The modulatory effect of leptin on the overall insulin production in ex-vivo normal rat pancreas

2006 ◽  
Vol 84 (2) ◽  
pp. 157-162 ◽  
Author(s):  
N. Haddad ◽  
R. Howland ◽  
G. Baroody ◽  
C. Daher

Leptin has a modulator effect on glucose-stimulated insulin secretion. To define the influences of different glucose (4, 8, 12, and 16 mmol/L) and leptin (5, 10, 15, and 20 nmol/L) concentrations on total insulin release in ex vivo pancreatic preparations, a customized perfusion technique was used. Such a profile of concentration brought about an index for the combined effect of leptin and glucose on the production of insulin. Insulin output was measured by radioimmunoassay. Stimulated by glucose alone in the control group, insulin secretion confirmed a bi-phasic pattern. Addition of leptin in the experimental group suppressed insulin secretion compared with control. A U-shape pattern of suppression was observed when the leptin and stimulatory glucose concentrations were combined. At 12 mmol/L glucose, leptin showed maximal insulin suppression. Leptin’s effect on insulin was glucose dependent and showed a reproducible U-shaped pattern of suppression, which implicated possible direct dose-dependent interaction between leptin and glucose on insulin secretion.

2021 ◽  
Vol 2 (3) ◽  
pp. 100728
Author(s):  
Yun-Xia Zhu ◽  
Yun-Cai Zhou ◽  
Yan Zhang ◽  
Peng Sun ◽  
Xiao-Ai Chang ◽  
...  

2016 ◽  
Vol 18 (3(71)) ◽  
pp. 201-204
Author(s):  
S.V. Yurchak ◽  
O.V. Derenj ◽  
O.I. Vishchur ◽  
Yu.M. Zabytivskyi

The article consist data about effect of different levels of vitamin E and selenium in the diet of carps during their growing and also informationabout the influence on processes of lipid peroxidation and activity of antioxidant protection in their body.The experiment conducted in three experimental ponds. After wintering there were placed four ears mature females and males carp, six individuals in each group. Supplements of vitamin E administered at a rate of 25 mg/kg and drug «Sel–Plex» the rate of selenium – 0.3 mg/kg were added to further basic diet(BD) of female and male carp first experimental group (EG1). The second experimental group (EG2) received (BD) and vitamin E supplements in an amount of 75 mg / kg, and just as in EG1 – selenium – 0.3 mg/kg of feed.The control group received fish feed without additives vitamins and minerals.Feeding lasted for 30 days, due to the physiological needs of the fish feed. After spawning in fish of research and control group swere taken blood samples for biochemical research.The study led to a dose–dependent decrease (p < 0.01 – 0.001) content of TBA–active products and hydroperoxidase of lipids, but did not significantly effect onsuperoxide dismutase and glutathione peroxidase activity of blood So, the reduction of lipid peroxidation products in the carp’s blood of experimental groups probably was caused by the growth of non–enzymatic level, which is associated with fat–soluble vitamins. 


2003 ◽  
Vol 177 (2) ◽  
pp. 197-205 ◽  
Author(s):  
MJ Holness ◽  
ND Smith ◽  
GK Greenwood ◽  
MC Sugden

Abnormal depletion or accumulation of islet lipid may be important for the development of pancreatic beta cell failure. Long-term lipid sensing by beta cells may be co-ordinated via peroxisome proliferator-activated receptors (PPARs). We investigated whether PPARalpha activation in vivo for 24 h affects basal and glucose-stimulated insulin secretion in vivo after intravenous glucose administration and ex vivo in isolated perifused islets. Insulin secretion after intravenous glucose challenge was greatly increased by high-fat feeding (4 weeks) but glucose tolerance was minimally perturbed, demonstrating insulin hypersecretion compensated for insulin resistance. The effect of high-fat feeding to enhance glucose-stimulated insulin secretion was retained in perifused islets demonstrating a stable, long-term effect of high-fat feeding to potentiate islet glucose stimulus-secretion coupling. Treatment of high-fat-fed rats with WY14,643 for 24 h reversed insulin hypersecretion in vivo without impairing glucose tolerance, suggesting improved insulin action, and ex vivo in perfused islets. PPARalpha activation only affected hypersecretion of insulin since glucose-stimulated insulin secretion was unaffected by WY14,643 treatment in vivo in control rats or in perifused islets from control rats. Our data demonstrate that activation of PPARalpha for 24 h can oppose insulin hypersecretion elicited by high-fat feeding via stable long-term effects exerted on islet function. PPARalpha could, therefore, participate in ameliorating abnormal glucose homeostasis and hyperinsulinaemia in dietary insulin resistance via modulation of islet function, extending the established requirement for PPARalpha for normal islet lipid homeostasis.


Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 311 ◽  
Author(s):  
Sunmin Park ◽  
Ting Zhang ◽  
Jing Yi Qiu ◽  
Xuangao Wu ◽  
Jeong-Yong Lee ◽  
...  

Silk fibroin hydrolysates have been reported to reduce hyperglycemia, but the mechanism has not been determined in Asian type 2 diabetes (T2DM). We hypothesized that the consumption of acid hydrolyzed silk peptides (SPs) alleviates hyperglycemia by improving insulin sensitivity and subsequently normalizing glucose-stimulated insulin secretion in T2DM. We investigated this hypothesis in a partial pancreatectomized (Px) rat model. Px rats was assigned randomly to the following six groups and fed assigned diet for 8 weeks: the Px-control (0.5 g/kg/day dextrin), the SP-L (0.05 g/kg/day), the SP-M (0.1 g/kg/day), the SP-H (0.5 g/kg/day), the positive-control (40 mg/kg/day metformin), or the normal-control (sham-operated rats; 0.5 g/kg/day dextrin). SPs contained high levels of glycine, alanine, and serine. We found SPs dose-dependently increased food efficiency and body weight gain in Px rats. Animals in the Px-control group rats exhibited lower glucose metabolism, as evidenced by impaired glucose-stimulated insulin secretion coupled with impaired insulin sensitivity, and reduced bone mineral density (BMD) and lean body mass (LBM), compared to the normal-control. SPs and metformin similarly partially protected against Px-induced BMD loss in the lumbar spine and femur. Px-induced decreases in LBM were dose-dependently prevented by SPs, and muscle forces in the SP-M and SP-H groups were maintained at the normal-control level. Glucose tolerance was dose-dependently improved by SPs as determined by oral glucose tolerance and oral maltose tolerance tests, and glucose tolerances were similar in the SP-H and positive-control groups. Insulin tolerance, an index of insulin sensitivity, was dose-dependently enhanced by SPs, and the SP-H group exhibited better insulin tolerance than the positive-control group as determined by intraperitoneal insulin sensitivity testing. Insulin secretory capacity assessed using a hyperglycemic clamp improved in the following order: Px-control <SA-L <SA-M <positive-control <SA-H <normal-control. SP-M prevented gut microbiota dysbiosis. In conclusion, SPs administered at 0.1–0.5 g/kg/day improved glucose regulation by potentiating both insulin secretion and insulin sensitivity in non-obese T2DM rats.


2015 ◽  
Vol 118 (6) ◽  
pp. 692-698 ◽  
Author(s):  
Audrey Lee-Gosselin ◽  
David Gendron ◽  
Marie-Renée Blanchet ◽  
David Marsolais ◽  
Ynuk Bossé

Airway hyperresponsiveness to a spasmogenic challenge such as methacholine, and an increased baseline tone measured by the reversibility of airway obstruction with a bronchodilator, are two common features of asthma. However, whether the increased tone influences the degree of airway responsiveness to a spasmogen is unclear. Herein, we hypothesized that increased tone augments airway responsiveness in vivo by increasing the contractile capacity of airway smooth muscle (ASM). Anesthetized, tracheotomized, paralyzed, and mechanically ventilated mice were either exposed (experimental group) or not (control group) to tone for 20 min, which was elicited by nebulizing serial small doses of methacholine. Respiratory system resistance was monitored during this period and the peak response to a large cumulative dose of methacholine was then measured at the end of 20 min to assess and compare the level of airway responsiveness between groups. To confirm direct ASM involvement, the contractile capacity of excised murine tracheas was measured with and without preexposure to tone elicited by either methacholine or a thromboxane A2 mimetic (U46619). Distinct spasmogens were tested because the spasmogens liable for increased tone in asthma are likely to differ. The results indicate that preexposure to tone increases airway responsiveness in vivo by 126 ± 37% and increases the contractile capacity of excised tracheas ex vivo by 23 ± 4% for methacholine and 160 ± 63% for U46619. We conclude that an increased tone, regardless of whether it is elicited by a muscarinic agonist or a thromboxane A2 mimetic, may contribute to airway hyperresponsiveness by increasing the contractile capacity of ASM.


Author(s):  
Caitlin N Cadaret ◽  
Robert J Posont ◽  
Rebecca M Swanson ◽  
Joslyn K Beard ◽  
Rachel L Gibbs ◽  
...  

