODS: The diabetic rats were induced by intraperitoneal injection of streptozotocin at dose of 35 mg/kg and feeding with high-fat diet. The animals were divided into 5 groups: diabetic model control group (model), TTPGL treatment groups (with the doses of 60, 120 and 240 mg/kg, respectively) and rosiglitazone treatment group (3 mg/kg). Another 12 normal SD rats were used as the normal controls. The rats received daily treatment for 6 weeks, and then the levels of fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TCH), free fatty acid (FFA), glycosylated hemoglobin (GHb) and glycosylated serum proteins (GSP) were measured. The protein expression of peroxisome proliferator-activated receptor γ (PPARγ) in adipose tissues was detected by Western blotting. RESULTS: Compared with normal control group, the levels of FBG, GHb and blood lipids were increased in type 2 diabetic rats. The FINS, insulin sensitivity index, and the protein expression of PPARγ in adipose tissues were decreased. Compared with model group, the levels of FBG and GSP were decreased,and the FINS, insulin sensitivity index, and the protein expression of PPARγ in adipose tissues significantly increased in TTPGL treatment groups (with the doses of 120 and 240 mg/kg). The levels of serum TG,TCH and FFA were significantly lower in TTPGL treatment groups (P<0.01 or P<0.05) as compared with the model controls. CONCLUSION: TTPGL decreases the levels of blood glucose and lipids in diabetic rats. TTPGL also increases serum insulin level and improves insulin sensitivity. The action mechanism of TTPGL may be related to the increase in the protein expression of PPARγ.     

Effect of curcumin derivative B06 Bob on synthesis of testosterone from type 2 diabetic rats

AIM: To investigate the effect of curcumin derivatives B06(B06) on the synthesis of testosterone from type 2 diabetic rats. METHODS: Male Sprague-Dawley rats were evenly divided into 5 groups randomly: normal control group (C group), high fat group (H group), high fat treatment group (HT group), diabetes mellitus group (D group) and diabetes treatment group (DT group). The rats in the later 4 groups were fed with high fat diet, after 4 weeks of high fat diet feeding, the rats from D group and DT group were injected with low dose of streptozotocin intraperitoneally to induce diabetes mellitus, while the rats in HT group and DT group were gavaged with B06 at the dose of 0.2 mg·kg^-1·d^-1 for 8 weeks. The blood glucose was detected by glucometer, blood insulin was assayed by ELISA and the insulin resistance index was calculated. The morphology of testes were observed by light and transmission electron microscopy. Serum testosterone and estradiol were measured by radioimmunoassay. The protein expression of steroidogenic acute regulatory protein (StAR) was detected by immunohistochemistry. The mRNA expression of StAR, cholesterol side-chain cleavage enzyme (P450scc), cytochrome P450 17A1 (P450c17), cytochrome P450 aromatizing enzyme (P450arom), 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD was detected by RT-PCR. RESULTS: The levels of blood glucose and insulin resistance index were increased in H group and D group, and serum testosterone was decreased, all of which were reversed after the treatment of B06. Testicular seminiferous tubule was distorted, spermatogenic cells were dropped in H group and D group. In addition, leydig cells were found to have swelling mitochondria in H group and D group, endoplasmic reticulum was reduced, and there was karyopyknosis accompany with sparse chromatin, all of which were ameliorated by B06. The protein expression of StAR was decreased in D group. The mRNA expression of StAR and P450scc was decreased in H group and D group, all of which were increased in B06 treatment group. There was no significant difference in the mRNA expression of P450c17, P450arom, 3β-HSD and 17β-HSD. CONCLUSION: B06 may increase serum testosterone and relieve the damage of testes from type 2 diabetic rats. B06 improves metabolic disorder by up-regulating mRNA expression of StAR and P450scc.     

