Insulin Levels In Rats Research Articles

The Effects Of Simvastatin On Islets Of Langerhans In The Pancreas Of Rats: A Histological And Biochemical Study

Objective: This study explored the effect of simvastatin on the histomorphology of islets of Langerhans, glucose and insulin levels in rats. Study Design: The study was a one-year laboratory-based experimental control trial. Place and duration of study: It was conducted at Army Medical College Rawalpindi, in collaboration with the National Institute of Health Islamabad and Armed Force Institute of Pathology Rawalpindi. Methods: A one-year, laboratory-based, two-group experimental control trial was conducted. Thirty rats were assigned to each group: a control group receiving saline injections, and a simvastatin group receiving a simvastatin 60 mg/kg/day. Histological analysis of pancreatic islets, and measurements of blood glucose and insulin levels were performed. Statistical analysis was conducted using independent sample t-tests, with significance set at p < 0.005. Results: While simvastatin treatment did not affect the number of islets of Langerhans, The area of pancreatic islets of Langerhans was significantly higher in the simvastatin treatment group compared to control (52,664±38,871 μm2 vs 24,643±16,256 μm2, p=0.001). Serum insulin levels were also significantly elevated with simvastatin treatment (21.49±7.03 μIU/ml) compared to control (16.72±5.38 μIU/ml) (p=0.005). There were no significant differences in weekly fasting blood glucose levels at 4 or 12 weeks between groups (p>0.05). These findings suggest potential modulation of pancreatic islet function by simvastatin without affecting glycemic control in this model. Conclusions: These findings demonstrate that simvastatin treatment significantly impacts the morphology and function of pancreatic islets in rats, increasing insulin secretion without affecting blood glucose levels. Further research is necessary to elucidate the underlying mechanisms and clinical implications of these observations. Keywords: Simvastatin, islets of Langerhans, Sprague-Dawley rats, insulin, glucose, pancreas.

Crude extract from Euphorbia prostrata extendedcurative period of glibenclemide inalloxan-induced diabetic rats.

Euphorbia prostrata is traditionally used alongside antidiabetic agents to manage diabetes. Bioactive ingredients of medicinal herbs may alter the overall pharmacokinetics of antidiabetic agents. We assessed hypoglycemic activities of ethanolic plant extract (EPE) singly and its effects on antidiabetic properties of gliclazide, glibenclemide and metformin in allaxonized rats. Varying concentrations of EPE (250 and 500mg/kg) with or without metformin (10mg/kg), glibenclemide (2mg/kg) and gliclazide (5mg/kg) were orally administered to evaluate herb-drug interaction. The levels of blood glucose declined significantly after treatment with metformin, glibenclemide and gliclazide singly (p<0.01) or concomitantly with EPE (p<0.001). Concentration dependent mild to moderate reduction (5.2and 10.0%) was registered in blood glucose for 250 and500mg/kg of EPE respectively. The overall reduction in blood glucose due to combined treatment with EPE and standard agents was additive. On the other hand, synergistic herb-drug interaction was registered for insulin levels in rats that received glibenclamide and gliclazide alongside EPE. Extract with metformin had antagonistic insulin outcome. Regarding the duration of hypoglycemic activities, periodical changes were similar in case of glibenclamide and gliclazide separately or in combination with EPE. However, in case of metformin with extract, the blood glucose continued to decline for 14h and retained at 15.0% below the baseline values even after 24h of treatment. In conclusion, the extract itself had weak hypoglycemic effects but prolonged the therapeutic duration of metformin to more than 24h when administered combinedly.

AKTIVITAS ANTIHIPERGLIKEMIA FRAKSI ETIL ASETAT DAUN SALAM (Syzygium polyanthum) TERHADAP TIKUS PUTIH YANG DIINDUKSI ALOKSAN MONOHIDRAT

