http://www.hindawi.comThe latest articles from Hindawi Publishing Corporation© 2012, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/edr/2012/859186/The purpose of this study was to determine whether levels of interleukin-6 (IL-6) in childhood are related to insulin resistance in adolescence. Further, to explore how fatness and cardiorespiratory fitness (VO2peak) moderate this relationship. Methods. 292 nine-year-old children (n=292) were followed for 4 years. Anthropometrics and VO2peak were measured. Fasting blood samples were analyzed for IL-6, insulin, and glucose. Homeostasis model assessment (HOMA-IR) was used as a measure of insulin resistance. Results. For girls but not boys, levels of IL-6 at age 9 yrs correlated with HOMA-IR at age 13 yrs: r=0.223, P=0.008. Girls with IL-6 levels within the highest quartile at age 9 yrs had an odds ratio of 3.68 (CI = 1.58–8.57) being in the highest quartile of HOMA-IR four years later. Conclusion. In this cohort, IL-6 levels in childhood were related to insulin resistance in adolescence, but only for girls.Anna Bugge, Bianca El-Naaman, Robert G. McMurray, Karsten Froberg, Claus Henrik Nielsen, Klaus Müller, and Lars Bo AndersenCopyright © 2012 Anna Bugge et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/416254/Insulin resistance and loss of β-cell mass cause Type 2 diabetes (T2D). The objective of this study was to generate a nongenetic mouse model of T2D. Ninety-six 6-month-old C57BL/6N males were assigned to 1 of 12 groups including (1) low-fat diet (LFD; low-fat control; LFC), (2) LFD with 1 i.p. 40 mg/kg BW streptozotocin (STZ) injection, (3), (4), (5), (6) LFD with 2, 3, 4, or 5 STZ injections on consecutive days, respectively, (7) high-fat diet (HFD), (8) HFD with 1 STZ injection, (9), (10), (11), (12) HFD with 2, 3, 4, or 5 STZ injections on consecutive days, respectively. After 4 weeks, serum insulin levels were reduced in HFD mice administered at least 2 STZ injections as compared with HFC. Glucose tolerance was impaired in mice that consumed HFD and received 2, 3, or 4 injections of STZ. Insulin sensitivity in HFD mice was lower than that of LFD mice, regardless of STZ treatment. Islet mass was not affected by diet but was reduced by 50% in mice that received 3 STZ injections. The combination of HFD and three 40 mg/kg STZ injections induced a model with metabolic characteristics of T2D, including peripheral insulin resistance and reduced β-cell mass.Elizabeth R. Gilbert, Zhuo Fu, and Dongmin LiuCopyright © 2011 Elizabeth R. Gilbert et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/625813/TNF-related apoptosis-inducing ligand (TRAIL) is an important component of the immune system. Although it is well acknowledged that it also has an important role in Type 1 Diabetes (T1D) development, this presumed role has not yet been clearly revealed. Streptozotocin (STZ) and Cyclophosphamide (CY) are frequently used agents for establishment or acceleration of T1D disease in experimental models, including the non-obese diabetic (NOD) mice. Although such disease models are very suitable for diabetes research, different expression patterns for various T1D-related molecules may be expected, depending on the action mechanism of the applied agent. We accelerated diabetes in female NOD mice using STZ or CY and analyzed the expression profiles of TRAIL ligand and receptors throughout disease development. TRAIL ligand expression followed a completely different pattern in STZ- versus CY-accelerated disease, displaying a prominent increase in the former, while appearing at reduced levels in the latter. Decoy receptor 1 (DcR1) expression also increased significantly in the pancreatic islets in STZ-induced disease. Specific increases observed in TRAIL ligand and DcR1 expressions may be part of a defensive strategy of the beta islets against the infiltrating leukocytes, while the immune-suppressive agent CY may partly hold down this defense, contributing further to diabetes development.Ercument Dirice, Sevim Kahraman, Gulsum Ozlem Elpek, Cigdem Aydin, Mustafa Kemal Balci, Abdulkadir Omer, Salih Sanlioglu, and Ahter Dilsad SanliogluCopyright © 2011 Ercument Dirice et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/108328/Diabetic retinopathy, a vision-threatening disease, has been regarded as a vascular disorder. However, impaired oscillatory potentials (OPs) in the electroretinogram (ERG) and visual dysfunction are recorded before severe vascular lesions appear. Here, we review the molecular mechanisms underlying the retinal neural degeneration observed in the streptozotocin-(STZ-) induced type 1 diabetes model. The renin-angiotensin system (RAS) and reactive oxygen species (ROS) both cause OP impairment and reduced levels of synaptophysin, a synaptic vesicle protein for neurotransmitter release, most likely through excessive protein degradation by the ubiquitin-proteasome system. ROS also