Insulin modulates inflammatory and repair responses to elastase-induced emphysema in diabetic rats

As pulmonary emphysema and diabetes mellitus are common diseases, concomitance of both is correspondingly expected to occur frequently. To examine whether insulin influences the development of inflammation in the alveolar septa, diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., n = 37) and matching controls (n = 31) were used. Ten days after alloxan injection, diabetic and control rats were instilled with physiologic saline solution containing porcine pancreatic elastase (PPE, 0.25 IU/0.2 ml, right lung) or saline only (left lung). The following analyses were performed: (i) number of leucocytes in the bronchoalveolar lavage (BAL) fluid of the animals, 6 h after PPE/saline instillation (early time point); and (ii) mean alveolar diameter (μm) and quantification of elastic and collagen fibres (%) 50 days after PPE/saline instillation (late time point). Relative to controls, alloxan-induced diabetic rats showed a 42% reduction in the number of neutrophils in BAL fluid, a 20% increase in the mean alveolar diameter and a 33% decrease in elastic fibre density in the alveolar septa. Treatment of diabetic rats with 4 IU neutral protamine Hagedorn (NPH) insulin, 2 h before elastase instillation, restored the number of neutrophils in the BAL fluid. The mean alveolar diameter and elastic fibre content in alveolar septa matched the values observed in control rats if diabetic rats were treated with 4 IU NPH insulin 2 h before instillation followed by 2 IU/day for the next 50 days. Density of collagen fibres did not differ between the various groups. Thus, the data presented suggest that insulin modulates the inflammatory and repair responses in elastase-induced emphysema, and assures normal repair and tissue remodelling.     

Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats.

Heart failure is known to be a complication of insulin-dependent (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) even in the absence of coronary heart disease or hypertension. The mechanisms leading to diabetic cardiomyopathy are unknown. The aim of the study was to characterize structural and functional alterations in hyperinsulinemic Zucker diabetic fatty (ZDF) rats treated with or without insulin. Diabetic animals showed a twofold increase in cardiomyocyte volume with increased left ventricular ANP but not BNP mRNA levels in spite of a reduced plasma renin activity (PRA) 2 months after onset of diabetes compared to nondiabetic littermates. These changes were associated with an increase in left ventricular performance as assessed by echocardiography. Insulin treatment led to a significant increase in body weight (BW), total heart weight, myocardial protein content, and left ventricular mass (LVM). Perivascular fibrosis and laminin thickness were significantly augmented in diabetic rat myocardium irrespective of insulin treatment, whereas interstitial collagen I and fibronectin were similarly found in diabetic and control myocardium. Initial stages of diabetic cardiomyopathy in hyperinsulinemic rats are characterized by cardiomyocyte hypertrophy and enhanced cardiac contractility. It is suggested that hyperinsulinemia may be involved in cardiac hypertrophy.     

TCF7L2 genetic variants and progression to diabetes in the Chinese population: pleiotropic effects on insulin secretion and insulin resistance

TCF7L2 genetic variants were associated with progression to type 2 diabetes in Europeans. However, the role of TCF7L2 in type 2 diabetes remained uncertain in Chinese. Seventeen tag single nucleotide polymorphisms were genotyped in 1,094 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study. At baseline, the rs7903146 T allele in the exon 4 linkage disequilibrium (LD) block were associated with lower insulinogenic index at 60 min (P = 0.01), while the rs290481 G allele near the 3′ end was associated with higher 2-h post-challenge glucose (P = 0.003) and insulin concentration (P = 0.02), elevated systolic (P = 0.01) and diastolic blood pressure (P = 0.006), lower waist circumference (P = 0.01), and increased steady-state plasma glucose (SSPG) concentration measured with modified insulin suppression test (P = 0.02). Over an average follow-up period of 5.43 years, participants with the rs7903146 T allele or variants in the same LD block, but not those with the rs290481 G allele, were more likely to progress to diabetes (hazard ratio = 2.61, 95% confidence interval, 1.27–5.39, P = 0.009) than were non-carriers. TCF7L2 gene expression was inversely associated with SSPG in human visceral (r = −0.73, P = 0.006) and subcutaneous adipose tissue (r = −0.62, P = 0.03). TCF7L2 may exert pleiotropic effects on insulin secretion or insulin resistance. However, only variants associated with impaired β-cell function predict progression to diabetes in Chinese.     

