Reduced Blood Glucose Concentrations Research Articles

The influence of exendin and GLP-1 on VCAM-1 and ICAM-1 production in endothelium stimulated by TNF-α and glycated albumin

A growing body of evidence indicates that incretins may have pleiotropic beneficial effects beyond lowering glucose blood concentration. The effect of GLP-1 and exendin-4 on coronary arteries endothelium in diabetic and obese individuals has been studied widely. TNF-a is one of adipocytokines. The aim of our study was to evaluate the influence of glycated albumin (GlyAlb; 100; 500 and 1000 mg/L) and proinflammatory cytokine, TNF-α (2.5 and 10 ng/mL), on expression of ICAM-1 and VCAM-1 in cultured human endothelial cells derived from coronary arteries. The next goal of the study was to evaluate the influence of GLP-1 (10 nM and 100 nM) and its analogue, exendin-4 (1 nM and 10 nM), on the expression of ICAM-1 and VCAM-1 in these cell line. TNF-a statistically significantly increased VCAM-1 production by endothelial cells, whereas GlyAlb statistically significantly augmented the expression of both tested adhesion mole- cules. Exendin-4 and GLP-1 statistically significantly reduced the expression of VCAM-1 in endothelial cells stimulated by GlyAlb in dose-de- pendent manner. When TNF-a was used as the stimulant only exendin-4 in the concentration of 10 nM statistically significantly reduced the expression of VCAM-1. Studied incretins in their both concentrations statistically significantly reduced the expression of ICAM-1 in endothelial cells stimulated by GlyAlb. The influence of TNF- a on the expression of ICAM-1 was statistically significantly reduced by both concentrations of exendin-4 but only by the higher concentration of GLP-1. The results of our present study indicate that incretins may present a group of agents developing pleiotropic effects beyond the reduction of blood glucose concentration. Their vaso-protective and cardioprotective action may be of importance in diabetic and obese individuals.

Evaluation of an oral insulin formulation in normal and diabetic rats

Aim:As injection is not an ideal means for insulin delivery, various attempts have been made to administer insulin orally until now. The development of an oral dosage form of insulin would help diabetic patients and make the treatment more convenient. The aim of the present study is to evaluate the effectiveness of an oral insulin formulation containing polar and non-polar ingredients.Materials and Methods:New excipient for oral insulin administration in normal and diabetic rats was evaluated by measuring blood glucose concentrations in two groups (10 rats each) of normal and streptozotocin-induced diabetic rats. Oral insulin was administrated and blood glucose was measured by glucometer at 0, 1, 2, 3 and 4 h post-feeding. The data was compared by Student's t test.Results:Oral insulin formulation significantly (P<0.05) reduced blood glucose from 100 mg/dl to 33.73 mg/dl and 451.66 mg/dl to 200.83 mg/dl at 4 h in normal and diabetic rats, respectively.Conclusion:The novel excipient used could protect insulin from gastric and pancreatic enzymes and reduce blood glucose concentration in both healthy and diabetic rats suggesting that oral delivery of insulin is feasible in a near future.

Hepatic Suppression of Foxo1 and Foxo3 Causes Hypoglycemia and Hyperlipidemia in Mice

Dysregulation of blood glucose and triglycerides are the major characteristics of type 2 diabetes mellitus. We sought to identify the mechanisms regulating blood glucose and lipid homeostasis. Cell-based studies established that the Foxo forkhead transcription factors Forkhead box O (Foxo)-1, Foxo3, and Foxo4 are inactivated by insulin via a phosphatidylinositol 3-kinase/Akt-dependent pathway, but the role of Foxo transcription factors in the liver in regulating nutrient metabolism is incompletely understood. In this study, we used the Cre/LoxP genetic approach to delete the Foxo1, Foxo3, and Foxo4 genes individually or a combination of two or all in the liver of lean or db/db mice and assessed the role of Foxo inactivation in regulating glucose and lipid homeostasis in vivo. In the lean mice or db/db mice, hepatic deletion of Foxo1, rather than Foxo3 or Foxo4, caused a modest reduction in blood glucose concentrations and barely affected lipid homeostasis. Combined deletion of Foxo1 and Foxo3 decreased blood glucose levels, elevated serum triglyceride and cholesterol concentrations, and increased hepatic lipid secretion and caused hepatosteatosis. Analysis of the liver transcripts established a prominent role of Foxo1 in regulating gene expression of gluconeogenic enzymes and Foxo3 in the expression of lipogenic enzymes. Our findings indicate that Foxo1 and Foxo3 inactivation serves as a potential mechanism by which insulin reduces hepatic glucose production and increases hepatic lipid synthesis and secretion in healthy and diabetic states.

