Effects of habitual perilla (shiso) tea drinking on the incidence of diabetes mellitus in spontaneously diabetic Trii (SDT)rats

The anti-diabetic effect of perilla (shiso) tea was evaluated in vivo. When shiso tea was given to model rats that spontaneously developed diabetes mellitus (DM), the development of DM was decelerated. In oral glucose tolerance tests, the disappearance of blood glucose in rats administered shiso tea was reinforced. These results suggest that habitual drinking of shiso tea is effective in preventing the onset of diabetes.     

Effects of the aqueous extract of white tea (Camellia sinensis) in a streptozotocin-induced diabetes model of rats

White tea (WT) is very similar to green tea (GT) but it is exceptionally prepared only from the buds and young tea leaves of Camelia sinensis plant while GT is prepared from the matured tea leaves. The present study was investigated to examine the effects of a 0.5% aqueous extract of WT in a streptozotocin-induced diabetes model of rats. Six-week-old male Sprague-Dawley rats were divided into 3 groups of 6 animals in each group namely: normal control (NC), diabetic control (DBC) and diabetic white tea (DWT). Diabetes was induced by an intraperitoneal injection of streptozotocin (65 mg/kg BW) in DBC and DWT groups except the NC group. After 4 weeks feeding of 0.5% aqueous extracts of WT, the drink intake was significantly (P < 0.05) increased in the DWT group compared to the DBC and NC groups. Blood glucose concentrations were significantly decreased and glucose tolerance ability was significantly improved in the DWT group compared to the DBC group. Liver weight and liver glycogen were significantly increased and serum total cholesterol and LDL-cholesterol were significantly decreased in the DWT group compared to the DBC group. The food intake, body weight gain, serum insulin and fructosamine concentrations were not influenced by the consumption of WT. Data of this study suggest that the 0.5% aqueous extract of WT is effective to reduce most of the diabetes associated abnormalities in a steptozotocin-induced diabetes model of rats.     

Major Water-Soluble Polyphenols,Proanthocyanidins, in Leaves of Persimmon (Diospyros kaki) and Their α-Amylase Inhibitory Activity

The amounts and compositions of polyphenol in persimmon leaves and persimmon leaf tea were investigated. The predominant polyphenols in fresh leaves were water-soluble, and the contents reached a maximum (2.40% w/w) in June, and then gradually decreased. Separation of them followed by thiolytic degradation revealed that the major components were unique proanthocyanidin oligomers consisting of four heterogeneous extension units, including epigallocatechin-3-O-gallate. Persimmon leaf tea also contained similar proanthocyanidins with similar compositional units. Oral administration of starch with polyphenol concentrate of persimmon leaf tea resulted in a significant and dose-dependent decrease in the blood glucose level in Wistar rats. This effect is considered to be due to inhibition of pancreas α-amylase. These results indicate that persimmon leaf tea containing peculiar proanthocyanidins has a significant role in suppressing blood glucose elevation after starch intake, and that the best harvest time is June.     

Hypotriacylglycerolemic and Antiobesity Properties of a New Fermented Tea Product Obtained by Tea-Rolling Processing of Third-Crop Green Tea (Camellia sinensis) Leaves and Loquat (Eriobotrya japonica) Leaves

We manufactured a new fermented tea by tea-rolling processing of third-crop green tea (Camellia sinensis) leaves and loquat (Eriobotrya japonica) leaves. The mixed fermented tea extract inhibited pancreatic lipase activity in vitro, and effectively suppressed postprandial hypertriacylglycerolemia in rats. Rats fed a diet containing 1% freeze-dried fermented tea extract for 4 weeks had a significantly lower liver triacylglycerol concentration and white adipose tissue weight than those fed the control diet lacking fermented tea extract. The activity of fatty acid synthase in hepatic cytosol markedly decreased in the fermented tea extract group as compared to the control group. The serum and liver triacylglycerol- and body fat-lowering effects of the mixed fermented tea extract were strong relative to the level of dietary supplementation. These results suggest that the new fermented tea product exhibited hypotriacylglycerolemic and antiobesity properties through suppression of both liver fatty acid synthesis and postprandial hypertriacylglycerolemia by inhibition of pancreatic lipase.     

