Narrow Results

This study investigates the effect of coronary artery disease (CAD) and Type2 Diabetes Mellitus (T2DM) on the measurement of nonlinear Pulse Rate Variability (PRV) parameters with respect to the control group. The effect of coronary artery disease with and without DM on nonlinear PRV parameters is aimed to compare with the control group including evaluation of any differences in PRV features between CAD groups with and without diabetes. Patients clinically diagnosed with CAD were recruited for this study. These were sub-grouped as (i) CAD with DM ($n=56$); (ii) CAD without DM ($n=9$); (iii) DM ($n=109$); (iv) Control group ($n=115$). The study was done by recording and analyzing 5 min of Pulse-Plethysmogram (PPG) recordings from left-hand index finger in sitting position. Nonlinear PRV analysis was performed using Poincaré plot analysis, Approximate Entropy (ApEn), Sample Entropy (SampEn), and Detrended Fluctuation Analysis (DFA) along with statistical analysis using student’s $t$-test at $p$-value $<$ 0.05. Major PRV features measuring heart rate complexity showed significantly lower values in diseased conditions (DM, CAD with and without DM) compared to the control group. No significant difference in any of the nonlinear parameters was found between CAD with and without DM groups. The result suggests that nonlinear PRV analysis using PPG signal recording could be very useful in the classification, measurement and prognosis of diseases due to cardiac-autonomic nervous system abnormalities like CAD and diabetes accurately using robust and reliable machine learning algorithms.

In this work we present a data-driven modeling of the insulin dynamics in different in silico patients using a recurrent neural network with output feedback. The inputs for the identification is the rate of insulin (μU / dl / min) applied to the patient, and blood glucose concentration. The output is insulin concentration (μU / ml) present in the blood stream. Once completed the off-line modeling, this model could be used for on-line monitoring of the insulin concentration for a better treatment. The learning law of the recurrent neural network is inspired by adaptive observer theory, and proven to be convergent in the parameters and stable in the Lyapunov sense, even with only 13 samples available. Simulation results are shown to validate the presented modeling.

Magnets were attached on auricular acupuncture points of diabetes patients. This treatment lowered the blood glucose levels and improved eye conditions.

In this study, we evaluated antihyperglycemic effects of American ginseng berry extract in diabetic ob/ob mice. Animals received daily intraperitoneal (IP) injections of the extract 150 mg/kg for 12 days. On days 5 and 12, the extract-treated ob/ob mice had significantly lower fasting blood glucose levels compared to day 0 (both p < 0.05). Glucose tolerance improved significantly, which was shown by overall glucose excursion, calculated as area under the curve (AUC) during the two-hour IP glucose tolerance test. The AUC decreased by 31.8% on day 12 compared to day 0 (p < 0.01). In addition, after 12 days of the berry extract treatment, a significant reduction in body weight (p < 0.01 compared to day 0) and a significant increase in body temperature (p < 0.01 compared to day 0) was noticeable. Our results support in vivo antihyperglycemic and antiobese activity of American ginseng berry extract that may prove to be of clinical importance in the prevention and treatment of Type 2 diabetes.

In this ex vivo study, the inhibitory activity of hypocrellin A (HA), a perylene quinonoid pigment isolated from the Chinese medicinal fungus Hypocrella bambuase, on protein kinase C (PKC) enzyme activity in insulin target tissues of obese Zucker rats was assessed. Pre-incubation with HA for 30 minutes significantly inhibited the activity of partially purified PKC enzyme from liver and soleus skeletal muscle in a dose-dependent manner (IC₅₀=0.07 and 0.26 μg/ml, respectively). HA produced a greater inhibitory effect in enzyme prepared from the liver than enzyme prepared from soleus muscle. Since total PKC activity in these two insulin target tissues is the net result of several different isoforms of PKC, and PKC-θ is a major isoform expressed in the soleus skeletal muscle, the present data suggest that the naturally occurring compound, HA, may selectively inhibit certain PKC isoforms other than PKC-θ. Further investigations are required to determine which PKC isoforms are most susceptible to HA and whether changes in PKC signaling during treatment with HA can reverse abnormalities of glucose and lipid metabolism in insulin resistant and diabetic states.