Potential application of Russian Tarragon (Artemisia dracunculus L.) in health and sports

Tarragon is a spice herb with a long history of culinary and medical use. There exist two cultivars of this species: French Tarragon is used as a spice in cuisine and Russian Tarragon (RT) has been used medically in Russia and middle Asia, mainly to treat gastrointestinal disorders. However, recent studies also reported possible antidiabetic and hypoglycemic activities. Ribnickyet al. demonstrated that an ethanolic extract of RT was able to reduce blood glucose concentration in rodents. Tarragon like many other spices contains potential harmful essential oil constituents like estragole and methyleugenol. Thus, it was officially advised to limit the intake of such herbal spices. Therefore, as a solution to this problem, an aqueous extract of RT (RTE), which does not contain these compounds, was developed (Finzelberg GmbH & Co.KG, Germany) for further investigation. In vivo animal and human study demonstrate promising potential of the aqueous extract as a new potent antidiabetic agent. Methods For the in vivo studies a standard animal model for testing of antidiabetic activity was used (non-fasted Wistar rats, n=8 / group). Blood glucose and insulin levels were determined with glucose challenge (2g/kg glucose infusion) and without (basal). A randomized, double-blind, cross-over clinical trial in 12 non-diabetic men was performed to approve the effect of RT on serum glucose and insulin levels, as well as cardiovascular parameters. Subjects reported to the lab on 2 different mornings separated by 1 to 2 weeks, and ingested 75 g of dextrose in solution. 15 min before ingestion, men ingested e ither 2go f RT or placebo. Blood samples were collected before ingestion of the RT and placebo, and several time points after dextrose administration. Results It was shown that the aqueous extract of RT lowered the blood glucose level in both animals and humans (albeit non-statistically). The area under the blood glucose curve (AUC) was significantly decreased after oral administration of aqueous RTE to non-fasted Wistar rats (19,000 rel. AUC vs. 30,000 rel. AUC, n=8, p<0.001). For serum glucose, no condition (p=0.19) or condition x time (p=0.99) effect was noted in the clinical trial. Similar findings were noted for insulin. However, a time effect was noted (p<0.0001), with values at the 15 and 30 min blood collection times higher than preingestion. Additionally, a potential positive impact of RTE administration on certain cardiovascular parameters was noted. Conclusion

Influence of Exercise on Skill Proficiency in Soccer

The ability to maintain technical performances (i.e. skills) throughout soccer match-play is considered to be crucial in determining the outcome of competitive fixtures. Consequently, coaches dedicate a large proportion of time to practicing isolated skills, such as passing, shooting and dribbling. Unlike other elements that contribute to team-sport performances, it is unusual for coaches to use methods other than observations to assess changes resulting from technical training. Researchers have employed various tests to measure isolated soccer skills; however, reliance on outcome measures that include number of contacts (ball juggling tasks), time (dribbling tasks) and points scored (criterion-based passing and shooting tests) means that the outcomes are difficult for coaches to interpret. Skill tests that use video-analysis techniques to measure ball speed, precision and success of soccer skills offer valid and reliable alternatives. Although equivocal results are published, skill performances can be affected by assorted factors that threaten homeostasis, including match-related fatigue, dehydration and reductions in blood glucose concentrations. While acknowledging methodological constraints associated with using skill tests with limited ecological validity and cognitive demands, the effects of these homeostatic disturbances might vary according to the type of skill being performed. Shooting performances appear most susceptible to deterioration after exercise. Strategies such as aerobic training, fluid-electrolyte provision and acute carbohydrate supplementation have been found to improve proficiency in technical actions performed after soccer-specific exercise. However, mechanisms that cause deterioration in skill during soccer-specific exercise remain to be fully elucidated and strategies to optimize technical performance throughout match-play are warranted.