decrease brain-derived neurotrophic factor (BDNF) and inner retinal neuronal cells. The influence of both RAS and ROS on synaptophysin suggests that RAS-ROS crosstalk occurs in the diabetic retina. Therefore, suppressors of RAS or ROS, such as angiotensin II type 1 receptor blockers or the antioxidant lutein, respectively, are potential candidates for neuroprotective and preventive therapies to improve the visual prognosis.Yoko Ozawa, Toshihide Kurihara, Mariko Sasaki, Norimitsu Ban, Kenya Yuki, Shunsuke Kubota, and Kazuo TsubotaCopyright © 2011 Yoko Ozawa et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/848307/Emerging evidence suggests that dyslipidemia is an independent risk factor for diabetic neuropathy (DN) (reviewed by Vincent et al. 2009). To experimentally determine how dyslipidemia alters DN, we quantified neuropathic symptoms in diabetic mice fed a high-fat diet. Streptozotocin-induced diabetic C57BL/6 mice fed a high-fat diet developed dyslipidemia and a painful neuropathy (mechanical allodynia) instead of the insensate neuropathy (mechanical insensitivity) that normally develops in this strain. Nondiabetic mice fed a high-fat diet also developed dyslipidemia and mechanical allodynia. Thermal sensitivity was significantly reduced in diabetic compared to nondiabetic mice, but was not worsened by the high-fat diet. Moreover, diabetic mice fed a high-fat diet had significantly slower sensory and motor nerve conduction velocities compared to nondiabetic mice. Overall, dyslipidemia resulting from a high-fat diet may modify DN phenotypes and/or increase risk for developing DN. These results provide new insight as to how dyslipidemia may alter the development and phenotype of diabetic neuropathy.B. L. Guilford, J. M. Ryals, and D. E. WrightCopyright © 2011 B. L. Guilford et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/521076/Since the functional role(s) of angiotensin II (Ang II) type II receptor (AT2R) in type I diabetes is unknown, we hypothesized that AT2R is involved in decreasing the effects of type I diabetes on the kidneys. We induced diabetes with low-dose streptozotocin (STZ) in both AT2R knockout (AT2RKO) and wild-type (WT) male mice aged 12 weeks and followed them for 4 weeks. Three subgroups nondiabetic, diabetic, and insulin-treated diabetic (Rx insulin implant) were studied. Systolic blood pressure (SBP), physiological parameters, glomerular filtration rate (GFR), renal morphology, gene expression, and apoptosis were assessed. After 4 weeks of diabetes, compared to WT controls, AT2RKO mice clearly developed features of early diabetic nephropathy (DN), such as renal hypertrophy, tubular apoptosis, and progressive extracellular matrix (ECM) protein accumulation as well as increased GFR. AT2RKO mice presented hypertension unaffected by diabetes. Renal oxidative stress (measured as heme oxygenase 1 (HO-1) gene expression and reactive oxygen species (ROS) generation) and intrarenal renin angiotensin system components, such as angiotensinogen (Agt), AT1R, and angiotensin-converting enzyme (ACE) gene expression, were augmented whereas angiotensin-converting enzyme2 (ACE2) gene expression was decreased in renal proximal tubules (RPTs) of AT2RKO mice. The renal changes noted above were significantly enhanced in diabetic AT2RKO mice but partially attenuated in insulin-treated diabetic WT and AT2RKO mice. In conclusion, AT2R deficiency accelerates the development of DN, which appears to be mediated, at least in part, via heightened oxidative stress and ACE/ACE2 ratio in RPTs.Shiao-Ying Chang, Yun-Wen Chen, Isabelle Chenier, Stella Le Minh Tran, and Shao-Ling ZhangCopyright © 2011 Shiao-Ying Chang et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/486316/Growth in utero is largely a reflection of nutrient and oxygen supply to the foetus. We studied the effects of Mn restriction per se, maternal Mn restriction, and postnatal high-fat feeding in modulating body composition, lipid metabolism and adipocyte function in Wistar/NIN (WNIN) rat offspring. Female weanling, WNIN rats received ad libitum for 4 months, a control or Mn-restricted diet and were mated with control males. Some restricted mothers were rehabilitated with control diet from conception (MnRC) or parturition (MnRP), and their offspring were raised on control diet. Some restricted offspring were weaned onto control diet (MnRW), while others continued on restricted diet throughout (MnR). A set of offspring from each group was fed high-fat diet from 9 months onwards. Body composition, adipocytes function, and lipid metabolism were monitored in male rat offspring at regular intervals. Maternal manganese restriction increased the susceptibility of the offspring to high-fat-induced adiposity, dyslipidaemia, and a proinflammatory state but did not affect their glycemic or insulin status.Manisha Ganeshan, Pothaganti B. Sainath, Inagadapa J. Naga Padmavathi, Lagishetty