Non-fasting Blood Glucose Levels Research Articles

Development of Novel Gastroretentive Floating Particulate Drug Delivery System of Gliclazide

The objective of present project was to improve the dissolution profile of gliclazide by developing floating alginate beads using various biodegradable polymers like gelatin, pectin and hydroxypropylmethylcellulose (HPMC). The floating beads were prepared by a simple ionotropic gelatin method using calcium carbonate as gas generating agent. The developed beads were characterized by Fourier transform infrared spectroscopy analysis, differential scanning calorimetry, X-ray diffraction analysis and scanning electron microscopy (SEM). The prepared beads showed good in vitro floatation, which was dependent on the concentration of gas-forming agent. SEM photomicrographs confirmed that the developed beads were spherical in shape and had particle size in the range of 730 to 890 μm. The incorporation efficiency was found to be in the range of 59.96 to 85.1%. The cumulative percent drug release from the beads after 10 h dissolution study at pH 1.2 and pH 5.8 was in the range of 33 to 46% and 82 to 95% respectively. The concentration of the gas generating agent was found to influence the release rate. The mechanism of drug release was Fickian diffusion with swelling. The in vivo sub-acute hypoglycemic study in high fat diet induced diabetic C57BL/6J mice demonstrated significant (p < 0.05) hypoglycemic effect over a period of 12 h and 24 h, respectively, with HPMC and pectin beads. A significant (p & 0.05) reduction in fasting and non-fasting blood glucose levels, reduction in fasting plasma insulin level and a significant improvement in glucose tolerance were observed in animals treated with formulations. The developed beads were suitable carriers for improving the systemic absorption of gliclazide and maintaining reduced blood glucose levels.

Effects of Xylitol on Blood Glucose, Glucose Tolerance, Serum Insulin and Lipid Profile in a Type 2 Diabetes Model of Rats

Background/Aims: The present study was conducted to examine the antidiabetic effects of xylitol in a type 2 diabetes rat model. Methods: Six-week-old male Sprague-Dawley rats were randomly divided into 3 groups: normal control (NC), diabetic control (DBC) and xylitol (XYL). Diabetes was induced only in the DBC and XYL animal groups by feeding them a 10% fructose solution for 2 weeks followed by an injection (i.p.) of streptozotocin (40 mg/kg body weight). One week after the streptozotocin injection, the animals with a nonfasting blood glucose level of >300 mg/dl were considered to be diabetic. The XYL group was fed further with a 10% xylitol solution, whereas the NC and DBC groups were supplied with normal drinking water. Results: After 5 weeks of intervention, food and fluid intake, body weight, blood glucose, serum fructosamine and most of the serum lipids were significantly decreased, and serum insulin concentration and glucose tolerance ability was significantly increased in the XYL group compared to the DBC group. Liver weight, liver glycogen and serum triglycerides were not influenced by feeding with xylitol. Conclusion: The data of this study suggest that xylitol can be used not only as a sugar substitute but also as a supplement to antidiabetic food and other food products.

Increase in Insulin Secretion Induced by Panax ginseng Berry Extracts Contributes to the Amelioration of Hyperglycemia in Streptozotocin-induced Diabetic Mice

Panax ginseng has long been used as a traditional herbal medicine. More recently, it has received attention for its anti-diabetic and anti-obesity effects in humans and in animal models of type 2 diabetes. In the present study, we tested the hypoglycemic effects of ginseng berry extract in beta-cell-deficient mice and investigated the mechanisms involved. Red (ripe) and green (unripe) berry extracts were prepared and administered orally (100 or 200 mg/kg body weight) to streptozotocin-induced diabetic mice daily for 10 wk. The body weight was measured daily, and the nonfasting blood glucose levels were measured after 5 and 10 wk after administration. Glucose tolerance tests were performed, and the serum insulin levels were measured. The proliferation of betacells was measured in vitro. The administration of red or green ginseng berry extract significantly reduced the blood glucose levels and improved the glucose tolerance in beta-cell deficient mice, with the higher doses resulting in better effects. Glucose-stimulated insulin secretion was significantly increased in berry extract-treated mice compared with streptozotocin-induced diabetic control mice. Treatment with ginseng berry extract increased beta-cell proliferation in vitro. Both red berry and green berry extracts improved glycemic control in streptozotocin-induced diabetic mice and increased insulin secretion, possibly due to increased beta-cell proliferation. These results suggest that ginseng berry extracts might have beneficial effects on beta-cell regeneration.