Prevention of diabetic gastrointestinal dysfunction is of utmost importance. The present study demonstrated that diacylglycerol kinase (DGK) activity in diabetic gastric smooth muscle in the resting state was approximately 3.5-fold greater than that in controls. However, oral administration of TJ-43 (1% of food intake) or subcutaneous insulin injection (12 units/kg/day) in streptozotocin-induced diabetic rats (DM) for 2 weeks prevented DGK abnormalities based on the control level. Increased DGK activity in the resting state of DM was inhibited significantly by R59022, neomycin or staurosporine; in contrast, these drugs did not affect DGK activity in controls, insulin-treated DM or TJ-43-treated DM. In controls, the endogenous phosphatidic acid (PA) level was inhibited significantly by R59022 or neomycin but not affected by staurosporine. On the other hand, these three drugs significantly inhibited endogenous PA levels in DM, and neomycin significantly inhibited endogenous PA levels in insulin-treated and TJ-43-treated DM. This suggests that TJ-43 could prevent alteration of DGK activity and PA formation without reduction of blood glucose levels. Moreover, these effects were greater than those of insulin treatment. Results suggested that TJ-43 treatment influenced the hyperreactivity of DGK and DAG formation via phospholipase C activity. In conclusion, TJ-43 can be recommended with respect to enhancement of the quality of life in patients displaying diabetic gastrointestinal complications.

The effects of Rosa rugosa on diabetic oxidative stress were investigated using rats with streptozotocin (STZ)-induced diabetes. The diabetic rats showed less body weight gain and heavier kidney and liver weights than normal rats, while the oral administration of Rosa rugosa at a dose of 100 or 200 mg/kg body weight/day for 20 days attenuated the physiological changes induced by diabetes. In addition, administrating Rosa rugosa to diabetic rats resulted in significant and dose-dependent decreases in the serum glucose and glycosylated protein levels, implying that Rosa rugosa improves the abnormal glucose metabolism that leads to oxidative stress. Diabetic rats had higher serum levels of superoxide and nitrite/nitrate. However, the administration of Rosa rugosa dose-dependently reduced the over-production of radicals associated with diabetes, suggesting Rosa rugosa is a radical scavenger that would play a crucial role in protecting against diabetic oxidative stress. Rosa rugosa significantly and dose-dependently reduced thiobarbituric acid-reactive substance levels in serum, hepatic and renal mitochondria, implying that Rosa rugosa would alleviate the oxidative stress associated with diabetes by inhibiting lipid peroxidation. This study provides evidence that Rosa rugosa has potential as a treatment for diabetes through attenuating oxidative stress induced by the diabetic condition

Nitric oxide (NO) is synthesized from L-arginine by nitric oxide synthase (NOS). Alternation of NOS expression is implicated in the pathogenesis of numerous secondary complications of diabetes. Aqueous extract of Ginseng radix has traditionally been used for the various disorders including diabetes. In this study, the effect of Ginseng radix on the NOS expression in the hippocampus of streptozotocin (STZ)-induced diabetic rats was investigated via nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Enhanced NOS expression was detected in the hippocampus of diabetic rats and administration of Ginseng radix suppressed NOS expression. Ginseng radix may aid the treatment of central nervous system complications in diabetes.