Venu, Yedla Durga Kishore, Kalle Anand Kumar, Nemani Harishanker, J. Srinivasa Rao, and Manchala RaghunathCopyright © 2011 Manisha Ganeshan et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/976910/Objectives. To prospectively evaluate the technical feasibility and efficacy of wedged arterial injection (WAI) as a potential route for experimental selective therapy to the pancreas of healthy pigs. Materials and Methods. Selective angiographies were completed in ten pigs under general anaesthesia. By superselective angiography, the catheter was inserted and wedged into the major pancreatic artery, blocking the blood flow. In order to evaluate the efficacy of the WAI method, a DNA-specific fluorescent dye (Hoechst 33258) was used. Results. Histological study revealed a uniform distribution of the fluorescent dye within the nuclei of the endocrine and exocrine pancreatic cells. Pancreatic and liver enzymes as well as histopathology of the pancreas were normal. Conclusion. WAI is a highly effective minimally invasive methodology to target the porcine pancreas. The findings suggest that WAI may contribute to developing preclinical assays of pancreas gene or cell-transfer therapies in swine model.Rafael Latorre, Wendy Hernández, Fei Sun, Francisco Sánchez-Margallo, Francisco Gil, Octavio López-Albors, Jose M. Vázquez, and Jesús UsónCopyright © 2011 Rafael Latorre et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/481427/Exercise appears to improve glycemic control for people with type 1 diabetes (T1D). However, the mechanism responsible for this improvement is unknown. We hypothesized that exercise has a direct effect on the insulin-producing islets. Eight-week-old mice were divided into four groups: sedentary diabetic, exercised diabetic, sedentary control, and exercised control. The exercised groups participated in voluntary wheel running for 6 weeks. When compared to the control groups, the islet density, islet diameter, and β-cell proportion per islet were significantly lower in both sedentary and exercised diabetic groups and these alterations were not improved with exercise. The total insulin content and insulin secretion were significantly lower in sedentary diabetics compared to controls. Exercise significantly improved insulin content and insulin secretion in islets in basal conditions. Thus, some improvements in exercise-induced glycemic control in T1D mice may be due to enhancement of insulin content and secretion in islets.Han-Hung Huang, Kevin Farmer, Jill Windscheffel, Katie Yost, Mary Power, Douglas E. Wright, and Lisa Stehno-BittelCopyright © 2011 Han-Hung Huang et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/623472/Somatostatin acts via five receptors (sst1-5). We investigated if the changes in pancreatic islet sst expression in diabetic NOD mice compared to normoglycemic mice are a consequence of hyperglycemia or the ongoing immune reaction in the pancreas. Pancreatic islets were isolated from NOD mice precultured for 5 days and further cultured for 3 days at high or low glucose before examined. Islets were also isolated from NOD mice and transplanted to normal or diabetic mice in a number not sufficient to cure hyperglycemia. After three days, the transplants were removed and stained for sst1-5 and islet hormones. Overall, changes in sst islet cell expression were more common in islets cultured in high glucose concentration in vitro as compared to the islet transplantation in vivo to diabetic mice. The beta and PP cells exhibited more frequent changes in sst expression, while the alpha and delta cells were relatively unaffected by the high glucose condition. Our findings suggest that the glucose level may alter sst expressed in islets cells; however, immune mechanisms may counteract such changes in islet sst expression.Eva Ludvigsen, Mats Stridsberg, Eva T. Janson, and Stellan SandlerCopyright © 2011 Eva Ludvigsen et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/851280/During atherosclerosis monocyte-derived macrophages accumulate cholesteryl esters from low-density lipoproteins (LDLs) via lectin-like oxidised LDL receptor-1 (LOX-1) and class AI and AII (SR-AI, SR-AII) and class B (SR-BI, CD36) scavenger receptors. Here we examined the hypothesis that hyperglycaemia may modulate receptor expression and hence lipid accumulation in macrophages. Human monocytes were matured into macrophages in 30 versus 5 mM glucose and receptor expression and lipid accumulation quantified. High glucose elevated LOX1 mRNA, but decreased SR-AI, SR-BI, LDLR, and CD36 mRNA. SR-BI and CD36 protein levels were decreased. Normo- and hyperglycaemic cells accumulated cholesteryl esters from modified LDL to a greater extent than control LDL, but total and individual cholesteryl ester accumulation was not affected by glucose levels. It is concluded that, whilst macrophage scavenger receptor mRNA and protein levels can be modulated