Synthesis and evaluation of piperidine urea derivatives as efficacious 11β-hydroxysteroid dehydrogenase type 1 inhibitors in diabetic ob/ob mice

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) has attracted considerable attention as a potential target for the treatment of diabetes and metabolic syndrome. Herein we report the design, synthesis and efficacy evaluation of novel amide and urea 11β-HSD1 inhibitors. Structure–activity relationship studies led to the identification of 10c, which was efficacious in a diabetic ob/ob mouse model and reduced fasting and non-fasting blood glucose levels after ip dosing.

Difference in glucose intolerance between C57BL/6J and ICR strain mice with streptozotocin/nicotinamide-induced diabetes

Blood glucose and plasma insulin levels between C57BL/6J and ICR strain mice with nicotinamide (NA) and streptozotocin (STZ)-induced diabetes were compared to establish a suitable strain of the experimental diabetic mouse model. The mice were intraperitoneally treated twice with STZ (100 mg/kg) 15 min after injection of NA (120 mg/kg) at a 1-day interval, and non-fasting blood glucose level was then weekly monitored for 5 weeks. The blood glucose level in ICR mice gradually increased and was about 2-times higher than that in C57BL/6J mice at the end of the observation. The plasma insulin level in ICR mice was comparatively low, compared with that in C57BL/6J mice. ICR mice were also markedly glucose-intolerant when oral glucose tolerance test was performed. These results indicate that ICR strain is more sensitive than C57BL/6J strain as a mouse model with NA/STZ-induced mild diabetes.

Fructose-fed streptozotocin-injected rat: an alternative model for type 2 diabetes

The main objective of the study was to develop an alternative non-genetic rat model for type 2 diabetes (T2D). Six-week-old male Sprague-Dawley rats (190.56±23.60 g) were randomly divided into six groups, namely: Normal Control (NC), Diabetic Control (DBC), Fructose-10 (FR10), Fructose-20 (FR20), Fructose-30 (FR30) and Fructose-40 (FR40) and were fed a normal rat pellet diet ad libitum for 2 weeks. During this period, the two control groups received normal drinking water whilst the fructose groups received 10, 20, 30 and 40% fructose in drinking water ad libitum, respectively. After two weeks of dietary manipulation, all groups except the NC group received a single injection (ip) of streptozotocin (STZ) (40mg/kg b.w.) dissolved in citrate buffer (pH 4.4). The NC group received only a vehicle buffer injection (ip). One week after the STZ injection, animals with non-fasting blood glucose levels > 300mg/dl were considered as diabetic. Three weeks after the STZ injection, the animals in FR20, FR30 and FR40 groups were eliminated from the study due to the severity of diabetes and the FR10 group was selected for the remainder of the 11 weeks experimental period. The significantly (p<0.05) higher fluid intake, blood glucose, serum lipids, liver glycogen, liver function enzymes and insulin resistance (HOMA-IR) and significantly (p<0.05) lower body weight, oral glucose tolerance, number of pancreatic β-cells and pancreatic β-cell functions (HOMA-β) of FR10 group demonstrate that the 10% fructose-fed followed by 40mg/kg of BW STZ injected rat can be a new and alternative model for T2D.

Vitamin D and Metabolic Syndrome in Immigrant East Asian Women Living in Sydney, Australia: A Pilot