Reduction of post-prandial hyperglycemia by mulberry tea in type-2 diabetes patients

Aim

The dietary contents have a very important role in the management of metabolic syndrome along with type 2 diabetes mellitus (T2DM). Indian diet contains a large amount of carbohydrates that set off unpredictable blood sugar fluctuations and leads to increased risk of diabetic complications. The aim of the present study was to identify the effect of mulberry tea in the reduction of abnormally high postprandial blood glucose (PPG) levels in T2DM patients.

Methods

The study design was follow-up T2DM, 20 diabetic patients were given plain tea (control) and 28 diabetic patients were given mulberry tea (test subject) to measure the effect of mulberry tea on fasting blood glucose and PPG levels. Fasting blood glucose samples were collected after a standard breakfast. The PPG levels were recorded after the consumption of 70 ml tea along with 1 teaspoon of sugar after 90 min in all 48 patients.

Results

Fasting blood glucose levels in control and test group samples were found to be 178.55 ± 35.61 and 153.50 ± 48.10, respectively. After the consumption of plain tea and mulberry tea, the PPG values were recorded as 287.20 ± 56.37 and 210.21 ± 58.73, respectively. A highly significant (p < 0.001) change in the PPG level was observed in response to mulberry tea in all the test patients compared with control. Moreover, the effect size was also found to be very large (1.31).

Conclusion

Mulberry tea suppresses postprandial rise of blood glucose levels after 90 min of its consumption.     

Effect of exposure to 50 Hz magnetic field with or without insulin on blood–brain barrier permeability in streptozotocin‐induced diabetic rats

We investigated the effect of long‐term exposure to modulation magnetic field (MF), insulin, and their combination on blood–brain barrier (BBB) permeability in a diabetic rat model. Fifty‐three rats were randomly assigned to one of six groups: sham, exposed to no MF; MF, exposed to MF; diabetes mellitus (DM), DM induced with streptozotocin (STZ); DM plus MF (DMMF); DM plus insulin therapy (DMI); and DM plus insulin therapy plus MF (DMIMF). All the rats underwent Evans blue (EB) measurement to evaluate the BBB 30 days after the beginning of experiments. The rats in MF, DMMF, and DMIMF groups were exposed to MF (B = 5 mT) for 165 min every day for 30 days. Mean arterial blood pressure (MABP), body mass, and serum glucose level of the study rats were recorded. The extravasation of brain EB of the MF, DM, DMMF, DMI, and DMIMF groups was higher than that of the sham group and the extravasation of right hemisphere of the DMIMF group was highest (P < 0.05). The post‐procedure body mass of the sham and MF groups were significantly higher than those of the DM and DMMF groups (P < 0.05). In the DM, DMMF, DMI, and DMIMF groups, the baseline glucose was significantly lower than the post‐procedure glucose (P < 0.05). DM and MF increase BBB permeability; in combination, they cause more increase in BBB permeability, and insulin decreases their effect on BBB. Improved glucose metabolism may prevent body mass loss and the hypoglycemic effect of MF. DM increases MABP but MF causes no additional effect. Bioelectromagnetics 31:262–269, 2010. © 2009 Wiley‐Liss, Inc.     

Development and characterization of a novel rat model of type 2 diabetes mellitus: the UC Davis type 2 diabetes mellitus UCD-T2DM rat

The prevalence of type 2 diabetes (T2DM) is increasing, creating a need for T2DM animal models for the study of disease pathogenesis, prevention, and treatment. The purpose of this project was to develop a rat model of T2DM that more closely models the pathophysiology of T2DM in humans. The model was created by crossing obese Sprague-Dawley rats with insulin resistance resulting from polygenic adult-onset obesity with Zucker diabetic fatty-lean rats that have a defect in pancreatic beta-cell function but normal leptin signaling. We have characterized the model with respect to diabetes incidence; age of onset; longitudinal measurements of glucose, insulin, and lipids; and glucose tolerance. Longitudinal fasting glucose and insulin data demonstrated progressive hyperglycemia (with fasting and fed glucose concentrations >250 and >450 mg/dl, respectively) after onset along with hyperinsulinemia resulting from insulin resistance at onset followed by a progressive decline in circulating insulin concentrations, indicative of beta-cell decompensation. The incidence of diabetes in male and female rats was 92 and 43%, respectively, with an average age of onset of 6 mo in males and 9.5 mo in females. Results from intravenous glucose tolerance tests, pancreas immunohistochemistry, and islet insulin content further support a role for beta-cell dysfunction in the pathophysiology of T2DM in this model. Diabetic animals also exhibit glycosuria, polyuria, and hyperphagia. Thus diabetes in the UC Davis-T2DM rat is more similar to clinical T2DM in humans than in other existing rat models and provides a useful model for future studies of the pathophysiology, treatment, and prevention of T2DM.     