Oxidative and proteolysis‐related parameters of skeletal muscle from hamsters with experimental pulmonary emphysema: a comparison between papain and elastase induction

The objective of this study was to investigate whether emphysema induced by elastase or papain triggers the same effects on skeletal muscle, related to oxidative stress and proteolysis, in hamsters. For this purpose, we evaluated pulmonary lesions, body weight, muscle loss, oxidative stress (thiobarbituric acid‐reactive substances, total and oxidized glutathiones, chemiluminescence stimulated by tert‐butyl hydroperoxide and carbonyl proteins), chymotrypsin‐like and calpain‐like proteolytic activities and muscle fibre cross‐sectional area in the gastrocnemius muscles of emphysemic hamsters. Two groups of animals received different intratracheal inductions of experimental emphysema: by 40 mg/ml papain (EP) or 5.2 IU/100 g animal (EE) elastase (n = 10 animals/group). The control group received intratracheal instillation of 300 μl sterile NaCl 0.9%. Compared with the control group, the EP group had reduced muscle weight (18.34%) and the EE group had increased muscle weight (8.37%). Additionally, tert‐butyl hydroperoxide‐initiated chemiluminescence, carbonylated proteins and chymotrypsin‐like proteolytic activity were all elevated in the EP group compared to the CS group, while total glutathione was decreased compared to the EE group. The EE group showed more fibres with increased cross‐sectional areas and increased calpain‐like activity. Together, these data show that elastase and papain, when used to induce experimental models of emphysema, lead to different speeds and types of adaptation. These findings provide more information on choosing a suitable experimental model for studying skeletal muscle adaptations in emphysema.     

Higher sleep variability is associated with poorer glycaemic control in patients with type 1 diabetes

Sleep disturbances have been linked to insulin resistance and poor glycaemic control in patients with type 2 diabetes. However, the data are limited in type 1 diabetes. Recently, varying day‐to‐day sleep schedules, i.e. sleep variability, have been associated with adverse metabolic profile in healthy individuals. This study explored whether sleep variability affects glycaemic control and insulin requirement in type 1 diabetes. Forty‐one adult patients with type 1 diabetes wore an actigraphy for 5 nights. Standard deviation of sleep duration, efficiency and mid‐sleep time were sleep variability parameters. Sleep apnoea risk and self‐reported sleep quality were assessed by the Berlin questionnaire and Pittsburgh Sleep Quality Index. Haemoglobin A1c, diabetes complications and insulin regimen were obtained from medical records. After adjusting for neuropathic symptoms, sleep apnoea risk and poor self‐reported sleep quality, higher sleep variability was significantly associated with poorer glycaemic control (standard deviation of sleep duration, B = 0.100, P = 0.004; and standard deviation of mid‐sleep time, B = 0.068, P = 0.04). In addition, standard deviations of sleep duration and mid‐sleep time were highly correlated, suggesting that participants changed their sleep duration along with sleep timing. After adjusting for covariates, the standard deviation of sleep duration (P = 0.009) and standard deviation of mid‐sleep time (P = 0.012) were associated with higher insulin requirement. In summary, higher sleep variability, which likely reflects sleep deprivation alternating with sleep compensation along with shifts in their circadian timing, was associated with poorer glycaemic control and higher insulin requirement in patients with type 1 diabetes. Increased sleep regularity may improve metabolic control in type 1 diabetes.     