Background: As epidemiological studies have linked vitamin D deficiency to risk of metabolic syndrome, we investigated vitamin D deficiency with metabolic syndrome prevalence in immigrant Asian women. Materials and Methods: In a cross-sectional pilot survey of older East Asian women (n=85 aged 60-95) we examined the association between vitamin D status (measured by serum 25-hydroxyvitamin D) with metabolicsyndrome risk factors. Results: The population mean for 25-hydroxyvitamin D concentration in serum was 56 ± 22 nmol/L with forty percent being vitamin D deficient (< 50 nmol/L). Ninety-eight percent of the population had at least one metabolic syndrome risk factor, 85% had two, 55% had three and 8% had four. Having four metabolic syndrome risk factors was associated with a three fold risk of vitamin D deficiency. Vitamin D deficiency was associated with high non-fasting blood glucose levels ≥7.7 mmol/L (OR=5.2, 95%CI=1.8-18) and non-significantly, with being overweight (OR=1.8, 95%CI =0.7-5). In contrast, vitamin D deficiency was not associated with either hypertension or central obesity. Environmental factors associated with vitamin D deficiency in these data were no vitamin tablet intake (calcium or vitamin D) (OR=7.2, 95%CI=1.8-29; OR=6.3, 95%CI=1.2-32, respectively); not being acculturated to an Australian lifestyle, (OR=2.6, 95%CI=0.9-8) or less sun exposure on the weekends (OR=3.6, 95%CI=1.0-13). After adjustment for these predictors, if these Asian immigrants were vitamin D deficient they were at an eight fold risk of having high blood glucose measurements (OR=7.6, 95%CI=1-53). Conclusion: Further larger prospective studies should be conducted to examine the association between vitamin D deficiency and risk of metabolic syndrome in similar immigrant populations.

Effect of chronic intracerebroventricular insulin administration in rats on the peripheral glucose metabolism and synaptic plasticity of CA1 hippocampal neurons

In this study we examined the effects of sustained intracerebroventricular insulin infusion on hippocampal synaptic plasticity in rats. Insulin was infused intracerebroventricularly in male Wistar rats (n=12) for 3months using osmotic minipumps. A control group (n=12) received a sham operation. Insulin infusion led to an initial reduction in food intake and body weight gain, but these differences attenuated over 12weeks. Insulin infusion did not affect fasting or non-fasting blood glucose levels. Field synaptic potentials recording from the hippocampus demonstrated a defect in the expression of long-term potentiation. Sharp electrode current-clamp recording showed that CA1 pyramidal cells fire action potentials in response to prolonged depolarizing current injection and those action potentials showed progressive broadening. The action potential broadening in the insulin-perfused animals were significantly longer than the control. The amplitude of slow after hyperpolarization (sAHP) was measured after manually “clamping” the cells at −65mV and injecting currents to evoke a train of four APs. The sAHP amplitude was significantly longer than in the control animals. We conclude that local insulin infusion into the brain of rats had significant effects on synaptic plasticity in the absence of marked effects on systemic glucose levels. These results indicate that long-term elevation of insulin levels can have adverse effects directly on the brain.

AEB071 (sotrastaurin) does not exhibit toxic effects on human islets in vitro nor after transplantation into immunodeficient mice

AEB071 (AEB, sotrastaurin), a specific inhibitor of protein kinase C, reduces T-lymphocyte activation and cytokine release. AEB delays islet allograft rejection in rats, and prevents rejection when combined with cyclosporine. Since many immunosuppressive agents have toxic effects on the function of transplanted islets, we investigated whether this was also the case with AEB. Human islets were transplanted into Rag-knockout mice randomly assigned to vehicle control, AEB, or sirolimus treatment groups. Non-fasting blood glucose levels, body weight, and glucose tolerance was measured in recipients. In a separate experiment, human islets were cultured in the presence of AEB and assayed for glucose dependent insulin secretion and level of β-cell apoptosis. Eighty-six percent of the AEB-treated recipients achieved normoglycemia following transplant (compared with none in sirolimus-treated group, p < 0.05). AEB-treated recipients exhibited similar glucose homeostasis as vehicle-treated controls, which was better than in sirolimus-treated recipients. Human islets cultured with AEB showed similar rates of β-cell apoptosis (p = 0.98 by one-way ANOVA) and glucose stimulated insulin secretion (p = 0.15) as those cultured with vehicle. These results suggest that AEB is not associated with toxic effects on islet engraftment or function. AEB appears to be an appropriate immunosuppressive candidate for clinical trials in islet transplantation.