Effect of lentinan on myocardial impairment in diabetic rats

AIM:To study the protective effect of lentinan against myocardial impairment in diabetic rats.METHODS:Morphology of myocardium from streptozocin induced diabetic rats treated with lentinan was observed under light microscopy(LM) and transmission electron microscopy(TEM). Activity of superoxide dismutase(SOD), nitric oxide synthase (NOS) and contents of malondialdehyde (MDA) and nitric oxide (NO) were detected biochemically in myocardial homogenate.RESULTS:Vacuolar degeneration, local lysis of myocardium and interstitial proliferation under LM and expansion of mitochondria, shortening of mitochondrial crest, lysis of myofibril and proliferation of interstitial collogenous fiber under TEM were observed. The activity of SOD decreased and the activity of NOS, the contents of NO, MDA increased, but the morphological change became slight in LNT-treatment group. Activity of SOD increased while activity of NOS and contents of MDA, NO decreased in LNT-treated rats compared with diabetic rats.CONCLUSION:LNT protectes diabetic myocardium, and the anti-lipid peroxidation and decreasing of NO level may be involved in it.     

Gene expression of 5α-reductase (type 2) in reproductive gland of pubertal diabetic rats

AIM: To study the molecular mechanism of reproduction dysfunction in pubertal diabetic rat, the level of 5α-reductase (type 2) mRNA in testis, epididymis and prostate in diabetic rat was detected. METHODS: The gene expression of 5α-reductase (type 2) was detected by Northern blot. RESULTS: In the caput of the epididymis, the expression of 5α-reductase (type 2) mRNA of D and ID groups was less than that of C group. CONCLUSION: The decreased expression of 5α-reductase (type 2) results in the decreased production of dihydrotestosterone, which influences the development and function of reproduction system in pubertal rats.     

Changes and clinical implications of plasma ANP,BNP and CNP levels in type 2 diabetic patients with vascular complications

AIM:To examine the changes and clinical implications of the plasma atrial natriuretic peptide (ANP), brain natriuretic peptide(BNP) and C-type natriuretic peptide(CNP) levels in type 2 diabetic patients with vascular complications. METHODS:9 subjects without diabetes, 34 diabetic patients without vascular complications and 23 diabetic patients with vascular complications were enrolled in the study and categorized into three groups. Plasma proANP, BNP fragment and N-terminal pro-CNP (NT-proCNP) were measured by enzyme linked immunosorbent assay (ELISA). The changes and associations of the plasma natriuretic peptide levels among three groups were analyzed. RESULTS:Compared with those in the controls and diabetics without vascular complications, the plasma proANP and BNP fragment levels in diabetic patients with vascular complications increased significantly (P<0.01). However, the plasma NT-proCNP level in this group decreased significantly (P<0.01). Nevertheless, no significant differences in the plasma proANP, BNP fragment and NT-proCNP levels among three subgroups (diabetics patients with macrovascular and/or microvascular complications) were observed (P>0.05). The plasma ANP level of diabetic patients with vascular complications was corelated significantly with the BNP levels (r=0.309, P<0.05). Furthermore, the ANP and BNP levels were correlated significantly with the CNP level (r=-0.374, P<0.05; r=-0.653, P<0.01). CONCLUSION:Measurement of the plasma ANP, BNP and CNP levels together may be a simple, cost-effective and reliable way to screen for diabetic patients with vascular complications.     

Measurement and analysis of microcirculation dysfunction in type 2 diabetic patients

AIM: To measure microcirculation function in type 2 diabetic patients and non-diabetic subjects with a new measurement method called capillary recruitment. METHODS: 276 type 2 diabetic patients in Shanghai downtown were enrolled and categorized into several groups, those with diabetes duration <5 years，5-10 years or ≥10 years, those with body mass index ≥25 kg/m2 or <25 kg/m2 and those with or without family history of diabetes. We determined skin capillary recruitment after arterial occlusion with capillaroscopy and compared the percentage increase of capillary density among these groups. 20 non-diabetic subjects were also measured.RESULTS: The average age of non-diabetic subjects was (60.56±6.73) years old. The average baseline capillary density was (36.25±8.78)/mm2, with an average peak capillary density of (48.97±10.24)/mm2. The average age of diabetic patients was (64.94±10.72) years old. The average baseline capillary density was (33.65±9.78)/mm2, with an average peak capillary density of (42.70±11.74)/mm2.The diabetes duration increased, as did the percent increase of capillary density ［(29.63%±13.85%)， (27.45%±12.23%)， (25.75%±10.90%), respectively］. The percentage increase of those with diabetes family history or body mass index ≥25 kg/m2 was significantly decreased in comparison with controls. There was no significant difference in the percent increase of capillary density between genders.CONCLUSION: We have evaluated the microcirculation function in type 2 diabetic patients and the results show a close relation between dysfunction of microcirculation and obesity, diabetes family history and diabetes duration.     