The aim of this study is to demonstrate the effects of Ananas comosus L. leaves on diabetic-dyslipidemic rats. Hypoglycemic and hypolipidemic activities of the ethanolic extract of Ananas comosus L. leaves (EEACL) were evaluated in normal and alloxan-induced diabetic rats by oral glucose tolerance test and an olive oil load test. Anti-diabetic, anti-hyperlipidemic and anti-oxidative activities of EEACL were also investigated in diabetic-dyslipidemic rats induced by alloxan and a high-fat/high-cholesterol diet. EEACL at the dose of 0.40 g/kg significantly inhibited the increase in blood glucose in diabetic rats in oral glucose tolerance test, but did not cause any hypoglycerimic activity in normal rats. It also significantly inhibited the increase in postprandial triglycerides (TG) levels in both normal and diabetic rats in olive oil load test. After 15 days of treatment of diabetic dyslipidemic rats, EEACL significantly decreased blood glucose (-51.0%, P<0.01), TG (-50.1%, P<0.01), TC (-23.3%, P<0.01), LDL-c (-47.9%, P<0.01) and glycated albumin (-25.4%, P<0.01) levels, significantly increased serum high-density lipoprotein cholesterol levels (66.2%, P<0.01) and prevented lower body weight of diabetes (11.8%, P<0.05), significantly lowered lipid peroxidation productions of blood (-27.8%, P<0.01), brain (-31.6%, P<0.05), liver (-44.5%, P<0.01) and kidneys (-72.2%, P<0.05) compared with those in untreated diabetic dyslipidemic rats. These data suggest that EEACL has anti-diabetic, anti-dyslipidemic and anti-oxidative activities, which may be developed into a new plant medicine for treatment of diabetes and its complications.

We observed that curry leaf (Murraya koenigii) extract possesses the property to decrease blood cholesterol and blood glucose levels in diabetic ob/ob mice. Mice received daily intraperitoneal injections of 80 mg/kg curry leaf extract for 10 consecutive days. The extract significantly decreased blood cholesterol level from 277.6 ± 16.6 mg/d (day 0) to 182.0 ± 15.3 mg/d (day 10, p < 0.01 compared with the change in vehicle group). The extract also significantly decreased blood glucose level from 387.0 ± 15.6 mg/dl (day 0) to 214.0 ± 26.6 mg/dl (day 10, p < 0.01). In addition, body weight was reduced after extract treatment. Our data suggest that curry leaf may be proved to be of clinical importance in improving the management of high cholesterol level and type 2 diabetes.

Euonymus alatus (E. alatus) has been used as a folk medicine for diabetes in China for more than one thousand years. In order to identify major active components, effects of different fractions of E. alatus on the plasma glucose levels were investigated in normal mice and alloxan-induced diabetic mice. Our results show that ethyl acetate fraction (EtOAc Fr.) displayed significant effects on reducing plasma glucose. In oral glucose tolerance, EtOAc Fr. at 17.2 mg/kg could significantly decrease the blood glucose of both normal mice and diabetic mice. After 4 weeks administration of the EtOAc Fr, when compared with the diabetic control, there were significant difference in biochemical parameters, such as glycosylated serum protein, superoxide dismutase and malondial dehyde, triglyceride, and total cholesterol, between alloxan-induced diabetic mice and the control group. Additional histopathological studies of pancreatic islets also showed EtOAc Fr. has beneficial effects on diabetic mice. Chemical analysis with three-dimensional HPLC demonstrated that the major components from EtOAc Fr were flavonoids and phenolic acids, which had anti-oxidative effects on scavenging DPPH-radical in vitro. All these experimental results suggest that EtOAc Fr. is an active fraction of E. alatus and can prevent the progress of diabetes. The mechanism of E. alatus for glucose control may be by stimulating insulin release, improving glucose uptake and improving oxidative-stress.