Bay leaf (Syzygium polyanthum) is traditionally used for diabetes treatment in Indonesia. It’s contains antioxidant that prevent the free radicals due to hyperglycemic condition. The purpose of this study is to demonstrate the ability of the ethyl acetate fraction of bay leaf in male white rats had hyperglycemia due to alloxan administration. This study used laboratory tests in which up to 24 white rats were randomly separated into six groups. Intraperitoneal administration of alloxan at a dose of 170 mg/Kgbw is used to induce hyperglycemia. A group of healthy rats (K-) were administered 0,5% CMC Na suspension 1mL/day. A group of hyperglycemic rats (K+) received metformin at a dose of 45 mg/Kgbw/1mL/day, while a group of hyperglycemic rats (P0) received 0.5% CMC Na suspension at a dose of 1mL/day. Three hyperglycemia treatment groups received different amounts of ethyl acetate fraction of bay leaf for 14 days. The P1 group received 125 mg/Kgbw/1mL/day of bay leaf ethyl acetate fraction extract, the P2 group received 250 mg/Kgbw/1mL/day, and the P3 group received 500 mg/Kgbw/1mL/day. Blood glucose levels were measured before and after alloxan administration, and then again on day 14. After 14 days of treatment, all rats were euthanized, and blood from the heart was collected to examine the insulin levels. To determine the differences between treatments, statistical analysis utilizing ANOVA was used, followed by Duncan's test. The findings revealed administered an ethyl acetate fraction of bay leaf can lower blood glucose and increased insulin levels in rats had hyperglycemia.

Elevated Growol Flour Reduce Fasting Blood Glucose, HOMA-IR and Increase Insulin Level in Rat Model with Type 2 Diabetes Mellitus

The rise of glucose levels in the blood of patients with type-2 diabetes mellitus (T2DM) is attributed to the decrease of insulin secretion and the interruption of insulin activity. Growol is a fermented product made from cassava that has the potential to lower blood glucose levels in patients with T2DM. This study was aimed to evaluate the effects of oral administration of growol flour on the levels of blood glucose, insulin, and HOMA-IR. A total of 40 male Wistar rats were divided into 5 groups i.e., negative control group, positive control group taking metformin, and 3 treatment groups taking growol flour of 3.1, 6.2, and 9.3 (g/200gBW), respectively, for 2 weeks. Blood glucose levels were measured using Enzymatic Photometric Method GOD-PAP, insulin using the ELISA kit, and HOMA-IR using the formula. The Shapiro Wilk test was used to determine the normality of the data followed by the One-Way ANOVA test and Posthoc Tukey HSD test. The Paired T-test was used to see the difference of pre- and post-treatment levels of blood glucose, insulin, and HOMA-IR. There was a decrease (p&lt;0.05) in blood glucose levels and HOMA-IR after the administration of low, moderate, and high doses of growol flour. In contrast, the levels of insulin increased (p&lt;0.05) after the administration of low, moderate, and high doses. In conclusion, growol flour contributes to the maintenance of T2DM by lowering the levels of fasting blood glucose levels, as well as HOMA-IR, and increasing the levels of insulin in rats.

Pharmacodynamic and pharmacokinetic interaction of losartan with glimepiride-metformin combination in rats and rabbits.

OBJECTIVES:The presence of comorbidities such as cardiovascular disease, peripheral vascular disease, and chronic renal disease, or and the prevention of these ailments in diabetics, frequently demands multiple drug treatments, increasing the risk of drug-drug interactions (DDIs). The current study was focused on identifying possible DDIs on concomitant administration of losartan, a drug used to regulate hypertension along with a combination of glimepiride + metformin, widely used to treat diabetes mellitus. Possible pharmacodynamic and pharmacokinetic interactions were observed for, following single-dose as well as multiple-dose treatment protocols in normal and alloxan-induced diabetes in albino Wistar rats and rabbits.MATERIALS AND METHODS:Blood samples from surviving rats/rabbits obtained through orbital venous sinus bleeding/marginal ear vein bleeding, respectively, at predetermined intervals and put through to biochemical estimations of sugar level in the blood by Glucose oxidase/peroxidase method; insulin levels in serum using the enzyme-linked immunosorbent assay and serum glimepiride levels using the high-performance liquid chromatography.RESULTS AND DISCUSSION:Losartan, when treated as a single drug, resulted in a slight lowering of blood glucose levels in normal rats, diabetic rats and normal rabbits. Hypoglycemic activity of a combination of glimepiride + metformin was enhanced when losartan was co-administered as a single dosage schedule as well as a multiple dose schedule as indicated by a reduced blood glucose level and enhanced levels of insulin in rats as well as in rabbits. Serum glimepiride levels were also higher and pharmacokinetic parameters of glimepiride including mean residence time, Cmax, T1/2, AUMC0-∞, AUMC0-t, and AUC0-∞, were significantly higher, whereas its clearance was decreased in the two regimens of losartan that was followed.CONCLUSION:It can therefore be concluded, that in diabetics with hypertension as a comorbidity condition, co-administration of losartan with glimepiride + metformin should be avoided or the dosage of a combination of glimepiride + metformin needs to be tittered to avoid recurrence of hypoglycemic episodes.