Antidiabetic Activities of Extract from Malva verticillata Seed via the Activation of AMP-Activated Protein Kinase

Stimulation of AMP-activated protein kinase (AMPK) signaling followed by increase of glucose uptake in L6 myotubes were studied with organic solvent extract of Malva verticillata (MV) seeds. Ethanol extract of M. verticillata seeds (MVE) significantly increased the phosphorylation level of AMPK, acetyl-CoA carboxylase (ACC), and glucose uptake in L6 myotube cells. The MVE was fractionated with n-hexane (MVE-H), chloroform (MVE-C), ethylacetate (MVE-E), n-butanol (MVE-B), and water (MVE-W). MVE-H (150 microgram/ml) showed the highest phosphorylating activity and increased glucose uptake by 2.3-fold. Oral administration of MVE-H (40 mg/kg) for 4 weeks to type 2 diabetic (db/db) mice reduced non-fasting and fasting blood glucose levels by 17.1% and 23.3%, respectively. Phosphorylation levels of AMPK and ACC in the soleus muscle and liver tissue of db/db mice were significantly increased by the administration of MVE-H. MVE-H was further fractionated using preparative HPLC to identify the AMPK-activating compounds. The NMR and GC-MS analyses revealed that β-sitosterol was a major effective compound in MVE-H. Phosphorylation levels of AMPK and ACC, and glucose uptake were significantly increased by the treatment of MVE-S (β-sitosterol) isolated from M. verticillata to L6 cells, and these effects were attenuated by an AMPK inhibitor (Compound C) pretreatment. These results, taken together, demonstrate that increased glucose uptake in L6 myotubes by MVE-H treatment is mainly accomplished through the activation of AMPK. Our finding suggests that the extract isolated from M. verticillata seed would be beneficial for the treatment of metabolic disease including type 2 diabetes and hyperlipidemia.

Tracing of islet graft survival by way of in vivo fluorescence imaging

To increase the success rate in xenogeneic islet transplantation, proper assessment of graft mass is required following transplantation. For this reason, we aimed to develop a suitable fluorescence imaging system to monitor islet xenograft survival in diabetic mice. Adenovirus vector encoding enhanced green fluorescent protein-transduced rat pancreatic islets were transplanted under the renal capsule of streptozotocin-induced diabetic mice and the fluorescence signal was quantified over time using a cooled charge-coupled device. Non-fasting blood glucose levels were recorded during the same period. Insulin release from transduced and control islets was detected via enzyme-linked immunosorbent assay. Adenovirus vector encoding enhanced green fluorescent protein infection did not alter the function or survival of pancreatic islets post transduction. A direct correlation was found between the number of islets (250-750) transplanted under the kidney capsule and the blood glucose recovery. Fluorescence imaging appears to be a useful tool for quantitative assessment of islet cell viability post transplantation and could permit earlier detection of graft rejection.

Regulatory mechanism for the stimulatory action of genistein on glucose uptake in vitro and in vivo

Genistein, an isoflavone, is known to possess diverse biological functions such as antioxidative and anti-inflammatory actions. It also acts like estrogen and inhibits several tyrosine kinases. Genistein was reported to suppress insulin-mediated glucose uptake in adipocytes. In this study, we investigated the effects of genistein on glucose uptake in vitro and in vivo as well as the mechanisms associated with the glucose uptake. We found that genistein decreased nonfasting blood glucose levels in KK-Ay/Ta Jcl mice, a type 2 diabetic animal model. It also dose-dependently induced insulin secretion by Rin-5F cells. In L6 myotubes, it directly stimulated glucose uptake independently of insulin under normal and high glucose conditions in dose-dependent manners. It promoted the translocation of glucose transporter 4 to the cell membrane under both glucose conditions. Based on studies using inhibitors of signaling molecules related to glucose uptake, the stimulatory effect of genistein on glucose uptake appeared to be dependent on the phosphatidylinositol 3-kinase, mammalian target of rapamycin, protein kinase C and 5'-adenosine-monophosphate-activated protein kinase pathway under both glucose conditions. In addition, O-GlcNAcylation by O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino N-phenyl carbamate, an inhibitor of N-acetylglucosaminidase, reduced the stimulatory effect of genistein on glucose uptake under both glucose conditions. Taken together, genistein may regulate glucose uptake by increasing the phosphorylation and decreasing the O-GlcNAcylation of proteins related to glucose homeostasis.