Retinol‐binding Protein 4 (RBP4) Protein Expression Is Increased in Omental Adipose Tissue of Severely Obese Patients

Visceral fat has been linked to insulin resistance and type 2 diabetes mellitus (T2DM); and emerging data links RBP4 gene expression in adipose tissue with insulin resistance. In this study, we examined RBP4 protein expression in omental adipose tissue obtained from 24 severely obese patients undergoing bariatric surgery, and 10 lean controls (4 males/6 females, BMI = 23.2 ± 1.5 kg/m²) undergoing elective abdominal surgeries. Twelve of the obese patients had T2DM (2 males/10 females, BMI: 44.7 ± 1.5 kg/m²) and 12 had normal glucose tolerance (NGT: 4 males/8 females, BMI: 47.6 ± 1.9 kg/m²). Adipose RBP4, glucose transport protein‐4 (GLUT4), and p85 protein expression were determined by western blot. Blood samples from the bariatric patients were analyzed for serum RBP4, total cholesterol, triglycerides, and glucose. Adipose RBP4 protein expression (NGT: 11.0 ± 0.6; T2DM: 11.8 ± 0.7; lean: 8.7 ± 0.8 arbitrary units) was significantly increased in both NGT (P = 0.03) and T2DM (P = 0.005), compared to lean controls. GLUT4 protein was decreased in both NGT (P = 0.02) and T2DM (P = 0.03), and p85 expression was increased in T2DM subjects, compared to NGT (P = 0.03) and lean controls (P = 0.003). Regression analysis showed a strong correlation between adipose RBP4 protein and BMI for all subjects, as well as between adipose RBP4 and fasting glucose levels in T2DM subjects (r = 0.76, P = 0.004). Further, in T2DM, serum RBP4 was correlated with p85 expression (r = 0.68, P = 0.01), and adipose RBP4 protein trended toward an association with p85 protein (r = 0.55, P = 0.06). These data suggest that RBP4 may regulate adiposity, and p85 expression in obese‐T2DM, thus providing a link to impaired insulin signaling and diabetes in severely obese patients.     

Deterioration of Bone Quality by Streptozotocin (STZ)-Induced Type 2 Diabetes Mellitus in Rats

Patients with diabetes mellitus (DM) have various skeletal disorders and bone quality can be impaired in DM leading to fractures. Wistar albino male rats (270?C300?g; n?=?16) were assigned randomly to nondiabetic and diabetic rats (single dose intravenous injection of 45?mg/kg streptozotocin). All rats in each group were perpetuated for 8?weeks, and blood glucose levels as well as body weights were measured once weekly. Biomechanical measurements were performed at the mid-diaphysis of the left femur with tensile test. Extrinsic and intrinsic properties were measured or calculated. Bone mineral density (BMD) was also evaluated and measured by dual-energy X-ray absorptiometry. Cross-sectional area of the femoral shaft was evaluated by computerized tomography. Blood glucose levels in diabetic rats were significantly increased compared to that of the nondiabetic rats, while the body and femur weights were decreased (P?<?0.05). In respect to the BMD, cross-sectional area and femur length, there were no statistically significant differences between the nondiabetic and diabetic rats (P?>?0.05). The maximum load, ultimate stress, and toughness endpoints in diabetic rats were significantly decreased compared to that of the nondiabetics (P?<?0.05). There were no statistically significant differences between the nondiabetic and diabetic rats with regard to the displacement and stiffness (P?>?0.05). Femurs of diabetic rats had less absorbed energy than that in nondiabetics (P?<?0.05). Ultimate strain was lower in diabetic rats than that in nondiabetics, while the elastic modulus was higher (P?>?0.05). The bone quality of rats is decreased by streptozotocin-induced type 2 diabetes mellitus.     