Oxidative stress is the root cause of diabetic macro- and microvascular complications. Biochemical and epidemiological studies indicate that current treatments for diabetes do not reduce risks of developing complications, suggesting their inability to alleviate the levels of oxidative stress. This study in streptozotocin (STZ)-induced diabetic rats was carried out to investigate the effect of combining the antidiabetic drug, metformin, with an ethanolic extract of Scutellaria baicalensis, a plant whose root is known for its radical scavenging activity. Three groups of STZ-induced diabetic rats were given the following treatments for 30 days: (1) metformin 500 mg/kg, (2) S. baicalensis 400 mg/kg, (3) metformin 500 mg/kg + S. baicalensis extract 400 mg/kg. In addition, vehicle-treated diabetic and nondiabetic controls were used in the experiment. The rats treated with S. baicalensis and metformin + S. baicalensis had elevated hepatic activities of the antioxidant enzymes — superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) compared to the vehicle- and metformin-treated diabetic groups (p < 0.05). Plasma and hepatic lipid peroxide concentrations in the herb-treated and herb + metformin-treated groups were also significantly reduced (p < 0.05). In addition, the combined treatment caused significant elevations of plasma and pancreatic insulin levels and reductions of plasma and hepatic triglycerides (TG) and cholesterol levels. The study thus showed that S. baicalensis enhanced the antidiabetic effect of metformin in STZ-induced diabetic rats by improving the antioxidant status. It also increased pancreatic insulin content as well as improved the lipid profile in these rats.

Hyperglycemia in diabetic conditions may cause oxidative stress in pancreatic ß-cells, leading to their dysfunction and insulin resistance within peripheral tissues. Previous studies suggest that American ginseng berry extract may have hypoglycemic effects, as well as offer antioxidant protection. We examined effects of American ginseng berry extract and ginsenoside Re in a pancreatic ß-cell line, MIN-6, to determine if these two properties are related. Cells were exposed to oxidative stress via hydrogen peroxide incubation and oxidative stress was measured by oxidation of 2′,7′-dichlorofluorescin diacetate. These cells showed a concentration-related response to hydrogen peroxide at 100–500 μM. In acute conditions where cells were treated with the extract for 10 min, we observed reduced oxidant injury suggesting direct scavenging effects. Chronic incubation of cells with the extract for 48 hours also demonstrated attenuation of oxidative stress. At high concentrations, Re showed a mild antioxidant effect in MIN-6 cells. Our insulin release observations also showed that the extract may help to increase insulin secretions from the cells. Our data suggest that the observed ability of ginseng to reduce blood glucose levels may be linked to its antioxidant effects on pancreatic ß-cells.

To investigate the effects of Korean ginseng (KG, Panax ginseng C.A. Meyer) and heat-processed Korean ginseng (H-KG) on diabetic renal damage, we used the streptozotocin-induced diabetic rat model in this study. The diabetes-induced physiological abnormalities at early-stage were attenuated by KG or H-KG administration through reducing the blood glucose level and improving renal function. The oxidative stress-induced increases in serum and renal thiobarbituric acid-reactive substance levels were significantly reduced by KG and H-KG administrations. Moreover, the protein expressions related to oxidative stress and advanced glycation endproducts were significantly reduced in diabetic rats and/or not significantly increased compared to normal rats by KG or H-KG administration. All of these beneficial effects of H-KG in diabetic rats were stronger than those of KG. Therefore, KG and H-KG may improve diabetic pathological conditions and prevent renal damage associated with diabetic nephropathy, and these protective effects of KG can be improved by heat-processing. This study provides scientific evidence that H-KG may be a potential therapeutic agent for pathological conditions associated with diabetic complications including diabetic nephropathy.