Treatment with the α-glucosidase inhibitor miglitol from the preonset stage in Otsuka Long-Evans Tokushima Fatty rats improves glycemic control and reduces the expression of inflammatory cytokine genes in peripheral leukocytes

Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes mellitus, exhibit chronic and slowly progressive hyperglycemia with obesity. In this study, we examined whether dietary supplementation with the α-glucosidase inhibitor miglitol from the preonset stage improves glycemic control and reduces the gene expression of inflammatory cytokines in peripheral leukocytes. The OLETF rats were fed a control diet or a diet containing 800 ppm miglitol (miglitol diet) for 40 weeks from 5 weeks of age (preonset stage). We determined nonfasting blood glucose, blood 1,5-anhydroglucitol, and messenger RNA levels of inflammatory cytokines in peripheral leukocytes in these rats. Nonfasting blood glucose concentrations gradually increased in OLETF rats fed the control diet, with significant increases at weeks 28 and 40 compared with week 0. In contrast, nonfasting blood glucose levels did not increase in miglitol-treated rats during the experimental period. Miglitol-treated rats had lower nonfasting blood glucose levels and higher 1,5-anhydroglucitol levels, a marker for glucose fluctuations, at week 40 than control rats. The gene expression of inflammatory cytokines including interleukin-6, tumor necrosis factor-α, and interferon-γ in peripheral leukocytes gradually increased during the development of diabetes in control rats, but not in miglitol-treated rats. Our results suggest that dietary supplementation with miglitol from the preonset stage in OLETF rats improves glycemic control and reduces gene expression of cytokines related to inflammation in peripheral leukocytes.

Yi-Qi-Zeng-Min-Tang, a Chinese medicine, ameliorates insulin resistance in type 2 diabetic rats.

To investigate the effects of the Chinese herbal decoction, Yi-Qi-Zeng-Min-Tang (YQZMT), on insulin resistance in type 2 diabetic rats. Sprague-Dawley rats were divided into two dietary regiments by feeding either normal pellet diet (NPD) or high fat diet (HFD). Four weeks later, the HFD-fed rats were injected intraperitoneally with low-dose streptozotocin (STZ). Rats with non-fasting blood glucose level ≥ 16.67 mmol/L were considered type 2 diabetic and further divided into five subgroups: the type 2 diabetes model group, low-dose, medium-dose and high-dose YQZMT groups, and rosiglitazone group. Age-matched NPD-fed rats served as controls. YQZMT or rosiglitazone were administered for 8 wk. Intraperitoneal glucose and insulin tolerance tests were performed before and after the treatment to measure the glucose tolerance and insulin sensitivity. Serum levels of biochemical parameters, adipocytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), as well as free fatty acids (FFAs), were also analyzed. There was significant elevation of insulin resistance and serum levels of fasting glucose (12.82 ± 1.08 mmol/L vs 3.60 ± 0.31 mmol/L, P < 0.01), insulin (7197.36 ± 253.89 pg/mL vs 4820.49 ± 326.89 pg/mL, P < 0.01), total cholesterol (TC) (8.40 ± 0.49 mmol/L vs 2.14 ± 0.06 mmol/L, P < 0.01), triglyceride (2.24 ± 0.12 mmol/L vs 0.78 ± 0.05 mmol/L, P < 0.01), low-density lipoprotein cholesterol (LDL-c) (7.84 ± 0.51 mmol/L vs 0.72 ± 0.04 mmol/L, P < 0.01) and decrease in high-density lipoprotein cholesterol (HDL-c) (0.57 ± 0.03 mmol/L vs 1.27 ± 0.03 mmol/L, P < 0.01) in the low-dose STZ and high-fat diet induced type 2 diabetic group when compared with the control group. Administration of YQZMT induced dose- and time-dependent changes in insulin resistance, glucose and lipid profile, and reduced levels of FFA, TNF-α and IL-6 in the type 2 diabetic rats. After the treatment, compared with the diabetic group, the insulin resistance was ameliorated in the high-dose YQZMT (2.82 g/100 g per day) group, with a significant reduction in serum glucose (12.16 ± 1.00 mmol/L vs 17.65 ± 2.22 mmol/L, P < 0.01), homeostasis model assessment of basal insulin resistance (22.68 ± 2.37 vs 38.79 ± 9.02, P < 0.05), triglyceride (0.87 ± 0.15 mmol/L vs 1.99 ± 0.26 mmol/L, P < 0.01), TC (3.31 ± 0.52 mmol/L vs 6.50 ± 1.04 mmol/L, P < 0.01) and LDL-c (2.47 ± 0.50 mmol/L vs 6.00 ± 1.07 mmol/L, P < 0.01), and a significant increase in HDL-c (0.84 ± 0.08 mmol/L vs 0.50 ± 0.03 mmol/L, P < 0.01). But the body weight was not changed significantly. YQZMT, which ameliorates insulin resistance and does not cause increase in body weight, may be a suitable therapeutic adjunct for the treatment of type 2 diabetes.