Cerium oxide nanoparticles attenuate monocrotaline induced right ventricular hypertrophy following pulmonary arterial hypertension

Cerium oxide (CeO₂) nanoparticles have been posited to exhibit potent anti-oxidant activity which may allow for the use of these materials in biomedical applications. Herein, we investigate whether CeO₂ nanoparticle administration can diminish right ventricular (RV) hypertrophy following four weeks of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male Sprague Dawley rats were randomly divided into three groups: control, MCT only (60 mg/kg), or MCT + CeO₂ nanoparticle treatment (60 mg/kg; 0.1 mg/kg). Compared to the control group, the RV weight to body weight ratio was 45% and 22% higher in the MCT and MCT + CeO₂ groups, respectively (p < 0.05). Doppler echocardiography demonstrated that CeO₂ nanoparticle treatment attenuated monocrotaline-induced changes in pulmonary flow and RV wall thickness. Paralleling these changes in cardiac function, CeO₂ nanoparticle treatment also diminished MCT-induced increases in right ventricular (RV) cardiomyocyte cross sectional area, β-myosin heavy chain, fibronectin expression, protein nitrosylation, protein carbonylation and cardiac superoxide levels. These changes with treatment were accompanied by a decrease in the ratio of Bax/Bcl2, diminished caspase-3 activation and reduction in serum inflammatory markers. Taken together, these data suggest that CeO₂ nanoparticle administration may attenuate the hypertrophic response of the heart following PAH.     

Long‐term dexamethasone treatment alters the histomorphology of acinar cells in rat parotid and submandibular glands

Glucocorticoids (GCs) induce insulin resistance (IR), a condition known to alter oral homeostasis. This study investigated the effects of long‐term dexamethasone administration on morphofunctional aspects of salivary glands. Male Wistar rats received daily injections of dexamethasone [0.1 mg/kg body weight (b.w.), intraperitoneally] for 10 days (DEX), whereas control rats received saline. Subsequently, glycaemia, insulinaemia, insulin secretion and salivary flow were analysed. The parotid and submandibular glands were collected for histomorphometric evaluation and Western blot experiments. The DEX rats were found to be normoglycaemic, hyperinsulinaemic, insulin resistant and glucose intolerant (P < 0.05). DEX rat islets secreted more insulin in response to glucose (P < 0.05). DEX rats had significant reductions in the masses of the parotid (29%) and submandibular (16%) glands (P < 0.05) that was associated with reduced salivary flux rate. The hypotrophy in both glands observed in the DEX group was associated with marked reduction in the volume of the acinar cells in these glands of 50% and 26% respectively (P < 0.05). The total number of acinar cells was increased in the submandibular glands of the DEX rats (P < 0.05) but not in the parotid glands. The levels of proteins related to insulin and survival signalling in both glands did not differ between the groups. In conclusion, the long‐term administration of dexamethasone caused IR, which was associated with significant reductions in both mass and flux rate of the salivary glands. The parotid and submandibular glands exhibited reduced acinar cell volume; however, the submandibular glands displayed acinar hyperplasia, indicating a gland‐specific response to GCs. Our data emphasize that GC‐based therapies and insulin‐resistant states have a negative impact on salivary gland homeostasis.     

Hyperglycaemia alters the endothelium‐dependent relaxation of canine coronary arteries

The aim of the present study was to investigate the effects of experimental diabetes and hyperglycaemia per se on the endothelium‐dependent relaxation of isolated canine coronary arteries and to analyse the possible involvement of the cyclooxygenase pathway in the alterations induced by hyperglycaemia. Rings from the left anterior descending coronary arteries of 18 metabolically healthy, six alloxan‐diabetic and six insulin‐treated alloxan diabetic dogs were set up for isometric tension recording. Diabetic coronaries as well as healthy vessels subjected to in vitro hyperglycaemia (25.5 mmol L^–1 glucose) showed impaired (P < 0.05) relaxation to acetylcholine (3 nmol L^–1–10 μmol L^–1) compared with normoglycaemic, i.e. metabolically healthy and insulin‐treated diabetic controls, either before or after indomethacin (3 μmol L^–1) administration. The maximal dilation elicited by acetylcholine was further decreased (P < 0.05) by the cyclooxygenase inhibitor in the diabetic coronaries only. Relaxation to sodium nitroprusside did not differ among groups. These results suggest that hyperglycaemia may result in impaired endothelium‐dependent dilation of coronary arteries. Diminished relaxation of diabetic coronaries is worsened by the inhibition of the synthesis of vasodilator cyclooxygenase products.     