Therapeutic effect of green tea extract on oxidative stress in aorta and heart of streptozotocin diabetic rats

Hyperglycemia induced oxidative stress has been proposed as a cause of many complications of diabetes including cardiac dysfunction. The present study depicts the therapeutic effect of green tea extract on oxidative stress in aorta as well as heart of streptozotocin diabetic rats. Six weeks after diabetes induction, green tea was administered orally for 4 weeks [300 mg (kg body weight)(-1) day (-1)]. In aorta and heart of diabetic rats there was a significant increase in the activity of superoxide dismutase, catalase and glutathione peroxidase with an increase in lipid peroxides. Diabetic rats showed a significant decrease in the levels of serum and cardiac glutathione. Green tea administration to diabetic rats reduced lipid peroxides and activity of antioxidant enzymes whereas increased glutathione content. The results demonstrate that the induction of antioxidant enzymes in diabetic rats is not efficient and sufficient to reduce the oxidative stress. But green tea by providing a competent antioxidative mechanism ameliorates the oxidative stress in the aorta and heart of diabetic rats. The study suggests that green tea may provide a useful therapeutic option in the reversal of oxidative stress induced cardiac dysfunction in diabetes mellitus.     

Antioxidant and Neuroprotective Properties of Sour Tea (Hibiscus sabdariffa, calyx) and Green Tea (Camellia sinensis) on some Pro-oxidant-induced Lipid Peroxidation in Brain in vitro

Oxidative stress is the cause of neurodegenerative disorders such as Lou Gehrig’s disease, Parkinson’s disease, and Huntington’s disease; one practical way to prevent and manage neurodegenerative diseases is through the eating of food rich in antioxidants (dietary means). This present study sought to compare the ability of aqueous extract of sour tea (Hibiscus sabdariffa, calyx) and green tea (Camellia sinensis) to prevent some pro-oxidant [Fe (II), sodium nitroprusside, quinolinic acid]-induced lipid peroxidation in rat’s brain in vitro. Aqueous extracts of both teas were prepared (1 g tea in 100 ml of hot water). Thereafter, the ability of the extracts to prevent 25 μM FeSO₄, 7 μM sodium nitroprusside, and 1 mM quinolinic acid-induced lipid peroxidation in isolated rat’s brain tissue preparation was determined in vitro. Subsequently, the total phenol content, reducing power, Fe (II) chelating and OH radical scavenging ability were determined. The results of the study revealed that both teas significantly (P < 0.05) inhibit lipid peroxidation in basal and pro-oxidant-induced lipid peroxidation in the rat’s brain homogenates in a dose-dependent manner. Also, the teas had high total phenol content [sour (13.3 mg/g); green (24.5 mg/g)], reducing power, and Fe (II) chelating and OH radical scavenging ability (except sour tea). However, green tea had a significantly higher (P < 0.05) ability to inhibit lipid peroxidation in both the basal and pro-oxidant-induced lipid peroxidation in rat’s brain homogenates in vitro. Therefore, it is obvious from the study that both teas had high antioxidant properties and could inhibit Fe²⁺, sodium nitroprusside, and quinolinic acid-induced lipid peroxidation in brain. However, green tea had a higher inhibitory effect, which may probably be due to its high total phenol content, reducing power, Fe (II) chelating ability, and OH radical scavenging ability.     

Chronic alcohol consumption,type 2 diabetes mellitus,insulin-like growth factor-I (IGF-I), and growth hormone (GH) in ethanol-treated diabetic rats

Aims

Alcohol has deleterious influences on glucose metabolism which may contribute to the development of type 2 diabetes mellitus (T2DM). Insulin-like growth factor I (IGF-I) and growth hormone (GH), which interact with insulin to modulate metabolic control, have been shown to be related to impaired glucose tolerance. This study was conducted to assess the possibility that altered circulating IGF-I and GH levels contribute to the exacerbation of T2DM by alcohol use in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats.

Main method

OLETF rats were pair-fed a Lieber-DeCarli Regular Ethanol diet and LETO rats were pair-fed a control diet for 6 weeks. At 6 weeks, an Intraperitoneal Glucose Tolerance Test (IP-GTT) was performed and IGF-I and GH levels were evaluated.

Key findings

Prior to an IP-GTT, OLETF-Ethanol (O-E) group had significantly a decrease in the mean glucose levels compared to OLETF-Control (O-C) group. At 120 min post IP-GTT, the O-E group had significantly an increase in the mean glucose levels compared to O-C group. The serum IGF-I levels were significantly lower and the serum GH levels were significantly higher in the O-E group than in L-C group.