Diabetes and the risk of coronary heart disease in the general Japanese population: The Japan Public Health Center-based prospective (JPHC) study

ObjectiveAlthough diabetes has a great impact on coronary heart disease (CHD) in Western populations, there is limited evidence that diabetes influences CHD in the Japanese population. MethodsThe Japan Public Health Center-based prospective (JPHC) study conducted a follow-up of 31,192 individuals aged 40–69 years with no history of cardiovascular disease or cancer. Subjects were classified at baseline as normal, borderline diabetic or diabetic based on fasting and non-fasting blood glucose levels and the use of medication to treat diabetes. A Cox proportional hazards model was used to determine the association between diabetes and the risk of fatal and non-fatal CHD events after adjustment for potential confounders. ResultsDuring 12.9 years of follow-up (1990–2006), we identified 266 fatal and non-fatal coronary events using validated criteria. With normal individuals serving as a control, the hazard ratios for total incident CHD events after adjusting for sex, age, study community and fasting were 1.65 (95% CI, 1.19–2.29) and 3.05 (2.03–4.59) in the borderline and diabetic groups, respectively. These associations remained significant after adjustment for conventional risk factors. The population attributable fractions (PAF) of borderline diabetes and diabetes for CHD events were 6.9% and 6.3%, respectively. Furthermore, there was a trend for an association between an impaired fasting glucose (5.6–6.9mmol/l) and an increased risk of CHD events. ConclusionsThis prospective study suggests that diabetes and elevated glucose levels are associated with incident CHD in the general Japanese population. The PAF of diabetes for fatal and non-fatal coronary events was estimated to be moderate.

The Relationship of Glycemic Control to the Outcomes of Dental Extractions

The aim of this study was to determine whether glycemic control influences healing after tooth extractions. We enrolled 115 diabetic patients who required dental extractions in this prospective observer-blinded study. Epithelialization of extraction sites was assessed relative to the patient's history, non-fasting blood glucose levels, and glycosylated hemoglobin levels. Of 115 patients, 78 had 1- and 2-week follow-up data. There was no statistically significant difference in the rate of postextraction epithelialization between diabetic patients based on preoperative blood glucose levels, hemoglobin A1c levels, or patient history. Only the size of the extraction site at days 0 and 7 was predictive of future epithelialization. Glycemic control did not influence postextraction healing in diabetic patients. Recommendations for management of the diabetic patient requiring extractions are discussed.

Calcium Phosphate Cement Chamber as an Immunoisolative Device for Bioartificial Pancreas

This study examined a calcium phosphate cement (CPC) chamber as an immunoisolative device to facilitate the use of xenogeneic cell sources without immunosuppression for the bioartificial pancreas (BAP). Mouse insulinoma cells were encapsulated in agarose gel and then enclosed in a CPC chamber to create a BAP. Bioartificial pancreas were evaluated by cell viability, live-dead cell ratio, and cytokine-mediated cytotoxicity assay and implanted into the peritoneal cavity of diabetic rats. Nonfasting blood glucose and serum insulin levels were analyzed perioperatively; BAPs were also retrieved for histological examination. Insulinoma cells enclosed in the CPC chamber had normal viability, cell survival, and insulin secretion that was even cultured in media with cytokines. The nonfasting blood glucose level of rats was decreased from 460 +/- 50 to 132 +/- 43 mg/dL and maintained euglycemia for 22 days; serum insulin level was increased from 0.34 +/- 0.11 to 1.43 +/- 0.30 microg/dL after operation. Histological examination revealed the fibrous tissue envelopment, and immune-related cells that competed for oxygen resulting in hypoxia could be attributed to the dysfunction of BAPs. This study proved the feasibility for using a CPC chamber as an immunoisolative device for the BAP. An alternative implanted site should be considered to extend the functional longevity of BAPs in further study.