Renal mass reduction increases the response to exogenous insulin independent of acid-base status or plasma insulin levels in rats.

Impairments in insulin sensitivity can occur in patients with chronic kidney disease (CKD). Correction of metabolic acidosis has been associated with improved insulin sensitivity in CKD, suggesting that metabolic acidosis may directly promote insulin resistance. Despite this, the effect of acid or alkali loading on insulin sensitivity in a rodent model of CKD (remnant kidney) has not been directly investigated. Such studies could better define the relationship between blood pH and insulin sensitivity. We hypothesized that in remnant kidney rats, acid or alkali loading would promote loss of pH homeostasis and consequently decrease insulin sensitivity. To test this hypothesis, we determined the impact of alkali (2 wk) or acid (5-7 days) loading on plasma electrolytes, acid-base balance, and insulin sensitivity in either sham control rats, 2/3 nephrectomized rats, or 5/6 nephrectomized rats. Rats with 5/6 nephrectomy had the greatest response to insulin followed by rats with 2/3 nephrectomy and sham control rats. We found that treatment with 0.1 M sodium bicarbonate solution in drinking water had no effect on insulin sensitivity. Acid loading with 0.1 M ammonium chloride resulted in significant reductions in pH and plasma bicarbonate. However, acidosis did not significantly impair insulin sensitivity. Similar effects were observed in Zucker obese rats with 5/6 nephrectomy. The effect of renal mass reduction on insulin sensitivity could not be explained by reduced insulin clearance or increased plasma insulin levels. We found that renal mass reduction alone increases sensitivity to exogenous insulin in rats and that this is not acutely reversed by the development of acidosis.NEW & NOTEWORTHY Impairments in insulin sensitivity can occur in patients with chronic kidney disease, and previous work has suggested that metabolic acidosis may be the underlying cause. Our study investigated the effect of acid or alkali loading on insulin sensitivity in a rodent model of chronic kidney disease. We found that renal mass reduction increases the blood glucose response to insulin and that this is not acutely reversed by the development of acidosis.

The Influence of Acesulfame-K and Aspartame on Some Physiological Parameters in Male Albino Rats

Background: the easiest method of reducing calories is to replace the high caloric food products with sweetened ones. Aim of the work: this study aimed to determine the effects of acesulfame-k or aspartame on some physiological parameters in male albino rats. Materials and methods: we used thirty male albino rats of local strain weighing from 100 to120 gm. The period of the experiment was 30 days. The animals were divided into three groups; Group 1: control, Group 2: rats received acesulfame-k (15 mg/kg/day) and group 3: rats received aspartame (50 mg/kg/day). Results: there was an increase in serum glucose and insulin level in rats that received aspartame. In addition, there was increase in ASAT and ALAT activities, serum creatinine, serum urea and lipid profile except HDL-C in both treated groups as compared to the control group. Meanwhile, there was a drop in serum testosterone level and serum T3&T4 levels in aspartame group as well as in total protein, albumin and albumin/globulin ratio in both treated groups as compared to control group. Conclusion: aspartame has more dangerous effects than acesulfame-k.

A diet rich in menhaden oil has the hypolipidemic effect but increases plasma glucose and insulin levels in rats

A diet rich in menhaden oil has the hypolipidemic effect but increases plasma glucose and insulin levels in rats

Verapamil prevents the effect of calcium-sensing receptor activation on the blood glucose and insulin levels in rats.