Significance

These results suggest that IGF-I and GH are prominent in defining the risk and development of T2DM, and may be adversely affected by heavy alcohol use, possibly mediating its diabetogenic effects. Thus, the overall glucose intolerance in the setting of alcoholism may be attributable to inappropriate alteration of IGF-I and GH levels.     

Enhanced autophagy plays a cardinal role in mitochondrial dysfunction in type 2 diabetic Goto-Kakizaki (GK) rats: ameliorating effects of (-)-epigallocatechin-3-gallate

Oxidative stress and mitochondrial dysfunction are known to play important roles in type 2 diabetes mellitus (T2DM) and insulin resistance. However, the pathology of T2DM remains complicated; in particular, the mechanisms of mitochondrial dysfunction in skeletal muscle and other insulin-sensitive tissues are as yet unclear. In the present study, we investigated the underlying mechanisms of oxidative stress and mitochondrial dysfunction by focusing on mitochondrial dynamics, including mitochondrial biogenesis and autophagy, in skeletal muscle of a nonobese diabetic animal model--the Goto-Kakizaki (GK) rat. The results showed that GK rats exhibited impaired glucose metabolism, increased oxidative stress and decreased mitochondrial function. These dysfunctions were found to be associated with induction of LC3B, Beclin1 and DRP1 (key molecules mediating the autophagy pathway), while they appeared not to affect the mitochondrial biogenesis pathway. In addition, (-)-epigallocatechin-3-gallate (EGCG) was tested as a potential autophagy-targeting nutrient, and we found that EGCG treatment improved glucose tolerance and glucose homeostasis in GK rats, and reduced oxidative stress and mitochondrial dysfunction in skeletal muscle. Amelioration of excessive muscle autophagy in GK rats through the down-regulation of the ROS-ERK/JNK-p53 pathway leads to improvement of glucose metabolism, reduction of oxidative stress and inhibition of mitochondrial loss and dysfunction. These results suggest (a) that hyperglycemia-associated oxidative stress may induce autophagy through up-regulation of the ROS-ERK/JNK-p53 pathway, which may contribute to mitochondrial loss in soleus muscle of diabetic GK rats, and (b) that EGCG may be a potential autophagy regulator useful in treatment of insulin resistance.     

Effect of green tea and black tea on the metabolisms of mineral elements in old rats

A 2-mo experiment with the white Sprague-Dawley (SD) rats was conducted to investigate the effect of the water extracts of black tea (BTWE) and green tea (GTWE) and the black tea leaves (BTF) and the green tea leaves (GTF) on the metabolism of mineral elements. One hundred eight 12-mo-old white SD rats were randomly divided into 13 groups; 6 of these drank the BTWE or GTWE in which the water extracts concentrations of black tea or green tea were, respectively, 0.6%, 1.2%, and 2.4%, and 6 of these had black tea leaves (BTF) and green tea leaves (GTF) added in which the contents of BTF or GTF were, respectively, 0.5%, 1.0%, and 2.0%, one of these was control. The teas and their water extracts could promote the absorption of manganese and copper. In GTF, BTF, GTWE, and BTWE, the apparent absorption rates of manganese were significantly increased. The manganese contents in the tibia were also elevated, and the differences between GTWE and GTF were significant. The apparent absorption rates of copper and the copper contents in the tibia were increased, but not significantly. The teas and their water extracts inhibited the absorption of calcium (p > 0.05) and iron (p < 0.05). The cerebrum calcium contents were significantly decreased, but the contents of calcium and iron in tibia were not significantly changed. Compared with the control, although the apparent absorption rates of aluminum in all experimental groups were not observed to be different, the aluminum contents in the tibia (p > 0.05) and cerebrum (p < 0.05) were increased. GTF and GTWE decreased the apparent absorption rates of zinc, but BTF and BTWE increased them; the zinc contents in tibia were a little improved, whereas its contents in the cerebrum were gradually decreased with the increase of tea leaves dose and tea concentration.     