The cytoprotection of chitosan based hydrogels in xenogeneic islet transplantation: An in vivo study in streptozotocin-induced diabetic mouse

Immune rejection and scarcity of donor tissues are the restrictions of islets transplantation. In this study, the cytoprotection of chitosan hydrogels in xenogeneic islet transplantation was demonstrated. Wistar rat islets encapsulated in chitosan hydrogels were performed glucose challenge test and live/dead cell staining in vitro. Islets/chitosan hydrogels were transplanted into the renal subcapsular space of diabetic C57BL/6 mice. Non-fasting blood glucose level (NFBG), body weight, intraperitoneal glucose tolerance test (IPGTT), and glucose disappearance rate were determined perioperatively. The serum insulin level was analyzed, and the kidney transplanted with islets/chitosan hydrogels were retrieved for histological examination after sacrifice. The present results showed that islets encapsulated in chitosan hydrogels secreted insulin in response to the glucose stimulation as naked islets with higher cell survival. The NFBG of diabetic mice transplanted with islets/chitosan hydrogels decreased from 487 ± 46 to 148 ± 32 at one day postoperation and maintained in the range of 201 ± 36 mg/dl for four weeks with an increase in body weight. IPGTT showed the glucose disappearance rate of mice transplanted with islets/chitosan hydrogels was significant faster than that of mice transplanted with naked islets; the serum insulin level increased from 0.29 ± 0.06 to 1.69 ± 0.65 μg/dl postoperatively. Histological examination revealed that the islets successfully engrafted at renal subcapsular space with positive insulin staining. The immunostain was negative for neither the T-cell lineages nor the monocyte/macrophages. This study indicates that the chitosan hydrogels deliver and protect encapsulated islets successfully in xenotransplantation.

The in vivo performance of polyvinyl alcohol macro-encapsulated islets

Islet transplantation is a method for the treatment of type 1 diabetes mellitus (DM) and has been widely performed around the world. The long-term cryopreservation of islets shows many advantages in the field of islet transplantation. Previous studies have described the development of sheet-type polyvinyl alcohol (PVA) macro-encapsulated islets (MEI) to treat type 1 DM without any immunotherapy. The present study examined their beneficial effects on islet cryopreservation. PVA MEI of Wistar rats were divided into three groups of 1-day, 7-day and 30-day cryopreservation at −80 °C. The 30-day group showed a lower recovery rate of the islet number and impaired insulin release in comparison to the 1-day group, whereas no significant differences of the in vitro results were observed between the 1-day and 7-day groups. The MEI transplantation recipient mice in the 1-day and 7-day groups reached normoglycemia for a 4-week observation period, and the recipients in 30-day group also showed a significant decrease followed by a slightly higher non-fasting blood glucose level. These results suggest that the PVA MEI are useful for islet long-term cryopreservation, and that the use of cryopreserved PVA MEI may, therefore, be a promising modality for performing DM therapy.

Longitudinal impact of physical activity on lipid profiles in middle-aged adults: the Atherosclerosis Risk in Communities Study

Evidence exists that increased levels of physical activity decrease the population burden of cardiovascular disease (CVD). Although risk factors for CVD, including plasma lipids and lipoproteins, have been associated with physical activity, studies including a sizeable number of minority participants are lacking. Our purpose was to interrogate the longitudinal effect of physical activity on plasma lipids and lipoproteins in the African American and white participants of the Atherosclerosis Risk in Communities (ARIC) Study. Nine years of follow-up data on 8,764 individuals aged 45-64 years at baseline were used in linear mixed-effects models to estimate the association between increases in baseline physical activity on mean change in HDL, LDL, total cholesterol, and triglyceride levels. Increases in the level of activity were associated with increases in HDL in all strata and decreases in triglycerides among white participants. Physical activity was associated with LDL in all women, while the association with total cholesterol was limited to African American women. This study is one of the few to investigate the effect of physical activity on lipids and lipoproteins in a race- and sex-specific manner. Overall our results highlight the importance of physical activity on plasma lipid profiles and provide evidence for novel differential associations.