Maternal use of flaxseed oil during pregnancy and lactation prevents morphological alterations in pancreas of female offspring from rat dams with experimental diabetes

Nutritional recommendations have promoted the increased need to consume n‐3 polyunsaturated fatty acids. Flaxseed is the richest dietary source of n‐3 fatty acids among plant sources and is widely used for its edible oil. This study aimed to investigate whether maternal use of flaxseed oil has effects on pancreas morphology in the female offspring of diabetic mothers. Female Wistar rats (n = 12) were induced into diabetes by a high‐fat diet and low dose of streptozotocin. After confirmation of the diabetes, rats were mated, and once pregnancy was confirmed, they were allocated into three groups (n = 6): high‐fat group (HG); flaxseed oil group (FOG); and control group (CG) (non‐diabetic rats). At weaning, female offspring (n = 6/group) received standard chow diet. The animals were euthanized at 180 days. Pancreas was collected for histomorphometric and immunohistochemistry analysis. HG showed hypertrophy of pancreatic islets (P < 0.0001), whereas FOG offspring had islets with smaller diameters compared to HG (P < 0.0001). HG offspring showed higher percentage of larger (P = 0.0061) and lower percentage of smaller islets (P = 0.0036). HG showed lower islet insulin immunodensity at 180 days (P < 0.0001), whereas FOG was similar to CG (P < 0.0001). Flaxseed oil reduced the damage caused by maternal hyperglycaemia, promoting normal pancreas histomorphometry and β‐cell mass in female offspring.     

Preventive aerobic training exerts a cardioprotective effect on rats treated with monocrotaline

Pulmonary arterial hypertension (PAH) is a chronic disease which causes overload to the right ventricle. The effect of preventive training on cardiac remodelling in this condition is still unknown. This study aimed to evaluate the influence of preventive training on hypertrophy, heart function and gene expression of calcium transport proteins in rats with monocrotaline‐induced PAH. Thirty‐two male Wistar rats were randomly divided into four groups: S, sedentary control; T, trained control; SM, sedentary monocrotaline; and TM, trained monocrotaline. The preventive training protocol was performed on a treadmill for 13 weeks, five times/week. The first two weeks were adopted for adaptation to training with gradual increases in speed/time. The speed of the physical training from the third to tenth weeks was gradually increased from 0.9 to 1.1 km/h for 60 min. Next, monocrotaline was applied (60 mg/kg) to induce PAH and lactate threshold analysis performed to determine the training speeds. The training speed of the TM group in the following two weeks was 0.8 km/h for 60 min and the T = 0.9 km/h for 60 min; in the final two weeks, both groups trained at the same speed and duration 0.9 km/h, 60 min. Cardiac function was assessed through echocardiography, ventricular hypertrophy through histomorphometric analysis and gene expression through RT‐qPCR. Right cardiac function assessed through the peak flow velocity was SM = 75.5 cm/s vs. TM = 92.0 cm/s (P = 0.001), and ventricular hypertrophy was SM = 106.4 μm² vs. TM = 77.7 μm² (P = 0.004). There was a decrease in the gene expression of ryanodine S = 1.12 au vs. SM = 0.60 au (P = 0.02) without alterations due to training. Thus, we conclude that prior physical training exerts a cardioprotective effect on the right ventricle in the monocrotaline rat model.     

Tissue-specific reduction of galanin content in the pancreas in alloxan diabetes in the mouse

Galanin inhibits insulin secretion and has been proposed to function as a sympathetic neurotransmitter in the endocrine pancreas in some species, for example in the dog. In this study, pancreatic and adrenal gland galanin content were measured following experimental diabetes induced by alloxan in mice. Three days after administration of alloxan (70mgkg^-1, i.p.) in normal mice, pancreatic content of galanin-like immunoreactivity (GLIR) was reduced to 65 ± 11 % of that in untreated controls (P < 0.01), whereas adrenal gland GLIR was unchanged. Similarly, 8 days after alloxan administration, pancreatic GLIR was reduced (P < 0.002), whereas adrenal gland GLIR was unaffected. Pancreatic GLIR also inversely correlated with plasma glucose levels (r = -0.5055, P < 0.005). To distinguish between the direct effects of alloxan vs. indirect metabolic effects induced by the drug, alloxan-diabetic mice were treated with insulin twice daily, which normalized the plasma glucose levels (7.6 ± 0.3 mmol l^-1). Pancreatic GLIR was then not significantly different from controls. Thus pancreatic but not adrenal gland GLIR content is reduced in alloxan-induced diabetes in mice. The data support a role for galanin as a pancreatic sympathetic neurotransmitter which may participate in the metabolic alterations seen in alloxan diabetes in mice.     