Effect of (-)-epigallocatechin-3-gallate on glucose-induced human serum albumin glycation

Abstract

(-)-Epigallocatechin-3-gallate (EGCg) is a naturally occurring polyphenol found in plant-based foods and beverages such as green tea. Although EGCg can eliminate carbonyl species produced by glucose autoxidation and thus can inhibit protein glycation, it is also reported to be a pro-oxidant that stimulates protein glycation in vitro. To better understand the balance between antioxidant and pro-oxidant features of EGCg, we evaluated EGCg-mediated bioactivities in a human serum albumin (HSA)/glucose model by varying three different parameters (glucose level, EGCg concentration, and time of exposure to EGCg). Measurements of glycation-induced fluorescence, protein carbonyls, and electrophoretic mobility showed that the level of HSA glycation was positively related to the glucose level over the range 10–100 mM during a 21-day incubation at 37°C and pH: 7.4. Under mild glycemic pressure (10 mM), long exposure to EGCg enhanced HSA glycation, while brief exposure to low concentrations of EGCg did not. Under high glycemic pressure (100 mM glucose), long exposure to EGCg inhibited glycation. For the first time we showed that brief exposure to EGCg reversed glycation-induced fluorescence, indicating a restorative effect. In conclusion, our research identified glucose level, EGCg concentration, and time of exposure as critical factors dictating EGCg bioactivities in HSA glycation. EGCg did not affect HSA glycation under normal physiological conditions but had a potential therapeutic effect on HSA severely damaged by glycation.     

有氧运动与饮食控制对2型糖尿病大鼠肝chemerin及其受体CMKLR1的影响

目的：研究4周有氧运动与饮食控制对2型糖尿病（DM）大鼠肝chemerin及其受体趋化因子样受体1（CMKLR1）的影响及其在改善糖脂代谢中的影响。方法：50只雄性SD大鼠随机分为正常对照组（Con,n=6）和糖尿病造模组（n=44）。采用高脂高糖饲料联合小剂量链脲佐菌素（STZ）（30 mg/kg）的方法制备2型糖尿病模型大鼠。造模成功的DM大鼠随机分为4组（n=6）：糖尿病对照组（DM）、糖尿病运动组（EDM）、改喂普通饲料的糖尿病饮食控制组（NDM）和糖尿病运动+饮食控制组（ENDM）。运动组大鼠进行为期4周中等强度跑台有氧运动,每周运动6 d。采用罗氏血糖仪检测大鼠空腹血糖（FBG）,全自动生化分析仪检测大鼠血清总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白（LDL）水平,real time PCR和Western blot分别检测大鼠肝chemerin、CMKLR1的mRNA和蛋白水平。结果：DM大鼠FBG和血清TC、TG、LDL水平显著升高的同时,肝chemerin和CMKLR1的mRNA和蛋白水平显著增加;4周有氧运动和/或饮食控制显著降低EDM、NDM和ENDM组FBG和血清TC、TG、LDL的同时,显著降低这3组大鼠的肝chemerin蛋白水平,其中ENDM组降低最显著（P<0.01）;NDM和ENDM组大鼠的肝CMKLR1蛋白水平升高（P<0.01）。结论：4周有氧运动和/或饮食控制降低2型糖尿病大鼠的肝chemerin蛋白水平、增加CMKLR1蛋白水平,这可能与其改善糖尿病大鼠的糖脂代谢有关。     

Synthesis and hypoglycemic activity of <Emphasis Type="Italic">Bis</Emphasis>(L-malato)oxovanadium(IV)

In order to create new oral vanadyl organic complexes-based drugs for the treatment of diabetes mellitus we have originally synthesized a biligand vanadyl derivative of L-malic acid (bis(L-malato)oxovanadium(IV)) and investigated its potential as a novel hypoglycemic agent using the experimental streptozotocin-induced diabetes in rats. The oral administration of bis(L-malato)oxovanadium(IV) with drinking water significantly reduced blood and urinary glucose concentrations and also the level of glycated proteins in the streptozotocin-diabetic rats.     