by high glucose, these are not key factors in lipid accumulation by human macrophages under the conditions examined.Fatemeh Moheimani, Joanne T. M. Tan, Bronwyn E. Brown, Alison K. Heather, David M. van Reyk, and Michael J. DaviesCopyright © 2011 Fatemeh Moheimani et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/192564/The impact of increased NF-κB-inducing kinase (NIK), a key component of the NF-κB activation pathways, on diabetes-induced renal inflammation remains unknown. We overexpressed NIK wild type (NIKwt) or kinase-dead dominant negative mutants (NIKdn) in HK-2 cells and demonstrated that RelB and p52, but not RelA, abundance and DNA binding increased in nuclei of NIKwt but not NIKdn overexpressed cells, and this corresponded with increases in multiple proinflammatory cytokines. Since TRAF3 negatively regulates NIK expression, we silenced TRAF3 by >50%; this increased nuclear levels of p52 and RelB, and transcript levels of proinflammatory cytokines and transcription factors. In HK-2 cells and mouse primary proximal tubule epithelial cells treated with methylglyoxal-modified albumin, multiple proinflammatory cytokines and NIK were increased in association with increased nuclear RelB and p52. These observations indicate that NIK regulates proinflammatory responses of renal proximal tubular epithelial cells via mechanisms involving TRAF3 and suggest a role for NF-κB noncanonical pathway activation in modulating diabetes-induced inflammation in renal tubular epithelium.Yanhua Zhao, Srijita Banerjee, Wanda S. LeJeune, Sanjeev Choudhary, and Ronald G. TiltonCopyright © 2011 Yanhua Zhao et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/810469/We sought to determine the effect of dipeptidyl peptidase IV (DPP-IV) inhibition on streptozotocin diabetes-induced vascular and neural dysfunction. After 4 weeks of untreated diabetes, rats were treated for 12 weeks with Alogliptin (DPP-IV inhibitor). Diabetes caused a slowing of motor and sensory nerve conduction velocity, thermal hypoalgesia, reduction in intraepidermal nerve fiber density in the hindpaw, and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles. Treatment significantly improved motor nerve conduction velocity and thermal response latency. Sensory nerve conduction velocity was marginally improved with treatment of diabetic rats, and treatment did not improve the decrease in intraepidermal nerve fiber density. Vascular relaxation by epineurial arterioles to calcitonin gene-related peptide but not acetylcholine was significantly improved with treatment. These studies suggest that some but not all vascular and neural complications associated with type 1 diabetes can be improved with the inhibition of DPP-IV activity.Eric P. Davidson, Lawrence J. Coppey, Brian Dake, and Mark A. YorekCopyright © 2011 Eric P. Davidson et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/978762/Background. Role of herbs in the management and control of diabetes has emerged fast over the years. We assessed the efficacy of Coccinia grandis (locally known as Ken, Kovakka) leaves as a hypoglycemic agent. Methods. Double-blind phase I clinical trial was conducted at the general hospital and a private hospital in Matara in August 2009. All the participants were given a common meal for dinner, and they maintained a 10-hour fasting period. Sixty-one healthy volunteers were given a meal containing 20 g of leaves of Coccinia grandis which was mixed with a measured amount of scraped coconut and table salt for breakfast, and other 61 were given the placebo meal which also contained scraped coconut and salt. Glucose tolerance test was performed blindly for the two groups. Mixed factorial design analysis of variance and student's t-test were applied. Results. Overall blood sugar levels of the experimental group were also significantly lower than those of the control group (F(1,117) 5.56, P<0.05). Increase in the blood sugar levels from fasting to one hour (F(1,117) 6.77, P<0.05) and two hours (F(1,117) 5.28, P<0.05) postprandially was statistically significant for participants who were in the control group than those of in the experimental group. The mean difference of postprandial blood sugar levels (mg/dL) after one hour (20.2, 95% confidence interval, 4.81 to 35.5) and two hours (11.46, 95% confidence interval; 1.03 to 21.9) was statistically significant between the two groups. Conclusions. Coccinia grandis has a blood sugar lowering effect. However further studies are needed to validate our findings.M. A. A. K. Munasinghe, C. Abeysena, I. S. Yaddehige, T. Vidanapathirana, and K. P. B. PiyumalCopyright © 2011 M. A. A. K. Munasinghe et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/835932/To evaluate the sympathetic innervation of the female diabetic heart, resting heart rate and sympathetic tone were assessed in vivo, and effect of tyramine on spontaneous beating rate, norepinephrine atrial