The Ca2+ triggered insulin exocytosis in β cells of the pancreatic islets may be the result of Ca2+ influx through L-type voltage dependent calcium channels (VDCC) localized in the plasma membrane, as well as of liberation of Ca2+ from intracellular storages, induced by activation of the calcium receptor (CaR) coupled with the PLC enzyme present in the pancreatic islets. The present study was designated to determine, in in vivo experiments, the effects of CaR activation by R-568 and inhibition of the receptor by NPS 2143 on the plasma glucose and insulin levels in the presence of verapamil, a calcium channel blocker. Wistar rats, after fasting for 14 h before the experiment, were anesthetized with inactin and loaded ip with 1 g/kg glucose. In comparison to the control group, the verapamil-induced blockade of the calcium channels in glucose loaded animals increased the blood glucose level and decreased the insulin level, whereas CaR activation with R-568 induced opposite effects. However, in the presence of verapamil, R-568 did not change the concentration of glucose or insulin versus the control animals. Verapamil infusion did not alter elevated glucose concentration in the NPS 2143 animals. At the same time, verapamil reduced the plasma insulin level and potentiated the drop of insulin concentration induced by NPS 2143. The observations suggest that under the in vivo conditions, calcium channel blockade may prevent changes in the blood glucose and insulin concentrations induced by the CaR activation.

Activity of the calcium-sensing receptor influences blood glucose and insulin levels in rats.

The calcium-sensing receptor (CaR) has been found not only in parathyroid glands but also in other tissues, e.g. in β cells of the pancreatic islets. Therefore, CaR might likely mediate the mechanism of insulin secretion. The present study was designed to examine the in vivo effects of R-568, a CaR agonist, and NPS2143, a CaR inhibitor, on plasma insulin and blood glucose concentrations. Wistar rats, after fasting for 14h before the experiment, were anesthetized with inactin and loaded ip with 1g/kg glucose. 20, 120 and 180min after iv R-568 administration, plasma insulin increased markedly (by approximately 30%), in glucose-loaded rats, as compared to the control animals. Simultaneously, 180min after R-568 administration, a significant drop by approximately 12% in blood glucose was observed. In contrast, administration of R-568 in rats not given glucose, did not influence the blood glucose or plasma insulin concentrations vs. the control group. Administration of NPS2143 increased the blood glucose level markedly (by about 18% vs. control group) at 180 and 210min of the experiment. Simultaneously, a significant decrease of insulin concentration was observed vs. control group (by about 18 and 23%, respectively). We suggest that modulation of the CaR activity may participate in the mechanisms which mediate insulin secretion in rats.

Early Life Stress Increases Metabolic Risk, HPA Axis Reactivity, and Depressive-Like Behavior When Combined with Postweaning Social Isolation in Rats

Early-life stress is associated with depression and metabolic abnormalities that increase the risk of cardiovascular disease and diabetes. Such associations could be due to increased glucocorticoid levels. Periodic maternal separation in the neonate and rearing in social isolation are potent stressors that increase hypothalamus-pituitary-adrenal axis activity. Moreover, social isolation promotes feed intake and body weight gain in rats subjected to periodic maternal separation; however, its effects on metabolic risks have not been described. In the present study, we evaluated whether periodic maternal separation, social isolation rearing, and a combination of these two stressors (periodic maternal separation + social isolation rearing) impair glucose homeostasis and its relation to the hypothalamus-pituitary-adrenal axis and depressive-like behavior. Periodic maternal separation increased basal corticosterone levels, induced a passive coping strategy in the forced swimming test, and was associated with a mild (24%) increase in fasting glucose, insulin resistance, and dyslipidemia. Rearing in social isolation increased stress reactivity in comparison to both controls and in combination with periodic maternal separation, without affecting the coping strategy associated with the forced swimming test. However, social isolation also increased body weight gain, fasting glucose (120%), and insulin levels in rats subjected to periodic maternal separation. Correlation analyses showed that stress-induced effects on coping strategy on the forced swimming test (but not on metabolic risk markers) are associated with basal corticosterone levels. These findings suggest that maternal separation and postweaning social isolation affect stress and metabolic vulnerability differentially and that early-life stress-related effects on metabolism are not directly dependent on glucocorticoid levels. In conclusion, our study supports the cumulative stress hypothesis, which suggests that metabolic risk markers arise when vulnerable individuals are exposed to social challenges later in life.

Abscisic Acid Stimulates Glucagon-Like Peptide-1 Secretion from L-Cells and Its Oral Administration Increases Plasma Glucagon-Like Peptide-1 Levels in Rats.