Influence of glyco-oxidation on complexes between fibrin(ogen) and insulin-like growth factor-binding protein-1 in patients with diabetes mellitus type 2

Fibrinogen and insulin-like growth factor-binding protein-1 (IGFBP-1) are tightly connected to metabolic changes and complications in patients with diabetes mellitus (DM), and since they mutually interact to form complexes in plasma, we investigated whether and to what extent IGFBP-1/fibrinogen complexes change due to glyco-oxidative processes in DM and whether they participate in fibrin clot formation. These complexes were determined by immunoblotting in plasma samples from healthy adults and patients with DM type 2 (DM2). The influence of glyco-oxidation in vitro on the complexes was also investigated. Amounts of IGFBP-1/fibrinogen complexes in plasma from patients with DM2 were slightly but not significantly lower than in healthy persons. Such complexes in patients’ samples participated in fibrin clot formation to a significantly decreased extent. In vitro experiments with glucose or methylglyoxal (MGO) as reactive agents demonstrated that the complexes underwent glyco-oxidative modification leading to reduced formation and/or stability. Extensively oxidized fibrinogen almost completely lost its ability to bind IGFBP-1. The reduced affinity of fibrinogen for IGFBP-1 accompanying diabetes may potentially shift the equilibrium to liberate more IGFBP-1 (and possibly insulin-like growth factor (IGF)-I) able to activate platelets during coagulation, so contributing to the hypercoagulation state together with other factors. This hypothesis, however, needs further examination.     

Glucose sensing by gut endocrine cells and activation of the vagal afferent pathway is impaired in a rodent model of type 2 diabetes mellitus

Glucose in the gut lumen activates gut endocrine cells to release 5-HT, glucagon-like peptide 1/2 (GLP-1/2), and glucose-dependent insulinotropic polypeptide (GIP), which act to change gastrointestinal function and regulate postprandial plasma glucose. There is evidence that both release and action of incretin hormones is reduced in type 2 diabetes (T2D). We measured cellular activation of enteroendocrine and enterochromaffin cells, enteric neurons, and vagal afferent neurons in response to intestinal glucose in a model of type 2 diabetes mellitus, the UCD-T2DM rat. Prediabetic (PD), recent-diabetic (RD, 2 wk postonset), and 3-mo diabetic (3MD) fasted UCD-T2DM rats were given an orogastric gavage of vehicle (water, 0.5 ml /100 g body wt) or glucose (330 μmol/100 g body wt); after 6 min tissue was removed and cellular activation was determined by immunohistochemistry for phosphorylated calcium calmodulin-dependent kinase II (pCaMKII). In PD rats, pCaMKII immunoreactivity was increased in duodenal 5-HT (P < 0.001), K (P < 0.01) and L (P < 0.01) cells in response to glucose; glucose-induced activation of all three cell types was significantly reduced in RD and 3MD compared with PD rats. Immunoreactivity for GLP-1, but not GIP, was significantly reduced in RD and 3MD compared with PD rats (P < 0.01). Administration of glucose significantly increased pCaMKII in enteric and vagal afferent neurons in PD rats; glucose-induced pCaMKII immunoreactivity was attenuated in enteric and vagal afferent neurons (P < 0.01, P < 0.001, respectively) in RD and 3MD. These data suggest that glucose sensing in enteroendocrine and enterochromaffin cells and activation of neural pathways is markedly impaired in UCD-T2DM rats.     

定量蛋白质组学研究揭示知母可缓解2型糖尿病模型大鼠肝脏代谢异常

2型糖尿病(type 2 diabetes mellitus, T2DM)是一种在全球范围内广泛存在的代谢性疾病,不及时治疗可能会引发众多危及生命的并发症。肝脏代谢在糖尿病发生发展的过程中扮演着至关重要的角色。目前已有报道中药知母用于缓解胰岛素抵抗及糖尿病,但其能否缓解糖尿病中肝脏代谢的异常仍有待深入研究。因此,提取了高脂饮食和化学药物链脲佐菌素(streptozotocin, STZ)诱导的2型糖尿病大鼠模型、知母提取物处理的2型糖尿病大鼠模型、高脂饮食大鼠模型以及正常饮食大鼠对照组的肝脏蛋白,通过基于质谱的定量蛋白质组学串联质量标签(tandem mass tag, TMT)标记技术获得定量蛋白质组数据。利用生物信息学软件对各组数据进行层次聚类分析及主成分分析,并以P<0.05,差异倍数(fold change)>1.5作为阈值标准进行火山图分析,发现知母提取物治疗组相较未治疗组与正常对照组更接近,表明肝脏组织定量蛋白质组数据能够反映知母提取物对2型糖尿病大鼠模型的治疗效果。筛选获得了表达水平与知母提取物治疗密切相关的关键蛋白簇。利用在线网站分析蛋白簇的GO功能与KEG...