Oxidative status and chymotrypsin-like activity in right and left ventricle hypertrophy in an experimental model of emphysema

Although cardiac muscle hypertrophy has been studied in association with several diseases, its mechanism in patients with emphysema, in particular in relation to oxidative stress and proteolysis, remains unknown. The role of oxidative stress and proteolysis in right and left ventricle hypertrophy was investigated in hamsters with emphysema induced by 2 different doses of papain (20 mg/mL, E20 and 40 mg/mL, E40). The thickness of the ventricles, total and cardiac weight, lipid peroxidation, carbonyl proteins, total antioxidant capacity (TAC), and proteasomal proteolytic activity were evaluated in the right ventricle (RV) and the left ventricle (LV) of control and emphysema hamsters. RV thickness was increased by 12% in the E20 group and by 29% in the E40 group. Lipid peroxidation measured by chemiluminescence was increased in the E40 group (from 3350.68 ± 392.44 URL/g tissue to 4696.63 ± 1076.70 URL/g tissue, p < 0.05). TAC also increased only in the E40 group. In the LV, chemiluminescence values increased from 4044.77 ± 503.39 to 5517.10 ± 388.27 in the E20 group and to 8169.14 ± 1748.77 URL/g tissue in the E40 group (p < 0.05, both). TAC significantly increased in the E20 and E40 groups. No differences were detected in substances reactive to thiobarbituric acid or carbonyl proteins when comparing ventricles or doses. Chymotrypsin-like proteolytic activity significantly decreased in both groups and ventricles. Emphysema can induce right and left ventricle lipid peroxidation and result in antioxidant mobilization. These data together support the idea that cardiac hypertrophy in response to emphysema is mediated in part by proteolytic pathways with involvement of reactive species.     

Antibodies to Influenza Virus A/H1N1 Hemagglutinin in Type 1 Diabetes Children Diagnosed Before,During and After the SWEDISH A(H1N1)pdm09 Vaccination Campaign 2009–2010

We determined A/H1N1‐hemagglutinin (HA) antibodies in relation to HLA‐DQ genotypes and islet autoantibodies at clinical diagnosis in 1141 incident 0.7‐to 18‐year‐old type 1 diabetes patients diagnosed April 2009–December 2010. Antibodies to ³⁵S‐methionine‐labelled A/H1N1 hemagglutinin were determined in a radiobinding assay in patients diagnosed before (n = 325), during (n = 355) and after (n = 461) the October 2009–March 2010 Swedish A(H1N1)pdm09 vaccination campaign, along with HLA‐DQ genotypes and autoantibodies against GAD, insulin, IA‐2 and ZnT8 transporter. Before vaccination, 0.6% patients had A/H1N1‐HA antibodies compared with 40% during and 27% after vaccination (P < 0.0001). In children <3 years of age, A/H1N1‐HA antibodies were found only during vaccination. The frequency of A/H1N1‐HA antibodies during vaccination decreased after vaccination among the 3 < 6 (P = 0.006) and 13 < 18 (P = 0.001), but not among the 6 < 13‐year‐olds. HLA‐DQ2/8 positive children <3 years decreased from 54% (15/28) before and 68% (19/28) during, to 30% (9/30) after vaccination (P = 0.014). Regardless of age, DQ2/2; 2/X (n = 177) patients had lower frequency (P = 0.020) and levels (P = 0.042) of A/H1N1‐HA antibodies compared with non‐DQ2/2; 2/X (n = 964) patients. GADA frequency was 50% before, 60% during and 51% after vaccination (P = 0.009). ZnT8QA frequency increased from 30% before to 34% during and 41% after vaccination (P = 0.002). Our findings suggest that young (<3 years) along with DQ2/2; 2/X patients were low responders to Pandemrix^®. As the proportion of DQ2/8 patients <3 years of age decreased after vaccination and the frequencies of GADA and ZnT8QA were enhanced, it cannot be excluded that the vaccine affected clinical onset of type 1 diabetes.     