Effect of aerobic exercise on myenteric plexus and colonic dysfunction in type 2 diabetic rats

AIM: To observe the effect of aerobic exercise and dietary patterns on the colonic function of type 2 diabetic rats and the enteric nervous mechanism.METHODS: The rat model of type 2 diabetes was induced by high-fat diet (HFD) and streptozotocin (30 mg/kg, ip) injection, and the rats were divided into diabetes control (DC) group, HFD group, exercise (E) group and exercise combined with high fat diet (E+HFD) group. Some other healthy rats were arranged into normal control (NC) group. The rats in E group and E+HFD group received 8-week swimming training (5 d/week, 60 min/d). The colon samples were collected at the end of the 8th week for observation of the pathological changes by HE staining and for detection of colonic tension and expression of protein gene product 9.5(PGP9.5), substance P(SP) and vasoactive intestinal peptide (VIP).RESULTS: Diabetes induced significant myenteric plexus damages and marked reduction of neurons, while exercise protected the enteric nervous system from injuries. The expression of SP significantly increased in the rats with long-term aerobic exercise combined with a reasonable diet. However, high-fat diet combined with exercise did not obviously up-regulate SP. The positive expression of VIP in the colon significantly increased in both E group and E+HFD group. Aerobic exercise attenuated the atrophy and increased the tension in colonic smooth muscles.CONCLUSION: Diabetes induces muscular atrophy and tension attenuation in colonic smooth muscle, which can be reversed in some extent by aerobic exercise through the remolding of enteric nervous system.     

Alteration of p38 MAPK activity in lung tissue in diabetic rats

AIM: To observe the pathologic changes in lung and the role of p38 MAPKinase signal pathways in pulmonary alteration in diabetic rats. METHODS: Diabetic rats were induced by intraperitoneally injected streptozotozin (STZ). After 4 weeks, we observed the pathologic changes in lungs, tested protein kinase C (PKC) activities by isotope in lungs of model rats, tested transforming growth factor (TGF-β₁) by Western blotting and immunohistochemical analysis, and determined the expression of p38 MAPKinase mRNA using in situ hybridization.RESULTS: After STZ administration for 4 weeks, we observed thickened pulmonary capillary basal lamina and increased number of fibre in Diabetes mellitus (DM) rats. TGF-β₁ levels, PKC and p38 MAPK activities were also found increased. CONCLUSION: The increased activities of TGF-β₁ and p38 MAPK suggeste that TGF-β₁ may play an important role in diabetic lung, and hyperglycemia-PKC-p38 MAPK signal pathways may be involved in the pathogenesis of diabetes.     

Effect of insulin combined with selenium on myocardial remodeling in diabetic rats

AIM: To investigate the effects of insulin combined with selenium on myocardial remodeling in streptozotocin (STZ)-induced diabetic rats.METHODS: The animal model of diabetic cardiomyopathy was induced by intraperitoneal injection of STZ (50 mg/kg) in rats. The level of blood glucose was estimated using One Touch SureStep blood glucose meter. Hemoglobin A1c level was detected by microcolumn assay. Triglyceride and total cholesterol were measured by enzymatic method. Collagen content in the myocardium was determined by Mallory staining. The expression of tumor necrosis factor α (TNF-α) in the serum and myocardium was observed by the methods of ELISA and immunohistochemistry, respectively.RESULTS: Compared with control group, the animals in model group showed metabolic disorders of glucose and lipid, and the cardiac function declined significantly (P<0.01).The myocardial cells showed disorder of distribution, filament breakage and collagen hyperplasia,and serum and myocardial TNF-α levels were significantly elevated.Insulin in combination with selenium significantly decreased the levels of blood glucose and lipid, and markedly inhibited the expression of TNF-α in the serum and myocardium than those in the rats administered with insulin alone (P<0.01).CONCLUSION: Combination of insulin and selenium significantly improves the structure and function of the heart by down-regulation of TNF-α.