In recent years, Abscisic Acid (ABA) has been demonstrated to be involved in the regulation of glucose homeostasis in mammals as an endogenous hormone, by stimulating both insulin release and peripheral glucose uptake. In addition, ABA is released by glucose- or GLP-1-stimulated β-pancreatic cells. Here we investigated whether ABA can stimulate GLP-1 release. The human enteroendocrine L cell line hNCI-H716 was used to explore whether ABA stimulates in vitro GLP-1 secretion and/or transcription. ABA induced GLP-1 release in hNCI-H716 cells, through a cAMP/PKA-dependent mechanism. ABA also enhanced GLP-1 transcription. In addition, oral administration of ABA significantly increased plasma GLP-1 and insulin levels in rats. In conclusion, ABA can stimulate GLP-1 release: this result and the previous observation that GLP-1 stimulates ABA release from β -cells, suggest a positive feed-back mechanism between ABA and GLP-1, regulating glucose homeostasis. Type 2 diabetes treatments targeting the GLP-1 axis by either inhibiting its rapid clearance by dipeptidyl-peptidase IV or using GLP-1 mimetics are currently used. Moreover, the development of treatments aimed at stimulating GLP-1 release from L cells has been considered as an alternative approach. Accordingly, our finding that ABA increases GLP-1 release in vitro and in vivo may suggest ABA and/or ABA analogs as potential anti-diabetic treatments.

A protective role of arecoline hydrobromide in experimentally induced male diabetic rats.

Objectives. Arecoline, the most potent and abundant alkaloid of betel nut, causes elevation of serum testosterone and androgen receptor expression in rat prostate, in addition to increase in serum insulin levels in rats, leading to insulin resistance and type 2 diabetes-like conditions. This study investigated the role of arecoline on the reproductive status of experimentally induced type 1 diabetic rats. Methods. Changes in the cellular architecture were analyzed by transmission electron microscopy. Blood glucose, serum insulin, testosterone, FSH, and LH were assayed. Fructose content of the coagulating gland and sialic acid content of the seminal vesicles were also analyzed. Results. Arecoline treatment for 10 days at a dose of 10 mg/kg of body weight markedly facilitated β-cell regeneration and reversed testicular and sex accessory dysfunctions by increasing the levels of serum insulin and gonadotropins in type 1 diabetic rats. Critical genes related to β-cell regeneration, such as pancreatic and duodenal homeobox 1 (pdx-1) and glucose transporter 2 (GLUT-2), were found to be activated by arecoline at the protein level. Conclusion. It can thus be suggested that arecoline is effective in ameliorating the detrimental effects caused by insulin deficiency on gonadal and male sex accessories in rats with type 1 diabetes.

Feeding Soy with Probiotic Attenuates Obesity-Related Metabolic Syndrome Traits in Obese Zucker Rats

Obesity has reached pandemic levels, being a major concern of health. Overweight and obesity are the precursors for metabolic disturbances in the body. Probiotics and prebiotics administrations have shown to reduce the characteristics of obesity-induced metabolic syndrome in animals. The present study examined the effects of dietary supplementation of soybean meal and Bifidobacterium longum (BB536) singly and in combination on obesity-related traits in obese Zucker rats. Control group rats were fed with AIN93-M diet and treatment groups were fed with soybean meal (5 % or 10%) and Bifidobacterium longum (0.1%) in single and combinations for 100 days. Weight gain, feed intake, and % of fat in liver were recorded. Serum biochemical parameters such as cholesterol, triglycerides, insulin and glucose were analyzed. Activities of liver enzymatic markers (alanine aminotransferase (ALT), gamma glutamyl-transferase (GGT), and alkaline phosphatase (ALP)) were determined. Dietary supplementation of soymeal at 10% with B. longum reduced the weight gain by 30% and liver fat content by 35%. Feeding Bifidobacterium longum alone did not have any effect in analyzing serum biochemical parameters and activity of liver enzymatic markers. Serum glucose and insulin levels in rats were lowered by 18% - 24% and 22% - 25% respectively when fed with administration of combinational feeding of soymeal at 5% and 10% with Bifidobacterium longum. Hepatic enzyme activity was reduced by 1.3 fold with the combinational diet at higher concentration (soy 10%). The present study provides evidence that supplementation with soymeal with probiotic, B. longum attenuates the metabolic disorders induced by obesity in obese Zucker rats.