concentrations, uptake, and release were determined in vitro in streptozotocin- (STZ-) treated rats and respective controls aged 3 months to 2 years. Resting bradycardia, decreased sympathetic tone, deceleration of spontaneous beating rate, and slightly declining carrier-mediated, but preserved exocytotic norepinephrine release from the atria were found in younger diabetic rats while the reactivity of the right atria to tyramine was not affected with age and disease duration. Diabetic two-year-old animals displayed symptoms of partial spontaneous recovery including normoglycemia, increased plasma insulin concentrations, fully recovered sympathetic tone, but putative change, in releasable norepinephrine tissue stores. Our data suggested that female diabetic heart exposed to long-lasting diabetic conditions seems to be more resistant to alteration in sympathetic innervation than the male one.Jitka Švíglerová, Jiří Mudra, Zbyněk Tonar, Jana Slavíková, and Jitka KuncováCopyright © 2011 Jitka Švíglerová et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/421982/The tail-anchored membrane protein, sarcolemmal membrane associated protein (SLMAP) is encoded to a single gene that maps to the chromosome 3p14 region and has also been reported in certain diabetic populations. Our previous studies with db/db mice shown that a deregulation of SLMAP expression plays an important role in type 2 diabetes. Male Tally Ho mice were bred to present with either normoglycemia (NG) or hyperglycemia (HG). Abdominal adipose tissue from male Tally Ho mice of the HG group was found to have a significantly lower expression of the membrane associated glucose transporter-4 (GLUT-4) and higher expression of SLMAP compared to tissue from NG mice. There were 3 isoforms expressed in the abdominal adipose tissue, but only 45 kDa isoform of SLMAP was associated with the GLUT-4 revealed by immunoprecipitation data. Knock down studies using SLMAP siRNA with adipocytes resulted in a significant reduction in SLMAP and a decrease in glucose uptake. Thus, SLMAP may be an important regulator of glucose uptake or involved in GLUT-4 fusion/translocation into the plasma membrane of mouse abdominal adipose tissue and changes in SLMAP expression are linked to hyperglycemia and diabetes.Xiaoliang Chen and Hong DingCopyright © 2011 Xiaoliang Chen and Hong Ding. All rights reserved.http://www.hindawi.com/journals/edr/2011/910159/Patients treated with recombinant human Epo demonstrate an improvement in insulin sensitivity. We aimed to investigate whether CNTO 530, a novel Epo receptor agonist, could affect glucose tolerance and insulin sensitivity. A single administration of CNTO 530 significantly and dose-dependently reduced the area under the curve in a glucose tolerance test in diet-induced obese and diabetic mice after 14, 21, and 28 days. HOMA analysis suggested an improvement in insulin sensitivity, and this effect was confirmed by a hyperinsulinemic-euglycemic clamp. Uptake of 14C-2-deoxy-D-glucose indicated that animals dosed with CNTO 530 transported more glucose into skeletal muscle and heart relative to control animals. In conclusion, CNTO530 has a profound effect on glucose tolerance in insulin-resistant rodents likely because of improving peripheral insulin sensitivity. This effect was observed with epoetin-α and darbepoetin-α, suggesting this is a class effect, but the effect with these compounds relative to CNTO530 was decreased in duration and magnitude.Michael S. Scully, Tatiana A. Ort, Ian E. James, Peter J. Bugelski, Dorie A. Makropoulos, Heather A. Deutsch, Elsbet J. Pieterman, Anita M. van den Hoek, Louis M. Havekes, William H. duBell, Joshua D. Wertheimer, and Kristen M. PichaCopyright © 2011 Michael S. Scully et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/947138/The aim of this study is to explore the mechanisms by which electroacupuncture (EA) enhances the hypoglycemic effect of exogenous insulin in a streptozotocin- (STZ-) diabetic rats. Animals in the EA group were anesthetized and subjected to the insulin challenge test (ICT) and EA for 60 minutes. In the control group, rats were subjected to the same treatment with the exception of EA stimulation. Blood samples were drawn to measure changes in plasma glucose, free fatty acids (FFA), and insulin levels. Western blot was used to assay proteins involved in insulin signaling. Furthermore, atropine, hemicholinium-3 (HC-3), and Eserine were used to explore the relationship between EA and cholinergic nerve activation during ICT. EA augmented the blood glucose-lowering effects of EA by activating the cholinergic nerves in STZ rats that had been exposed to exogenous insulin. This phenomenon may be related to enhancement of insulin signaling rather than to changes in FFA concentration.Yu-Chen Lee, Te-Mao Li, Chung-Yuh Tzeng, Yu-Wen Cheng, Ying-I Chen, Wai-Jane Ho, Jaung Geng Lin, and Shih-Liang ChangCopyright © 