Protective Effect of Insulin in Mouse Nasal Mucus Against Olfactory Epithelium Injury

Insulin is present in nasal mucus and plays an important role in the survival and activity of individual olfactory sensory neurons (OSNs) via insulin receptor-mediated signaling. However, it is unclear whether insulin acts prophylactically against olfactotoxic drug-induced olfactory epithelium (OE) injury, and whether the degree of damage is affected by the concentration of insulin in the nasal mucus. The apoptosis-inducing drug methimazole was administered to the nasal mucus of diabetic and normal mice along with different concentrations of insulin. Immunohistochemical analysis was used to assess the relationship between damage to the OE and the mucus insulin concentration and the protective effect of insulin administration against eosinophilic cationic protein (ECP)-induced OE injury. Diabetic mice had lower concentrations of insulin in their nasal mucus than normal mice (diabetic vs. normal mice, p < 0.001). Methimazole administration reduced the number of OSNs in normal mice and had a more marked effect in diabetic mice. However, unilateral insulin administration prevented the methimazole-induced reduction in the number of OSNs on the ipsilateral side but not on the contralateral side (OSNs; Insulin vs. contralateral side, p < 0.001). Furthermore, intranasal ECP administration damaged the OE by inducing apoptosis (OSNs; ECP vs. contralateral side, p < 0.001), but this damage was largely prevented by insulin administration (OSNs; Insulin + ECP vs. contralateral side, p = 0.36), which maintained the number of mature OSNs. The severity of methimazole-induced damage to the OE is related to the insulin concentration in the nasal mucus (Correlation between the insulin concentration in nasal mucus and the numbers of OSNs, R2 = 0.91, p < 0.001), which may imply that nasal insulin protects OSNs and that insulin administration might lead to the development of new therapeutic agents for ECP-induced OE injury.

Antioxidant capacity, reproductive response and glucose concentration and insulin of ewes supplemented prior to insemination with orange residue

ABSTRACT The objective was to evaluate the antioxidant capacity, glucose and insulin concentration and reproductive performance of ewes supplemented with orange residue prior to insemination. Fifty-five multiparous ewes were divided into two corrals, and 15 unbred ewes were kept individually to measure feed consumption. Two integral diets were administered; T0: control treatment and T1: with 20% of dry matter of orange residue. Ten days after the start of supplementation, the ewes were synchronized. Supplementation was finalized prior to artificial insemination, then, a blood sample was taken to measure the antioxidant capacity and glucose and insulin concentration. An analysis of variance was made to evaluate the effect of treatment on the antioxidant capacity, glucose and insulin; and to analyze the response to estrus, percentage of gestation and prolificity a ji squared test was performed. Of 9 antioxidant compounds found in the orange residue, hesperidin (7.44%), chlorogenic acid (0.50%) and protocatechuic acid had the highest concentration. Feed intake, estrus response, percentage of gestation, antioxidant capacity, and glucose and insulin concentration were not affected by the treatment. It is concluded that inclusion of 20% of orange residue in the diet prior to insemination in ewes is possible.

Ficus thonningii Stem Bark Extracts Prevent High Fructose Diet Induced Increased Plasma Triglyceride Concentration, Hepatic Steatosis and Inflammation in Growing Sprague-Dawley Rats

BACKGROUND: Ficus thonningii extracts exhibit hypoglycaemic, hypolipidaemic and antioxidant activities. We investigated the potential of methanolic F. thonningii stem-bark extracts (MEFT) to protect growing Sprague-Dawley (SD) against high-fructose diet-induced metabolic derangements (MD) in a model mimicking children fed obesogenic diets. METHODS: Eighty (40 males; 40 females) 21-days old SD rat pups were randomly allocat-ed to and administered, for 8 weeks, five treatment regimens: 1 - standard rat chow (SC) + water (PW), 2 - SC + 20% (w/v) fructose solution (FS), 3 - SC + FS + fenofibrate at 100 mg/kg bwt/day, 4 - SC + FS + low dose MEFT (LD; 50 mg/kg bwt/day) and 5 - SC + FS + high dose MEFT (HD; 500 mg/kg bwt/day). Body weight, glucose load tolerance, fasting blood glucose and triglyceride, plasma insulin concentration, sensitivity to insulin, liver mass and fat content, steatosis and inflammation were determined. RESULTS: Fructose had no effect on the rats’ growth, glucose and insulin concentration, glucose tolerance and insulin sensitivity (P>0.05) but increased triglycerides in females; in-duced hepatic microsteatosis and inflammation in both sexes but macrosteatosis in females (P<0.05). In females, MEFT prevented fructose-induced plasma triglyceride increase. Low dose MEFT increased liver lipid content in females (P<0.05). The MEFT protected the rats against hepatic steatosis and inflammation but fenofibrate protected against hepatic mi-crosteatosis. CONCLUSION: MEFT can be used as prophylaxis against dietary fructose-induced ele-ments of MD but caution must be taken as low dose MEFT increases hepatic lipid accretion in females predisposing to fatty liver disease.