Effects of biotin deficiency on pancreatic islet morphology, insulin sensitivity and glucose homeostasis

Several studies have revealed that physiological concentrations of biotin are required for the normal expression of critical carbohydrate metabolism genes and for glucose homeostasis. However, the different experimental models used in these studies make it difficult to integrate the effects of biotin deficiency on glucose metabolism. To further investigate the effects of biotin deficiency on glucose metabolism, we presently analyzed the effect of biotin deprivation on glucose homeostasis and on pancreatic islet morphology. Three-week-old male BALB/cAnN Hsd mice were fed a biotin-deficient or a biotin-control diet (0 or 7.2 μmol of free biotin/kg diet, respectively) over a period of 8 weeks. We found that biotin deprivation caused reduced concentrations of blood glucose and serum insulin concentrations, but increased plasma glucagon levels. Biotin-deficient mice also presented impaired glucose and insulin tolerance tests, indicating defects in insulin sensitivity. Altered insulin signaling was linked to a decrease in phosphorylated Akt/PKB but induced no change in insulin receptor abundance. Islet morphology studies revealed disruption of islet architecture due to biotin deficiency, and an increase in the number of α-cells in the islet core. Morphometric analyses found increased islet size, number of islets and glucagon-positive area, but a decreased insulin-positive area, in the biotin-deficient group. Glucagon secretion and gene expression increased in islets isolated from biotin-deficient mice. Our results suggest that biotin deficiency promotes hyperglycemic mechanisms such as increased glucagon concentration and decreased insulin secretion and sensitivity to compensate for reduced blood glucose concentrations. Variations in glucose homeostasis may participate in the changes observed in pancreatic islets.

A Review of Dietary Fiber and Health: Focus on Raisins

Fibers vary in their physiologic effects. For example, viscous fibers may delay gastric emptying of ingested foods into the small intestine, creating a sensation of fullness; reduce blood glucose concentrations; and potentially benefit insulin sensitivity. They also improve blood cholesterol levels. Insoluble fibers are poorly absorbed and are known to improve fecal bulk and laxation and ameliorate constipation. Despite these numerous benefits, most Americans do not get enough of either kind of fiber in the diet. Some have argued that fiber-rich foods are not appetizing and therefore avoided. Raisins contain both forms of fiber and have a sweet flavor. This review provides support for consuming adequate fiber in the diet and suggests a role for raisins to help increase total dietary fiber.

Higher plasma pyridoxal 5′-phosphate is associated with better blood glucose responses in critically ill surgical patients with inadequate vitamin B-6 status

Stress, inflammation, and clinical conditions may increase the utilization and metabolic turnover of vitamin B-6 and lower the body pool of vitamin B-6. There is the possibility that hyperglycemia in critically ill patients might be at least partially due to compromised vitamin B-6 status. The purpose of this study was to compare blood glucose responses between critically ill surgical patients with adequate and deficient vitamin B-6 status. The study was designed as a cross-sectional observational study. Thirty-four patients in the surgical intensive care unit (SICU) were enrolled. The severity of illness (APACHE II score), the length of ventilation dependency, and the lengths of SICU and hospital stay were recorded. The levels of serum hemoglobin, hematocrit, albumin, prealbumin, C-reactive protein, glucose, insulin, glycated hemoglobin, C-peptide and creatinine were determined. Vitamin B-6 intake was recorded for 7 days. Vitamin B-6 status was assessed by direct measures [plasma and erythrocyte pyridoxal 5'-phosphate (PLP), pyridoxal (PL) and 4-pyridoxic acid (4-PA), and urinary 4-PA] and indirect measures [erythrocyte alanine and aspartate aminotransaminase activity coefficient]. Fourteen patients were classified into the deficient vitamin B-6 group (plasma PLP<20nmol/L), while there were 20 patients in the adequate vitamin B-6 group. The mean serum glucose concentration of both groups indicated patients was in the hyperglycemic state (serum glucose>126mg/dL). However, mean serum glucose concentration significantly decreased by day 7 in the adequate vitamin B-6 group, whereas patients still remained in the hyperglycemic state (serum glucose>126mg/dL) in the deficient vitamin B-6 group. There were significantly correlations of relatively higher plasma PLP at admission (day 1) with the reduction of blood glucose concentration (r(s)=0.72, p=0.029) on day 7 in the deficient vitamin B-6 group. However, erythrocyte PLP concentration was positively associated with blood glucose level (r(s)=0.88, p=0.002) at admission in the deficient vitamin B-6 group after adjusting for age, gender, APACHE II score, diabetic history and insulin therapy. Surgically ill patients with adequate plasma PLP concentration at admission showed improved blood glucose response at day 7. Higher plasma PLP at admission was a major contributing factor in the reduction of glucose concentration in critically ill surgical patients with deficient vitamin B-6 status.