Antihyperlipidemic and antiperoxidative effect of Diasulin,a polyherbal formulation in alloxan induced hyperglycemic rats

Background  

This study was undertaken to investigation the effect of Diasulin, a poly herbal drug composed of ethanolic extract of ten medicinal plants on blood glucose, plasma insulin, tissue lipid profile, and lipidperoxidation in alloxan induced diabetes.     

Doubly Reactive INS‐IGF2 Autoantibodies in Children with Newly Diagnosed Autoimmune (type 1) Diabetes

The splice variant INS‐IGF2 entails the preproinsulin signal peptide, the insulin B‐chain, eight amino acids of the C‐peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS‐IGF2 autoantibodies (INS‐IGF2A) were related to age at diagnosis, islet autoantibodies, HLA‐DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0–18 years of age, diagnosed with type 1 diabetes in 1996–2005 and controls (n = 363) were analysed for specific INS‐IGF2A after displacement with both cold insulin and INS‐IGF2 to correct for non‐specific binding and identify double reactive sera. GADA, IA‐2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA‐DQ genotypes were also determined. The median level of specific INS‐IGF2A was higher in patients than in controls (P < 0.001). Irrespective of age at diagnosis, 19% (126/676) of the patients had INS‐IGF2A when the cut‐off was the 95th percentile of the controls (P < 0.001). The risk of INS‐IGF2A was increased among HLA‐DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA‐DQ2/8 suggests that this autoantigen may be presented on HLA‐DQ trans‐heterodimers, rather than cis‐heterodimers. Autoantibodies reactive with both insulin and INS‐IGF2A at diagnosis support the notion that INS‐IGF2 autoimmunity contributes to type 1 diabetes.     

High-intensity exercise and carbohydrate-reduced energy-restricted diet in obese individuals

Continuous high glycemic load and inactivity challenge glucose homeostasis and fat oxidation. Hyperglycemia and high intramuscular glucose levels mediate insulin resistance, a precursor state of type 2 diabetes. The aim was to investigate whether a carbohydrate (CHO)-reduced diet combined with high-intensity interval training (HIIT) enhances the beneficial effects of the diet alone on insulin sensitivity and fat oxidation in obese individuals. Nineteen obese subjects underwent 14 days of CHO-reduced and energy-restricted diet. Ten of them combined the diet with HIIT (4 min bouts at 90% VO_2peak up to 10 times, 3 times a week). Oral glucose insulin sensitivity (OGIS) increased significantly in both groups; [diet–exercise (DE) group: pre 377 ± 70, post 396 ± 68 mL min⁻¹ m⁻²; diet (D) group: pre 365 ± 91, post 404 ± 87 mL min⁻¹ m⁻²; P < 0.001]. Fasting respiratory exchange ratio (RER) decreased significantly in both groups (DE group: pre 0.91 ± 0.06, post 0.88 ± 0.06; D group: pre 0.92 ± 0.07, post 0.86 ± 0.07; P = 0.002). VO_2peak increased significantly in the DE group (pre 27 ± 5, post 32 ± 6 mL kg⁻¹ min⁻¹; P < 0.001), but not in the D group (pre 26 ± 9, post 26 ± 8 mL kg⁻¹ min⁻¹). Lean mass and resistin were preserved only in the DE group (P < 0.05). Fourteen days of CHO-reduced diet improved OGIS and fat oxidation (RER) in obese subjects. The energy-balanced HIIT did not further enhance these parameters, but increased aerobic capacity (VO_2peak) and preserved lean mass and resistin.     