This study investigated the effects of Rehmannia glutinosa individually as well as in combination with the oral hypoglycemic agent, metformin in streptozotocin (STZ)-induced diabetic Wistar rats. R. glutinosa ethanolic extract was prepared and the constituents were characterized using fractionation by column chromatography, followed by high performance liquid chromatography-mass spectrometry. STZ (65 mg/kg) was injected intraperitoneally to induce diabetes in Wistar rats. The diabetic rats were divided into the following groups (each n = 6) and received the respective treatments for 30 days: (1) metformin (500 mg/kg), (2) R. glutinosa (200 mg/kg), (3) metformin (500 mg/kg) and R. glutinosa (200 mg/kg) and (4) diabetic control (DC). A reduction in plasma glucose levels caused by the herb was not as significant as metformin compared to the diabetic control (p < 0.05). However, R. glutinosa-treated group showed reductions in plasma C-reactive protein (CRP) levels compared to the diabetic controls (p < 0.05) as well as metformin-treated group (p < 0.05). An enhanced reduction in CRP concentration was observed in the group receiving both herb and metformin compared to metformin-treated group (p < 0.05). Reduction in CRP levels suggests an anti-inflammatory activity of the herb.

The anti-hyperglycemic and immunomodulatory activities of the ethanol extract from Paecilomyces Hepiali Chen (PHC), a Chinese medicine, were investigated in streptozotocin-induced type 1 diabetic (T1DM) mice. Male Balb/c mice, which were i.p. injected with streptozotocin (STZ, 50 mg/kg, for 5 consecutive days) on Day 7, were orally administered saline (the normal control and diabetic control group), Metformin (60 mg/kg, b.w., positive group), or the extract (100 mg/kg, b.w., PHC prevention group) from Day 1 to Day 28, Mice i.p. injected with streptozotocin (STZ, 50 mg/kg, b.w.) for 5 consecutive days prior to PHC treatment (100 mg/kg, b.w.) were used as the PHC treatment group. The effects of PHC on postprandial blood glucose concentrations, plasmatic insulin levels, morphology of pancreatic β cells and CD4⁺ T cells proliferation after 28-day treatment were monitored. Results showed that PHC administered 6 days before STZ induction of diabetes in mice significantly decreased blood glucose level (p < 0.01). An increase of insulin level was also observed as compared to those in the diabetic control group (p < 0.01). In addition, fewer inflammatory cells infiltrated the pancreatic islet and fewer β cells death by apoptosis within the inflamed islets were observed. More importantly, the CD4⁺ T cell proliferation was remarkably attenuated ex vivo in mice preventively treated with PHC (p < 0.01). In comparison to the PHC prevention group, no significant hypoglycemia, changes of insulin level and β cell protection were observed in mice treated with PHC after STZ administration. Our findings demonstrated that preventive administration of PHC protected β cells from apoptosis in type 1 diabetes induced by STZ, and the underlying mechanism may be involved in suppressing CD4⁺ T cells reaction, reducing inflammatory cells infiltration and protecting beta cell apoptosis in pancreatic islet.

Diabetes is a major medical problem that imperils public health. Over two thousand years ago, Traditional Chinese Medicine (TCM) called diabetes-related symptoms "Xiaoke" disease. In ancient China, TCM and Chinese herbal medicines were used widely in treating Xiaoke and abundant experience has been accumulated. This article discusses the TCM theory on diabetes and its achievements in the prevention and treatment of diabetes in the past. Using Chinese herbal medicine, recent progress in diabetes therapeutics, including data from clinical trials, are presented. Mechanistic studies from basic research are discussed. Yin-yang balance and a holistic approach of TCM may complement diabetes treatment in Western medicine. With continuous efforts, TCM could play a more important role in fighting this disease.