Perioperative use of metformin in cardiac surgery

Metformin is an oral antidiabetic agent, used to reduce blood glucose concentration in patients with non-insulin-dependent diabetes mellitus. Metformin was approved in Europe in 1957, and it is used for the treatment of non-insulin-dependent diabetes mellitus for more than 50 years. One of the most serious complications of the treatment with this drug is metformin-induced lactic acidosis. It is a rare but dangerous metabolic complication with a mortality rate of up to 50% that can result from the accumulation of lactates. Lactic acidosis is also associated with conditions such as diabetes mellitus, significant tissue hypoperfusion, and hypoxemia caused by lactic acid overproduction or underutilization. It is characterized by an increased serum lactate level (>5mmol/L or >45 mg/dL), decreased blood pH (<7.35), and electrolyte imbalance with an increased anion gap. The rate of lactic acidosis in patients receiving metformin is not precisely known. The estimated incidence of this syndrome is 2-9 cases per 100 000 patients. However, in the majority of cases, lactic acidosis is diagnosed in patients with severe acute renal failure, which itself can cause lactic acidosis. Currently, there are no standardized guidelines for metformin administration during the perioperative period, and published data remain controversial. According to some investigators, metformin should be withdrawn before major surgery. Concerns have been raised for the use of metformin in patients with cardiovascular, renal, hepatic, and respiratory failure. The aim of the article is to overview the frequency of metformin-caused lactic acidosis and the latest recommendations for the use of metformin in the perioperative period proposed in recent years.

The function of porcine PPARγ and dietary fish oil effect on the expression of lipid and glucose metabolism related genes

Peroxisome-proliferator-activated receptor γ (PPARγ) plays a critical role in regulation of adipocyte differentiation and insulin sensitivity. To become functional, PPARγ must be activated by binding an appropriate ligand. Polyunsaturated fatty acids (PUFA) are potential ligands for PPARγ. The current experiment was designed to determine the potential for PUFA, particularly eicosapentaenoic acid and docosahexaenoic acid, to activate the function of porcine PPARγ in vivo. Transgenic mice, expressing porcine PPARγ in skeletal muscle were generated and fed with a high-saturated fat (beef tallow) or high-unsaturated fat (fish oil) diet for 4 months. When transgenic mice were fed a fish oil supplemented diet, the expression of adipogenic and glucose uptake genes was increased, leading to reduced plasma glucose concentration. The PPARγ transgene increased the expression of Glut4 in the muscle. This result suggests that there was increased glucose utilization and, therefore, a reduced blood glucose concentration in the transgenic mice. Also, the plasma adiponectin was elevated by fish oil treatment, suggesting a role of adiponectin in mediating the PUFA effect. These results suggest that PUFA may serve as a natural regulator of glucose uptake in vivo and these effects are mainly through PPARγ function.

Modeling the effects of hypoglycemia on a two-choice task in adult humans.

Previous research has demonstrated that hypoglycemia causes reaction times to be slower and more variable. Reaction time tests, however, use multiple cognitive and noncognitive processes. This study is the first to use a validated sequential sampling model (diffusion model) applied to results obtained from a simple 2-choice task in adult humans to assess the effects of hypoglycemia on the basic parameters of decision making. Fourteen adult volunteers were tested on a numerosity discrimination task with and without reduced blood glucose concentrations. The results were analyzed with a model that dissects the components of processing that underlie decisions: the quality of the information on which a decision is based (drift rate), the critical amount of evidence that must be accumulated before a decision is made (boundary separation), and the time taken by nondecision processes. Hypoglycemia resulted in a reduction of mean drift rate from 0.290 to 0.211, t(13) = 4.10, p < .05. No effect of experimental state was observed on the amount of evidence required to make a decision or peripheral and motor processes. This study locates the precise processing deficit associated with hypoglycemia and provides further understanding of the precise cognitive effect of hypoglycemia. Further research into the amelioration of these effects is required.

Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet-induced obese rats

BackgroundThe metabolic syndrome, known also as the insulin resistance syndrome, refers to the clustering of several risk factors for atherosclerotic cardiovascular disease. Dyslipidaemia is a hallmark of the syndrome and is associated with a whole body reduction in the activity of lipoprotein lipase (LPL), an enzyme under the regulation of the class of nuclear receptors known as peroxisome proliferator-activated receptor (PPAR). Glycyrrhizic acid (GA), a triterpenoid saponin, is the primary bioactive constituent of the roots of the shrub Glycyrrhiza glabra. Studies have indicated that triterpenoids could act as PPAR agonists and GA is therefore postulated to restore LPL expression in the insulin resistant state.ResultsOral administration of 100 mg/kg of GA to high-fat diet-induced obese rats for 28 days led to significant reduction in blood glucose concentration and improvement in insulin sensitivity as indicated by the homeostasis model assessment of insulin resistance (HOMA-IR) (p < 0.05). LPL expression was up-regulated in the kidney, heart, quadriceps femoris, abdominal muscle and the visceral and subcutaneous adipose tissues but down-regulated in the liver - a condition in reverse to that seen in high-fat diet-induced obese rats without GA. With regard to lipid metabolism, GA administration led to significant hypotriglyceridemic and HDL-raising effects (p < 0.05), with a consistent reduction in serum free fatty acid, total cholesterol and LDL cholesterol and significant decrease in tissue lipid deposition across all studied tissue (p < 0.01).ConclusionIn conclusion, GA may be a potential compound in improving dyslipidaemia by selectively inducing LPL expression in non-hepatic tissues. Such up-regulation was accompanied by a GA-mediated improvement in insulin sensitivity, which may be associated with a decrease in tissue lipid deposition. The HDL-raising effect of GA suggests the antiatherosclerotic properties of GA.

Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial

Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes. ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA(1c) concentrations (>7.5%), and cardiovascular disease (or >or=2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A(1c) [HbA(1c)] of <6.0%) or standard (7.0-7.9%) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291.7 micromol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620. 10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1.00, 95% CI 0.88-1.14; p=1.00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0.96, 0.89-1.02; p=0.19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 [HR 0.95, 95% CI 0.85-1.07, p=0.42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0.95, 0.89-1.01, p=0.12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Seven secondary measures at study end favoured intensive therapy (p<0.05). Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia. US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.

▼Liraglutide for type 2 diabetes?

Several drugs that act on the incretin hormonal system are now licensed in the UK as add-on therapy for patients with type 2 diabetes mellitus and inadequate glycaemic control.1 ▼Liraglutide...