2011 Yu-Chen Lee et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/907496/In recent years, evidence has been accumulated that metformin, an antidiabetic drug in the biguanide class, in addition to its well-recognized glucose-lowering effect, can also reduce cardiovascular mortality in the patients with type 2 diabetes mellitus (T2DM). Besides, there are a few experimental studies on the possibility of the direct anti-ischemic effect of the drug in both type 1 diabetes mellitus and T2DM. In our study, myocardial tolerance to ischemia in rats with neonatal streptozotocin T2DM was investigated using the model of global ischemia-reperfusion of the isolated perfused heart. Metformin was administered i.p. at a dose of 200 mg/kg/day for 3 days prior to isolated heart perfusion. The results showed that both the infarct size and postischemic recovery of left ventricular function were not different between controls and metformin-treated animals. At the same time, the infarct size in the T2DM animals was significantly lower than that in the controls (24.4 ± 7.6% versus 45.0 ± 10.4%, resp., P<.01), indicative of the metabolic preconditioning in T2DM. It follows that the protocol of metformin administration used in this study had not elicited cardioprotective effect in animals with T2DM so that the different mechanism(s) may underlie the beneficial effect of metformin on cardiovascular complications in patients with T2DM which, however, would need further investigation.Ekaterina Kravchuk, Elena Grineva, Alekber Bairamov, Michael Galagudza, and Timur VlasovCopyright © 2011 Ekaterina Kravchuk et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/853501/TGR5, an emerging G protein-coupled receptor, was identified as a membrane receptor for bile acids. The expression of TGR5 and its function are distinct from the previously identified nuclear bile acid receptor, farnesoid X receptor (FXR). These two bile acid receptors complement with each other for maintaining bile acid homeostasis and mediating bile acid signaling. Both receptors are also shown to play roles in regulating inflammation and glucose metabolism. An interesting finding for TGR5 is its role in energy metabolism. The discovery of TGR5 expression in brown adipocyte tissues (BATs) and the recent demonstration of BAT in adult human body suggest a potential approach to combat obesity by targeting TGR5 to increase thermogenesis. We summarize here the latest finding of TGR5 research, especially its role in energy metabolism and glucose homeostasis.Xiaosong Chen, Guiyu Lou, Zhipeng Meng, and Wendong HuangCopyright © 2011 Xiaosong Chen et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/754673/To investigate the effect of intermittent high glucose (IHG) and sustained high glucose (SHG) on inducing β-cell apoptosis and the potential involved mechanisms, INS-1 beta cells were incubated for 72 h in the medium containing different glucose concentrations: control (5.5 mmol/L), SHG (33.3 mmol/L), and IHG (5.5 mmol/L and 33.3 mmol/L glucose alternating every 12 h). Cell viability, apoptosis rate, and oxidative-stress markers were determined. The results showed that the apoptosis induced by IHG was more obvious than that by SHG. Simultaneously, the intracellular level of oxidative stress was more significantly increased in INS-1 cells exposed to IHG. These findings suggest that intermittent high glucose could be more deleterious to β-cell than a constant high concentration of glucose, this may be due to the aggravation of oxidative stress triggered by intermittent high glucose.Xiao-li Shi, Yue-zhong Ren, and Jing WuCopyright © 2011 Xiao-li Shi et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/498460/A small portion of Type 2 diabetes mellitus (T2DM) is familial, but the majority occurs as sporadic disease. Although causative genes are found in some rare forms, the genetic basis for sporadic T2DM is largely unknown. We searched for a copy number abnormality in 100 early-onset Japanese T2DM patients (onset age <35 years) by whole-genome screening with a copy number variation BeadChip. Within the 1.3-Mb subtelomeric region on chromosome 4p16.3, we found copy number losses in early-onset T2DM (13 of 100 T2DM versus one of 100 controls). This region surrounds a genome gap, which is rich in multiple low copy repeats. Subsequent region-targeted high-density custom-made oligonucleotide microarray experiments verified the copy number losses and delineated structural changes in the 1.3-Mb region. The results suggested that copy number losses of the genes in the deleted region around the genome gap in 4p16.3 may play significant roles in the etiology of T2DM.Hirohito Kudo, Mitsuru Emi, Yasushi Ishigaki, Uiko Tsunoda, Yoshinori Hinokio, Miho Ishii, Hidenori Sato, Tetsuya Yamada, Hideki Katagiri, and Yoshitomo OkaCopyright © 2011 Hirohito Kudo et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/406182/Diabetes