An algorithm mimicking pancreas pulsatile behavior improves artificial pancreas performance

Background: Artificial pancreas design using subcutaneous insulin infusion without pre-meal feed-forward boluses often induces an over-response leading to hypoglycemia due to the increase of blood insulin concentration sustained in time. The objective of this work was to create an algorithm for controlling the function of insulin pumps in closed-loop systems to improve blood glucose management in type 1 diabetic patients by mimicking the pulsatile behaviour of the pancreas. Methods: A controller tuned in a pulsatile way promotes damped oscillations of blood insulin concentration injected through an insulin pump. We tested it in a simulated environment, using nine ‘in silica’ subjects. The control algorithm is founded on feedback linearization where through a change of variables, the nonlinear system turns into an equivalent linear system, suitable for implementing through a PID controller. We compared the results obtained ‘in silica’ with the volume injected by an insulin pump controlled by this algorithm. Results: The use of this algorithm resulted in a pulsatile control of postprandial blood glucose concentration, avoiding hypoglycaemic episodes. The results obtained ‘in silica’ were replicated in a real pump ‘in vitro’. Conclusions: With this proposed linear system, an appropriate control input can be designed. The controller works with a damped pulsatile pattern making the insulin infusion from the pump and blood insulin concentration pulsatile. This operational would improve the performance of an artificial pancreas.

Effects of Dietary Calcium Propionate Supplementation on Hypothalamic Neuropeptide Messenger RNA Expression and Growth Performance in Finishing Rambouillet Lambs

The objective of this experiment was to evaluate the effects of feeding different levels concentrations of dietary calcium propionate (CaPr) on lambs’ growth performance; ruminal fermentation parameters; glucose–insulin concentration; and hypothalamic mRNA expression for neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC). Thirty-two individually fed lambs were randomly assigned to four treatments: (1) control diet (0 g/kg of CaPr), (2) low CaPr, (30 g/kg dry matter (DM)), (3) medium CaPr, (35 g/kg DM), and (4) high CaPr (40 g/kg DM). After 42 days of feeding, lambs were slaughtered for collecting samples of the hypothalamus. Data were analyzed as a complete randomized design, and means were separated using linear and quadratic polynomial contrast. Growth performance was not affected (p ≥ 0.11) by dietary CaPr inclusion. The ruminal concentration of total volatile fatty acids (VFA) increased linearly (p = 0.04) as dietary CaPr increased. Likewise, a linear increase in plasma insulin concentration (p = 0.03) as dietary CaPr concentration increased. The relative mRNA expression of NPY exhibited a quadratic effect (p < 0.01), but there were significant differences in the mRNA expression of AgRP and POMC (p ≥ 0.10). Dietary calcium propionate did not improve lamb growth performance in lambs feed with only forage diets. Intake was not correlated with feed intake with mRNA expression of neuropeptides.

EFECT OF INTENSIVE PHYSICAL LOADS ON TESTOSTERONE, CORTISOL AND INSULIN BLOOD CONCENTRATIONS IN ELITE ATHLETES

The aim of the work was to investigate the effect of intense physical activity on testosterone, cortisol and insulin blood concentration in elite athletes. The study was conducted with the participation of 26 elite athletes of endurance events. This study assessed the resting hormones concentration before exercise and acute response of hormones concentration after intensive physical loads. The influence of intensive physical loads with different direction (strength and speed vs incremental load to VO2 max achievement) was investigated. The average values of total testosterone in blood serum, measured at rest state before exercise were 28,2 nmol·l-1, 40 minutes after exercise – 19,2 nmol·l-1. The mean concentration of cortisol was 506,2 nmol·l-1, after physical activity – 518,1 nmol·l-1. The average value morning insulin concentration was 6,6 μIU·l-1, after loading 5,6 μIU·l-1. It was established a significant (p = 0.001) decrease of the total testosterone concentration after intensive physical loads; the registered changes in the blood cortisol and insulin concentrations were not statistically significant. A significant correlation was established (p ≤ 0.05) between the maximum oxygen consumption (VO2max, ml·min·kg-1) and testosterone concentration (r = 0.76 resting morning concentration, r = 0.87 after intensive physical loads), cortisol (r = 0.69) and insulin (r = 0.51) after exercising. It was established the differences in testosterone concentration due intensive physical loads with various direction (strength and speed vs incremental load to VO2 max achievement). The significant difference of cortisol and insulin concentration depending the physical test was not found in this study.