New drugs: Liraglutide, dalfampridine, and abobotulinumtoxinA

Antidiabetic agent Liraglutide (Victoza—Novo Nordisk) is an analog of glucagon-like peptide-1 (GLP-1) and acts as a GLP-1 receptor agonist. Its properties are most similar to those of exenatide (Byetta), and both agents are administered subcutaneously. Liraglutide and exenatide reduce blood glucose concentrations via several mechanisms that include increased insulin release in the presence of elevated glucose concentrations, decreased glucagon secretion, and delayed gastric emptying. Liraglutide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes and may be used as monotherapy or in conjunction with one or more oral antidiabetic drugs, such as metformin, glimepiride, or a thiazolidinedione. However, it is not recommended as first-line therapy for patients inadequately controlled on diet and exercise, whereas the labeling for exenatide does not include this limitation. The effectiveness of liraglutide was demonstrated in studies in which it was used alone or in patients also treated with metformin and/or glimepiride or with metformin and rosiglitazone (Avandia). In the study in which liraglutide monotherapy was compared with glimepiride monotherapy, the new drug provided significantly greater reductions in glycosylated hemoglobin (A1C; –0.8% and –1.1% with daily doses of 1.2 and 1.8 mg liraglutide, respectively, compared with –0.5% with 8 mg daily glimepiride, after 52 weeks). In one study, either liraglutide (1.8 mg once a day) or exenatide (10 μg twice a day) was added to a regimen of metformin and/or glimepiride. After 26 weeks, patients receiving liraglutide achieved a significantly greater reduction in A1C from baseline (–1.2%) compared with 0.79% in patients receiving exenatide. Liraglutide also provided significantly greater reductions in fasting plasma glucose, but patients treated with exenatide experienced a greater reduction in postprandial glucose after breakfast and dinner. As with exenatide, many patients treated with liraglutide lose weight (~3 kg on average); this is an added benefit for these medications, which are often used in patients who are overweight. In contrast, use of glimepiride and other sulfonylureas is often associated with weight gain. The adverse events reported most often in the study in which liraglutide was used as monotherapy included nausea (28%), diarrhea (17%), vomiting (11%), constipation (10%), upper respiratory tract infection (10%), and headache (9%). As with exenatide, pancreatitis has been reported infrequently. Caution should be exercised in patients with a history of pancreatitis, particularly when treatment is initiated and following increases in dosage. If symptoms suspected to be associated with pancreatitis develop, treatment should be discontinued. If pancreatitis is confirmed, liraglutide should not be resumed. Liraglutide has been reported to cause malignant thyroid C-cell tumors in rodents, and this is the subject of a boxed warning in the labeling for the drug. Although whether liraglutide causes such tumors, including medullary thyroid carcinoma (MTC), in humans is unknown, the new drug is contraindicated in patients with a personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2. The labeling for exenatide does not address this problem, although recent observations suggested the possibility of an increased cancer risk with its use. Many of the patients in the clinical studies were tested for the presence of anti-liraglutide antibodies at the end of treatment. These antibodies were detected in approximately 9% of those tested, but the potential for significant neutralization of the clinical benefit was not assessed. Although experienced infrequently, immunogenicity-related events, including urticaria, were reported more often in patients treated with liraglutide (0.8%) than with other antidiabetic agents. Liraglutide is classified in Pregnancy Category C and should only be used during pregnancy if the anticipated benefit justifies the risk to the fetus. Whether the drug is excreted in human milk is not known, and a decision should be made whether to discontinue nursing or not use the drug. The effectiveness and safety of liraglutide in pediatric patients have not been established. Liraglutide is not likely to cause hypoglycemia. However, serious hypoglycemia may result when it is used concurrently with an insulin secretagogue such as a sulfonylurea. The risk of hypoglycemia may be reduced by decreasing the dosage of the latter agent when treatment with liraglutide is initiated. Because liraglutide delays gastric emptying, a potential exists for altered absorption of oral medications used concurrently. Although interactions of this type were not reported in the clinical studies, the potential for changes in absorption and activity of orally administered drugs should be monitored. Liraglutide is administered subcutaneously in the abdomen, thigh, or upper arm. Following administration, maximum concentrations are attained within 12 hours, and the absolute bioavailabil-

In vivo gene delivery by cationic tetraamino fullerene

Application of nanotechnology to medical biology has brought remarkable success. Water-soluble fullerenes are molecules with great potential for biological use because they can endow unique characteristics of amphipathic property and form a self-assembled structure by chemical modification. Effective gene delivery in vitro with tetra(piperazino)fullerene epoxide (TPFE) and its superiority to Lipofectin have been described in a previous report. For this study, we evaluated the efficacy of in vivo gene delivery by TPFE. Delivery of enhanced green fluorescent protein gene (EGFP) by TPFE on pregnant female ICR mice showed distinct organ selectivity compared with Lipofectin; moreover, higher gene expression by TPFE was found in liver and spleen, but not in the lung. No acute toxicity of TPFE was found for the liver and kidney, although Lipofectin significantly increased liver enzymes and blood urea nitrogen. In fetal tissues, neither TPFE nor Lipofectin induced EGFP gene expression. Delivery of insulin 2 gene to female C57/BL6 mice increased plasma insulin levels and reduced blood glucose concentrations, indicating the potential of TPFE-based gene delivery for clinical application. In conclusion, this study demonstrated effective gene delivery in vivo for the first time using a water-soluble fullerene.