Abstract In humans and animals, intrauterine growth restriction (IUGR) results from fetal programming responses to poor intrauterine conditions. Chronic fetal hypoxemia elevates circulating catecholamines, which reduces skeletal muscle β2 adrenoceptor content and contributes to growth and metabolic pathologies in IUGR-born offspring. Our objective was to determine whether intermittent maternofetal oxygenation during late gestation would improve neonatal growth and glucose metabolism in IUGR-born lambs. Pregnant ewes were housed at 40°C from the 40 th to 95 th d of gestational age (dGA) to produce IUGR-born lambs (n = 9). A 2 nd group of IUGR-born lambs received prenatal O2 supplementation via maternal O2 insufflation (100% humidified O2, 10 L/min) for 8 h/d from dGA 130 to parturition (IUGR+O2, n = 10). Control lambs (n = 15) were from pair-fed thermoneutral ewes. All lambs were weaned at birth, hand-reared, and fitted with hindlimb catheters at d 25. Glucose-stimulated insulin secretion (GSIS) and hindlimb hyperinsulinemic-euglycemic clamp (HEC) studies were performed at d 28 and 29, respectively. At d 30, lambs were euthanized and ex vivo HEC studies were performed on isolated muscle. Without maternofetal oxygenation, IUGR lambs were 40% lighter (P &lt; 0.05) at birth and maintained slower (P &lt; 0.05) growth rates throughout the neonatal period compared to controls. At 30 d of age, IUGR lambs had lighter (P &lt; 0.05) hindlimbs and flexor digitorum superficialis (FDS) muscles. IUGR+O2 lambs exhibited improved (P &lt; 0.05) birthweight, neonatal growth, hindlimb mass, and FDS mass compared to IUGR lambs. Hindlimb insulin-stimulated glucose utilization and oxidation rates were reduced (P &lt; 0.05) in IUGR but not IUGR+O2 lambs. Ex vivo glucose oxidation rates were less (P &lt; 0.05) in muscle from IUGR but not IUGR+O2 lambs. Surprisingly, β2 adrenoceptor content and insulin responsiveness were reduced (P &lt; 0.05) in muscle from IUGR and IUGR+O2 lambs compared to controls. In addition, glucose-stimulated insulin secretion was reduced (P &lt; 0.05) in IUGR lambs and only modestly improved (P &lt; 0.05) in IUGR+O2. Insufflation of O2 also increased (P &lt; 0.05) acidosis and hypercapnia in dams, perhaps due to the use of 100% O2 rather than a gas mixture with a lesser O2 percentage. Nevertheless, these findings show that intermittent maternofetal oxygenation during late gestation improved postnatal growth and metabolic outcomes in IUGR lambs without improving muscle β2 adrenoceptor content.


Author(s):  
John Whitaker ◽  
Radhouene Neji ◽  
Nicholas Byrne ◽  
Esther Puyol-Antón ◽  
Rahul K. Mukherjee ◽  
...  

Abstract Background Ex-vivo cardiovascular magnetic resonance (CMR) imaging has played an important role in the validation of in-vivo CMR characterization of pathological processes. However, comparison between in-vivo and ex-vivo imaging remains challenging due to shape changes occurring between the two states, which may be non-uniform across the diseased heart. A novel two-step process to facilitate registration between ex-vivo and in-vivo CMR was developed and evaluated in a porcine model of chronic myocardial infarction (MI). Methods Seven weeks after ischemia-reperfusion MI, 12 swine underwent in-vivo CMR imaging with late gadolinium enhancement followed by ex-vivo CMR 1 week later. Five animals comprised the control group, in which ex-vivo imaging was undertaken without any support in the LV cavity, 7 animals comprised the experimental group, in which a two-step registration optimization process was undertaken. The first step involved a heart specific flexible 3D printed scaffold generated from in-vivo CMR, which was used to maintain left ventricular (LV) shape during ex-vivo imaging. In the second step, a non-rigid co-registration algorithm was applied to align in-vivo and ex-vivo data. Tissue dimension changes between in-vivo and ex-vivo imaging were compared between the experimental and control group. In the experimental group, tissue compartment volumes and thickness were compared between in-vivo and ex-vivo data before and after non-rigid registration. The effectiveness of the alignment was assessed quantitatively using the DICE similarity coefficient. Results LV cavity volume changed more in the control group (ratio of cavity volume between ex-vivo and in-vivo imaging in control and experimental group 0.14 vs 0.56, p < 0.0001) and there was a significantly greater change in the short axis dimensions in the control group (ratio of short axis dimensions in control and experimental group 0.38 vs 0.79, p < 0.001). In the experimental group, prior to non-rigid co-registration the LV cavity contracted isotropically in the ex-vivo condition by less than 20% in each dimension. There was a significant proportional change in tissue thickness in the healthy myocardium (change = 29 ± 21%), but not in dense scar (change = − 2 ± 2%, p = 0.034). Following the non-rigid co-registration step of the process, the DICE similarity coefficients for the myocardium, LV cavity and scar were 0.93 (±0.02), 0.89 (±0.01) and 0.77 (±0.07) respectively and the myocardial tissue and LV cavity volumes had a ratio of 1.03 and 1.00 respectively. Conclusions The pattern of the morphological changes seen between the in-vivo and the ex-vivo LV differs between scar and healthy myocardium. A 3D printed flexible scaffold based on the in-vivo shape of the LV cavity is an effective strategy to minimize morphological changes in the ex-vivo LV. The subsequent non-rigid registration step further improved the co-registration and local comparison between in-vivo and ex-vivo data.