mellitus is a chronic disease with many debilitating complications. Treatment of diabetes mellitus mainly revolves around conventional oral hypoglycaemic agents and insulin replacement therapy. Recently, scientists have turned their attention to the generation of insulin-producing cells (IPCs) from stem cells of various sources. To date, many types of stem cells of human and animal origins have been successfully turned into IPCs in vitro and have been shown to exert glucose-lowering effect in vivo. However, scientists are still faced with the challenge of producing a sufficient number of IPCs that can in turn produce sufficient insulin for clinical use. A careful choice of stem cells, methods, and extrinsic factors for induction may all be contributing factors to successful production of functional beta-islet like IPCs. It is also important that the mechanism of differentiation and mechanism by which IPCs correct hyperglycaemia are carefully studied before they are used in human subjects.Rebecca S. Y. WongCopyright © 2011 Rebecca S. Y. Wong. All rights reserved.http://www.hindawi.com/journals/edr/2011/212571/Insulin signaling depends on tyrosine phosphorylation of insulin receptor substrates (IRSs) to mediate downstream effects; however, elevated serine phosphorylation of IRS impairs insulin signaling. Here, we investigated IRS protein expression patterns in dorsal root ganglia (DRG) of mice and whether their signaling was affected by diabetes. Both IRS1 and IRS2 are expressed in DRG; however, IRS2 appears to be the prevalent isoform and is expressed by many DRG neuronal subtypes. Phosphorylation of Ser(731)IRS2 was significantly elevated in DRG neurons from type 1 and type 2 diabetic mice. Additionally, Akt activation and neurite outgrowth in response to insulin were significantly decreased in DRG cultures from diabetic ob/ob mice. These results suggest that DRG neurons express IRS proteins that are altered by diabetes similar to other peripheral tissues, and insulin signaling downstream of the insulin receptor may be impaired in sensory neurons and contribute to the pathogenesis of diabetic neuropathy.C. W. Grote, J. K. Morris, J. M. Ryals, P. C. Geiger, and D. E. WrightCopyright © 2011 C. W. Grote et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/374943/We have established spontaneously immortalized Schwann cell lines from normal adult mice and rats and murine disease models. One of the normal mouse cell lines, IMS32, possesses some biological properties of mature Schwann cells and high proliferative activities. The IMS32 cells under hyperglycemic and/or hyperlipidemic conditions have been utilized to investigate the pathogenesis of diabetic neuropathy, especially the polyol pathway hyperactivity, glycation, increased oxidative stress, and reduced synthesis of neurotrophic factors. In addition to the mouse cell lines, our current study focuses on the characterization of a normal rat cell line, IFRS1, under normal and high glucose conditions. These Schwann cell lines can be valuable tools for exploring the detailed mechanisms leading to diabetic neuropathy and novel therapeutic approaches against that condition.Kazunori Sango, Hiroko Yanagisawa, Shizuka Takaku, Emiko Kawakami, and Kazuhiko WatabeCopyright © 2011 Kazunori Sango et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/693426/Diabetic retinopathy (DR) is the most severe of the several ocular complications of diabetes, and in the United States it is the leading cause of blindness among adults 20 to 74 years of age. Despite recent advances in our understanding of the pathogenesis of DR, there is a pressing need to develop novel therapeutic treatments that are both safe and efficacious. In the present paper, we identify a key mechanism involved in the development of the disease, namely, the interaction between neuronal and vascular activities. Numerous pathological conditions in the CNS have been linked to abnormalities in the relationship between these systems. We suggest that a similar situation arises in the diabetic retina, and we propose a logical strategy aimed at therapeutic intervention.Haohua Qian and Harris RippsCopyright © 2011 Haohua Qian and Harris Ripps. All rights reserved.http://www.hindawi.com/journals/edr/2011/269378/Microalbuminuria in humans with Type 1 diabetes (T1D) is associated with increased urinary excretion of megalin, as well as many megalin ligands, including vitamin-D-binding protein (VDBP). We examined the DBA/2J diabetic mouse, nephropathy prone model, to determine if megalin and VDBP excretion coincide with the development of diabetic nephropathy. Megalin, VDBP, and 25-hydroxy-vitamin D (25-OHD) were measured in urine, and genes involved in vitamin D metabolism were assessed in renal tissues from diabetic and control mice at 10, 15, and 18 weeks following the onset of diabetes. Megalin, VDBP, and 25-OHD were increased in the urine