Antioxidant effect of zinc, selenium and their combination on the liver and kidney of alloxan-induced diabetes in rats

Zinc and selenium have been shown to singly act in normalising glycaemia and are also postulated to possess insulin-like functions. Supplementation with their combination in the diets of rats with alloxan-induced diabetes was investigated with the aim of investigating their effects on glucose homeostasis and their antioxidant properties on the liver and kidney of alloxan-induced diabetic rats. Thirty-five rats were randomly assigned to five groups and four groups were made diabetic by the administration of 150 mg/kg body weight of alloxan monohydrate, after which three diabetic groups were fed with diets supplemented with zinc, selenium and a combination of the two. Zinc, selenium and the combination significantly reduced blood glucose concentration, restored hepatic functions, increased the antioxidant status of the diabetic rats and reduced lipid peroxidation in both the hepatic and renal tissues. It was concluded that supplementation with zinc, selenium and the combination facilitated glucose uptake, prevented oxidative stress, reduced lipid peroxidation and preserved hepatic function in diabetes.

An overview of salsalate as a potential antidiabetic therapy

The incidence of type 2 diabetes is increasing at an alarming rate throughout the world. This is in large part due to the increase in obesity and the aging of the population. Therefore, new medications to combat type 2 diabetes are needed. Salicylates have been used as analgesics and antiinflammatory agents for several decades. Incidentally, in some studies it was noted that high-dose salicylate treatment reduced blood glucose concentrations. Recently, inflammation has been strongly associated with insulin resistance and diabetes. Some studies show that salsalate, which is a nonacetylated form of salicylate, reduces blood glucose concentrations in patients with type 2 diabetes, as well as in insulin-resistant patients without diabetes. Postulated mechanisms include the inhibition of nuclear factor NF-kappa-B. Discussed in this review are the efficacy, safety and mechanisms of salsalate relevant to the treatment of type 2 diabetes.

Effect of leaf extract of &lt;i&gt;Pseudocedrela kotchyi&lt;/i&gt;on blood glucose concentration of alloxan induced diabetic albino wister rats

The effect of leaf extract of Pseudocedrela kotchi (PK) on blood glucose of alloxan induced albino wistar rats was evaluated. Experimental animals received daily oral administration of extract of Pseudocedreala kotchi for 14 days. The effect of 200 mg/kg dose was studied during the treatment period. There was a significant reduction in blood glucose concentration (p being 5.5 ± 0.33 mmol/L for normal control, 7.0 ± 0.40 mmol/L for diabetic control group and 4.8 ± 0.24 mmol/L for diabetic treated group. The findings of this study suggest that extract of Pseudocedreala kotchi has hypoglycemic effect.

Additive postprandial blood glucose–attenuating and satiety-enhancing effect of cinnamon and acetic acid

Cinnamon and vinegar or acetic acid were reported to reduce the postprandial blood glucose response. We hypothesized that the combination of these substances might result in an additive effect. Therefore, we determined the 2-hour postprandial blood glucose and satiety response to a milk rice meal supplemented with either cinnamon or acetic acid on their own or in combination. Subjects (n = 27) consumed the meal on 4 occasions as either pure (control trial), with 4 g cinnamon, 28 mmol acetic acid, or the combination of cinnamon + acetic acid. Blood glucose and satiety were assessed before eating and 15, 30, 45, 60, 90, and 120 minutes postprandially. At 15 minutes, the combination of cinnamon + acetic acid resulted in a significantly reduced blood glucose concentration compared with the control meal (P = .021). The incremental area under the blood glucose response curve over 120 minutes did, however, not differ between the trials (P = .539). The satiety score of the cinnamon + acetic acid trial was significantly higher than that in the control trial at 15 (P = .024) and 30 minutes (P = .024), but the incremental area under the curve of the satiety response did not differ (P = .116) between the trials. In conclusion, the significant effect of the combination of cinnamon and acetic acid on blood glucose and satiety immediately after meal intake indicated an additive effect of the 2 substances. Whether larger doses of cinnamon and acetic acid may result in a more substantial additive effect on blood glucose or satiety remains to be investigated.