The effect of a swim workout program along with the use of arbutin on glucose and insulin levels in rats with hyperglycemia

Arbutin has antioxidant effects that cause to reduce glucose levels. There is little information about the effect of swim workout along with arbutin on glucose and insulin level. Hence, objective of the present research is to investigate the effect of a swim workout program with the use of arbutin on glucose and insulin levels in rats with hyperglycemia. Experimental study was done on 28 adult male Wistar rats and after the injection of alloxan and becoming diabetic, they were divided into four groups including control, receiving arbutin, receiving arbutin + swimming and swim workout. Swim workout protocol for was conducted for 6 weeks, 5 days a week. Data were analyzed using ANOVA and dependent t-tests. After 6 weeks, blood glucose levels had a significant decrease in groups of swim workout, receiving arbutin + swim workout (p=0.02). On the other hand, mean insulin levels were significantly reduced in swim workout group (p=0.01), and no significant difference was observed between other groups. The results of present research suggest that, a swim workout course along with the use of arbutin have their own positive effect on glucose and insulin levels in mice infected with Hyperglycemia, also aerobic workout showed more effectiveness.

The effects of selected hot and cold temperament herbs based on Iranian traditional medicine on some metabolic parameters in normal rats.

This study was aimed to evaluate the effects of diets containing some hot and cold temperament herb seeds according to Iranian traditional medicine (ITM) on some metabolic parameters in acute (24 h) and sub-acute (7 day) experiments that were performed on rats. For each experiment, effects of diets containing 10% herb seeds in category of hot (anise, fennel, ajowan) and cold (cucumber, watermelon, pumpkin) temperaments were analyzed on body weight gain, food intake, water consumption, urine output, serum glucose (SG) and insulin levels of rats. In the acute experiment, anise or fennel fed groups showed a significant decrease in food intake and there were not any changes in other parameters. The hot temperament groups in comparison with the cold temperament ones showed a significant decrease in food intake and a significant increase in SG level. In the sub-acute experiment, anise and fennel fed groups had a significant decrease in body weight gain on the 4thday. On the 7th day, the anise fed group experienced a significant decrease in body weight gain and a significant increase in SG levels. The groups that were fed hot temperament diets compared to the ones that consumed cold temperament diets showed a significant decrease in body weight gain and food intake rates and a considerable increase in SG levels. Considering the findings of this study, one can conclude that it is possible that hot temperament herbs such as anise and fennel be useful for humans for certain conditions such as weight control.

Comparison of in vivo effects of insulin on SREBP-1c activation and INSIG-1/2 in rat liver and human and rat adipose tissue

The stimulatory effects of insulin on de novo lipogenesis (DNL) in the liver, where it is an important contributor to non-alcoholic fatty liver disease (NAFLD), hepatic and systemic insulin resistance, is strong and well established. In contrast, insulin plays only a minor role in DNL in adipose tissue. The reason why insulin stimulates DNL more in liver than in fat is not known but may be due to differential regulation of the transcription and post-translational activation of sterol regulatory element binding proteins (SREBPs). To test this hypothesis, we have examined effects of insulin on activation of SREBP-1c in liver of rats and in adipose tissue of rats and human subjects. Liver and epidydimal fat were obtained from alert rats and subcutaneous adipose tissue from human subjects in response to 4 h euglycemic-hyperinsulinemic clamps.Here we show that acutely raising plasma insulin levels in rats and humans increased SREBP-1 mRNA comparably 3-4 fold in rat liver and rat and human adipose tissue, but increased post-translational activation of SREBP-1c only in rat liver, while decreasing it in adipose tissue. These differential effects of insulin on SREBP-1c activation in liver and adipose tissue were associated with robust changes in the opposite direction of INSIG-1 and to a lesser extent of INSIG-2 mRNA and proteins.We conclude that these findings support the hypothesis that insulin stimulated activation of SREBP-1c in the liver, at least in part, by suppressing INSIG-1 and -2, whereas in adipose tissue, an increase in INSIG-1 and -2 prevented SREBP-1c activation.

May rye bread enriched with green tea extract be useful in the prevention of obesity in rats?