Hyperglycaemia is responsible for the inhibited gastrointestinal transit in the early diabetic rat

The effect of plasma glucose levels on the gastrointestinal motility of the rat was studied. Chronic hyperglycaemia was induced by i. v. injection of streptozotocin 1 week before the motility experiment. Some rats received additional daily insulin therapy (1.25, 2.5 or 10 IU kg^-1) after induction of diabetes mellitus. Acute hyperglycaemia was induced by the continuous i. v. infusion of glucose solution (11, 22, 44 or 88 mg kg^-1 min^-1) 10 min before the motility experiments. The rats were killed 15 min after successful orogastric feeding of a charcoal-contained suspension. Gastrointestinal transit was calculated as the percentage of the overall lenght of the small intestine to which the charcoal moved during this time period. The diabetic rats were found to have delayed transit compared with controls (meanpLSEM: 32.2pL2.1% vs. 42.9pL4.2%, P<0.05). Correction with moderate doses of insulin therapy failed to inhibt transit, whereas hypoglycaemia induced by high-dose insulin treatment enhanced transit, whereas hypoglycaemia induced by high-dose insulin treatment enhanced transit. High doses of glucose elicited acute hyperglycaemia and delayed transit when compared with saline infused non-diabetic rats. In early diabetes, hyperglycaemia probably mediates the inhibited gastrointestinal transit, since correction of hyperglycaemia usually restores the delayed transit.     

Experimental type 2 diabetes induction reduces serum vaspin,but not serum omentin,in Wistar rats

Vaspin and omentin are adipose tissue adipokines that have often been related to obesity and its comorbidities. The aim of this study was to investigate the behaviour of serum omentin and vaspin in models of type 2 diabetes. To do this, Wistar rats (~200 g) were randomly divided into two groups: a non‐diabetic group (n = 6) and a diabetic group fed on a high‐fat diet (n = 6) and a low dose of streptozotocin (Sigma^®). All procedures were approved by the Brazilian Ethics Committee. Body weight (BW) and food intake were recorded daily. Tail blood glucose levels were assessed at the end of the diabetes induction period. The insulin tolerance test (ITT) was performed after the diabetes induction period (7 weeks). The serum and tissues (liver, pancreas, and retroperitoneal (RET), epididymal (EPI) and visceral (VIS) white adipose tissues) were immediately removed and weighed. Analyses of levels of insulin, omentin, vaspin, adiponectin and inflammatory cytokines IL‐6, IL‐8 (CXCL8), TNF‐α and C‐reactive protein (CRP) in serum were performed using the enzyme‐linked immunosorbent assay (ELISA). Our results showed that IL‐8 and CRP serum levels in the diabetic group were significantly higher than in the non‐diabetic group. Vaspin and adiponectin values were lower for the diabetic group than for the non‐diabetic group. Omentin, IL‐6 and TNF‐α values did not differ between the groups. Our results showed that both the metabolism of the adipose tissue and the secretion of adipokines may be affected in diabetic rats. Omentin showed no difference between the groups, although the vaspin values decreased in the diabetic group.     

Protective effects of bone marrow mononuclear cell therapy on lung and heart in an elastase-induced emphysema model

We hypothesized that bone marrow-derived mononuclear cell (BMDMC) therapy protects the lung and consequently the heart in experimental elastase-induced emphysema. Twenty-four female C57BL/6 mice were intratracheally instilled with saline (C group) or porcine pancreatic elastase (E group) once a week during 4 weeks. C and E groups were randomized into subgroups receiving saline (SAL) or male BMDMCs (2 × 10(6), CELL) intravenously 3h after the first saline or elastase instillation. Compared to E-SAL group, E-CELL mice showed, at 5 weeks: lower mean linear intercept, neutrophil infiltration, elastolysis, collagen fiber deposition in alveolar septa and pulmonary vessel wall, lung cell apoptosis, right ventricle wall thickness and area, higher endothelial growth factor and insulin-like growth factor mRNA expressions in lung tissue, and reduced platelet-derived growth factor, transforming growth factor-β, and caspase-3 expressions. In conclusion, BMDMC therapy was effective at modulating the inflammatory and remodeling processes in the present model of elastase-induced emphysema.