Diabetes mellitus is the leading cause of vascular complications such as atherosclerosis. This study was designed to investigate whether Prunella vulgaris (APV) would inhibit diabetic atherosclerosis in db/db mice with type 2 diabetes. The db/db mice were treated with high fat/high cholesterol (HFHC) diet and an aqueous extract of APV (100 and 200 mg/kg/day) for eight weeks to examine the long-term effect on metabolic abnormalities and diabetic atherosclerosis. APV treatment markedly lowered blood glucose and systolic blood pressure. The db/db mice experienced an increase in blood urea nitrogen as well as a decrease of creatinine clearance, the latter of which was restored by treatment with APV. Treatment with APV markedly decreased total plasma cholesterol, triglyceride, and LDL-cholesterol and also increased the HDL-cholesterol. In addition, malondialdehyde and TGF-β1 were decreased by treatment of APV. On the other hand, total NO level was decreased in db/db mice. However, the NO level was increased by treatment with APV, suggesting an association with vascular dysfunction. Vascular relaxation of aortic rings by acetylcholine or SNP-inducement was ameliorated by APV in a dose-dependent manner. Damage of vascular intima and hypertrophic of media were observed in db/db mice; however its dysfunction was improved by the treatment of APV. APV treatment significantly reduced the aortic expressions of ICAM-1, VCAM-1, ET-1, and nitrotyrosine. Furthermore, expression of eNOS in aortic was remarkably increased by APV treatment. Taken together, APV suppressed hyperglycemia and diabetic vascular dysfunction in HFHC diet-db/db mice. The present data suggest that Prunella vulgaris may prevent development of diabetic atherosclerosis.

The α-amylase and α-glucosidase inhibition activity of 92 Traditional Chinese Medicinal (TCM) herbs, which are permitted to be used as food ingredients, were evaluated using the high throughput assay developed in our laboratory. Among these herbs, twenty-seven of them possessed significant α-amylase inhibition activities ranging from 2.4 to 349.2 μmol AE/g (AE = acarbose equivalent) with inhibition concentrations at 50% inhibition (IC₅₀) from 16.0 to 2342.2 μg/mL, respectively. In addition, they showed α-glucosidase inhibition activities ranging from 0.5 to 31.6 μmolAE/g (IC₅₀ from 49.0 to 3385.5 μg/mL). The extracts of Rhizoma fagopyri dibotryis (Jīnqiáomài), Rosa rugosa (Méiguīhuā), Caulis polygoni multiflori (Shǒuwūténg), Fructus amomi (Shārén), Rhizoma alpiniae officinarum (Gāoliángjiāng), Folium ginkgo (Yínxìngyè) and Cortex cinnamomi (Ròuguì) showed the better inhibitory activities against both α-amylase and α-glucosidase. Our results illustrated that these food grade herbs are potent natural hypoglycemic agents and can be used as active ingredients for low glycemic index food production or TCM herbal formulations for controlling hyperglycemia.

Obese patients with type 2 diabetes mellitus (T2DM), which is characterized by hyperglycemia, are liable to more severe myocardial infarction. Semen Cassiae is proven to reduce serum lipid levels. This study investigated whether the Semen Cassiae extract (SCE) reduces myocardial ischemia and reperfusion (MI/R) injury with or without diabetes and the underlying mechanisms. The high-fat diet-fed streptozotocin (HFD-STZ) rat model was created as a T2DM model. Normal and DM rats received SCE treatment orally (10 mg/kg/day) for one week. Subsequently these animals were subjected to MI/R. Compared with the normal animals, DM rats showed increased plasma total cholesterol (TC) and triacylglycerol (TG), and more severe MI/R injury and cardiac functional impairment. SCE treatment significantly reduced the plasma TC and TG, improved the instantaneous first derivation of left ventricle pressure and reduced infarct size, decreased plasma creatine kinase and lactate dehydrogenase levels, and apoptosis index at the end of reperfusion in diabetic rats. Moreover, SCE treatment increased the antiapoptotic protein Akt and ERK1/2 phosphorylation levels. Pretreatment with a PI3K inhibitor wortmannin or an ERK1/2 inhibitor PD98059 not only blocked Akt and ERK1/2 phosphorylation respectively, but also inhibited the cardioprotective effects of SCE. However, SCE treatment did not show any effects on the MI/R injury in the normal rats. Our data suggest that SCE effectively improves myocardial function and reduces MI/R-induced injury in diabetic but not normal animals, which is possibly attributed to the reduced TC/TG levels and the triggered cell survival signaling Akt and ERK1/2.