We examined the hypothesis that rye bread enriched with green tea extract (GTE) (at two different doses) can prevent obesity as a component of a hypercaloric diet by decreasing the absorption of energy providing nutrients and regulating lipid metabolism-related hormones, in comparison with normal caloric diet used in the Wistar rats. Adult male Wistar rats were divided into 4 groups: group ND received a normal caloric diet, group HRB received a hypercaloric diet with control rye bread, groups HRB0.8% and HRB1.1% received a hypercaloric diet with rye bread enriched with 0.8% and 1.1% GTE, respectively. Higher food intake in the ND group compared with the other groups of rats was noted; however, there was no statistical difference in the energy intake among any of the groups. Consumption of the hypercaloric diet increased the body weight of the rats (in comparison with ND), but rats from HRB1.1% group showed a tendency towards smaller gains in body weight (∼4.0%) when compared to the HRB group. The addition of 1.1% GTE to rye bread resulted in an increase in the energy content of faeces, compared to both HRB and ND groups. No differences were observed in plasma leptin concentrations between the four groups. The insulin level in rats fed a hypercaloric diet was higher in comparison to rats from the ND group. The consumption of rye bread enriched with 1.1% GTE may increase faeces energy excretion, but without significantly suppressing body weight gain, visceral fat accumulation, or changing biochemical parameters related to lipid metabolism.

Impact of ADMA (asymmetric dimethylarginine) on physiology with respect to diabetes mellitus and respiratory system BEAS-2B cells (human bronchial epithelial cells)

Asymmetric dimethylarginine (ADMA) is a non-selective nitric oxide (NO) synthase inhibitor associated with cardiovascular and metabolic disorders. This study aimed to investigate ADMA with respect to both diabetes and respiratory disease. Glucose was determined by hexokinase method, insulin by a radioimmunoassay. Griess test was used for NO assay and cytokinines were assayed by ELISA. Ciliary beat frequency was determined by high speed video using a microscope. ADMA induced an increase in blood glucose and plasma insulin levels in rats; the ratio of these effects indicates the induction of a diabetic situation (insulin resistance). L-arginine increased blood glucose and initially slightly decreased plasma insulin. A pretreatment with ADMA abolished these effects. ADMA shows similar effects in vitro (insulin-secreting cell line, INS-1 cells). L-arginine increased production of NO, which was reversed by ADMA (INS-1 cells). ADMA also reduced NO production positively modulated by various substances, namely metformin, ciglitazone, losartan and nateglinide, but nevertheless inhibited insulin release induced by these compounds. ADMA stimulated the production of cytokines such as interleukin (IL-6) and macrophage inflammatory protein-2 (MIP-2) (rat IL-8 analogue) from INS-1 cells. 5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), a direct adenosine monophosphate protein kinase (AMPK) activator and anti-inflammatory agent, induced NO production and reduced cytokine release. In contrast to diabetes parameters, ADMA had no effect of on the respiratory system (cytokine secretion from BEAS-2B cells (IL-8, regulated on activation, normal T cell expressed and secreted, and tumour necrosis factor-α), ciliary beat frequency and smooth muscle contraction of rat trachea). ADMA has a pathophysiological impact leading to a diabetic situation but has no impact on the respiratory system.

A New view of Insulin Action

Insulin not only stimulates the Na-K-pump,but by stimulating the Na:H exchange pump increases intracellular pH, pHi. Fidelman et al (1982) found, as predicted by thermodynamic theory, the effect of insulin on glycolysis varied linearly with log[Na]o with the insulin effect being converted from stimulation of glycolysis to a 51% inhibition at 0.12 mM Nao.Zierler & Rabinowitz (1964) demonstrated in the forearm of human males that levels of insulin too low to affect glucose uptake, as little as 38 micro units per ml, was sufficient to stimulate the Na-K-pump, as reflected by increased potassium uptake, while producing no effect upon glucose uptake. This one experiment forces us to realize that the main action of insulin is not to regulate blood glucose levels, but to regulate the Na-K-pump and Na:H exchange. Since the Na-K-pump uses about 25% of the ATP production in a resting muscle, stimulation of the Na-K-pump increases the consumption of ATP so much that at high levels of stimulation, it is necessary to get more glucose into the cell to manufacture more ATP.Since insulin decreases Nai, elevates pHi, and increases production of ATP, one would expedt that the decreased insulin, such as seen in diabetes or in fasting would result in the reverse of these changes. Lowering plasma levels of insulin in rats by small doses of streptozotocin or by fasting produced an increase in Nai of about 30%, a decrease in pHi of 0.15 units, and a 24% decrease in ATPi.The action of thiazide diuretics to cause type 2 diuretics has been shown to be due to their ability to cause potassium loss. Not surprisingly, diets with large amounts of potassium and small amounts of sodium have been shown to reverse diabetes.