2004 ◽  
Vol 107 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Wendy E. HEYWOOD ◽  
Nasi MIAN ◽  
Peter J. MILLA ◽  
Keith J. LINDLEY

Poor fetal and infant nutrition has been linked to impaired glucose tolerance in later life. We studied the effect of protein deficiency during gestation and the suckling period in a rat model and found that poor nutrition ‘programmes’ pancreatic β-cell GK (glucokinase; known as the glucose sensor) and glucose-stimulated insulin secretion response in newborn, suckling and adult rat offspring. Pregnant female rats were divided into three groups: a control group was kept on a normal protein (20%) diet, another group was fed a low-protein (LP) (6%) diet during gestation and suckling periods (LP-G + S group) and another was fed a LP diet during gestation then a normal protein diet during the suckling period (LP-G group). The pulsatile glucose-stimulated insulin secretion response was acutely disrupted and the peak insulin secretion was markedly decreased in newborn and 3-week-old offspring of the LP-G + S group compared with the control group. Also, there was an altered pulsatile secretory response in adults of the LP-G + S and 3-week-old and adult offspring of the LP-G groups compared with the control group. GK protein levels, detected by Western blotting, were decreased in newborn and 3-week-old offspring of both LP-G + S and LP-G groups compared with the control groups. The Km and Vmax of GK were altered. The prenatal and postnatal LP diet appeared to have a permanent effect in increasing the affinity of GK for glucose (indicated by decreased Km values) and decreasing the Vmax. This showed that the critical period of programming of the function of GK was after birth and during the postnatal weaning period, since the adult offspring of the LP-G + S group when fed a normal protein diet showed no reversal in the Km values of the enzyme. Similar experiments in adult offspring of the LP-G group showed normalization of the Km values of GK at 3 weeks of age. In conclusion, fetal and infantile nutrition ‘programmes’ pancreatic β-cell function; poor nutrition during this period caused irreversible effects on glucose homoeostatic mechanisms in the offspring, which may predispose the offspring to diabetes in later life.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Barbara Šenk ◽  
Katja Goričar ◽  
Nika Aleksandra Kravos ◽  
Mojca Jensterle Sever ◽  
Andrej Janež ◽  
...  

Purpose. To investigate in a pilot study of genetic polymorphisms in serotonin system influencing basal- and glucose-stimulated insulin secretion in women with polycystic ovary syndrome (PCOS). Methods. A cross-sectional study included 65 female patients with PCOS followed up at the endocrine outpatient clinic of the University Medical Center Ljubljana and a control group of 94 young healthy female blood donors. Oral glucose tolerance test was performed only in PCOS patients and basal- and glucose-stimulated blood glucose and insulin levels were measured. All the subjects were genotyped for 5HTR1A rs6295, 5HTR1B rs13212041, and SLC6A4 5HTTLPR polymorphisms in the serotonin system. Results. Genotype distributions were in accordance with the Hardy-Weinberg equilibrium (HWE), except for 5HTR1A rs6295 in healthy controls and 5HTR1B rs13212041 in PCOS patients that were not consistent with HWE. SLC6A4 5HTTLPR polymorphism was significantly associated with insulin secretion (p=0.030) and with the area under the curve of insulin blood levels during OGTT (p=0.021). None of the investigated polymorphisms was significantly associated with basal- or glucose-stimulated blood glucose levels at any point in time during OGTT or with the basal insulin concentration. Conclusions. Serotonin system may play a role in glucose-stimulated insulin secretion in patients with insulin resistance (IR) and decreased insulin sensitivity. Further studies are needed to conclude whether the observed effect is characteristic for PCOS-related metabolic disturbances or for the identified mutation in different high metabolic risk populations.


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