of diabetic mice. 1-α hydroxylase (CYP27B1) mRNA in the kidney was persistently increased in diabetic mice, as were several vitamin D-target genes. These studies show that intrarenal vitamin D handling is altered in the diabetic kidney, and they suggest that in T1D, urinary losses of VDBP may portend risk for intrarenal and extrarenal vitamin D deficiencies.John L. Fowlkes, R. Clay Bunn, Gael E. Cockrell, Lindsey M. Clark, Elizabeth C. Wahl, Charles K. Lumpkin, and Kathryn M. ThrailkillCopyright © 2011 John L. Fowlkes et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/710635/The rice fermented by Monascus, called red mold rice (RMR), and has a long tradition in East Asia as a dietary staple. Monascus-fermented dioscorea called red mold dioscorea (RMD) contains various metabolites to perform the ability of reducing oxidative stress and anti-inflammatory response. We used Wistar rats and induced diabetes by injecting streptozotocin (STZ, 65 mg/kg i.p.). RMD was administered daily starting six weeks after disease onset. Throughout the experimental period, significantly (P<.05) lowered plasma glucose, triglyceride, cholesterol, free fatty acid and low density lipoprotein levels were observed in the RMD-treated groups. The RMD-treated diabetic rats showed higher activities of glutathione disulfide reductase, glutathione reductase, catalase and superoxide dismutase (P<.05) in the pancreas compared with the diabetic control rats. RMD also inhibited diabetes-induced elevation in the levels of interleukin (IL)-1β, IL-6, interferon-γ and tumor necrosis factor-α. Pancreatic β-cells damaged by STZ in the RMD supplemented groups were ameliorated. The results of this study clearly demonstrated that RMD possesses several treatment-oriented properties, including the control of hyperglycemia, antioxidant effects, pancreatic β-cell protection and anti-inflammatory effects. Considering these observations, it appears that RMD may be a useful supplement to delay the development of diabetes and its complications.Yeu-Ching Shi, Jiunn-Wang Liao, and Tzu-Ming PanCopyright © 2011 Yeu-Ching Shi et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/527520/Aims. The SLC2A9 gene encodes the glucose transporter 9, with the abilities of transporting both glucose and uric acid and is involved in the pancreatic glucose-stimulated insulin secretion. The single nucleotide polymorphisms (SNPs) of SLC2A9 accounted for 5% variance of serum uric acid (UA). UA was identified as a risk factor for type 2 diabetes mellitus (DM). We investigated whether the SLC2A9 gene variations are associated with type 2 DM in Han Chinese. Methods. Three common SNPs of the SLC2A9, rs1014290, rs2280205, and rs3733591, were genotyped in 1003 Han Chinese randomly selected from Kaohsiung, Taiwan. Results. The variant SNP rs1014290 is associated with decreased 0.12-fold risk of type 2 DM (P=.002). Per-copy increase in the minor C-allele results in 0.13 mmol/L (P=.037) and 10.03 μmol/L (P=.016) decrease in serum glucose and UA, respectively. Conclusions. The SNP rs1014290 within the SLC2A9 gene is associated with type 2 DM in Han Chinese.Wan-Chun Liu, Chi-Chih Hung, Szu-Chia Chen, Ming-Yen Lin, Ling-I Chen, Daw-Yang Hwang, Jer-Ming Chang, Jer-Chia Tsai, Hung-Chun Chen, and Shang-Jyh HwangCopyright © 2011 Wan-Chun Liu et al. All rights reserved.http://www.hindawi.com/journals/edr/2011/928523/High fat feeding induces a variety of obese and lean phenotypes in inbred rodents. Compared to Diet Resistant (DR) rodents, Diet Induced Obese (DIO) rodents are insulin resistant and have a reduced dopamine receptor D2 (DRD2) mediated tone. We hypothesized that this differing dopaminergic tone contributes to the distinct metabolic profiles of these animals. C57Bl6 mice were classified as DIO or DR based on their weight gain during 10 weeks of high fat feeding. Subsequently DIO mice were treated with the DRD2 agonist bromocriptine and DR mice with the DRD2 antagonist haloperidol for 2 weeks. Compared to DR mice, the bodyweight of DIO mice was higher and their insulin sensitivity decreased. Haloperidol treatment reduced the voluntary activity and energy expenditure of DR mice and induced insulin resistance in these mice. Conversely, bromocriptine treatment tended to reduce bodyweight and voluntary activity, and reinforce insulin action in DIO mice. These results show that DRD2 activation partly redirects high fat diet induced metabolic anomalies in obesity-prone mice. Conversely, blocking DRD2 induces an adverse metabolic profile in mice that are inherently resistant to the deleterious effects of high fat food. This suggests that dopaminergic neurotransmission is involved in the control of metabolic phenotype.J. E. de Leeuw van Weenen, E. T. Parlevliet, J. P. Schröder-van der Elst, S. A. van den Berg, K. Willems van Dijk, J. A. Romijn, and H. PijlCopyright © 2011 J. E. de Leeuw van Weenen et al. All rights reserved.