Abstract:
:Plasticity of insulin secretion is essential to maintain the action of insulin during insulin resistance and to prevent diabetes. Investigation of the plasticity of insulin secretion and its regulation is challenging, and the objective of this study was to develop a novel large-animal-based model. The effect of chronic moderate hyperglycaemia on the plasticity of insulin secretion, β-cell mass and function was determined in sheep. Adolescent sheep (120 days old) were infused with 25% glucose for 16 days to increase blood glucose by 50% (n = 10), and control animals (n = 9) were infused with saline. Glucose- and arginine-stimulated insulin secretion, insulin sensitivity and glucose effectiveness were measured in vivo before and during treatment (days 10-14), and β-cell mass was measured at the end of treatment. Hyperglycaemia increased blood glucose (+53%) and plasma insulin (+403%; each P < 0.003) and did not alter whole-body insulin sensitivity. Hyperglycaemia increased glucose-stimulated insulin secretion (particularly second phase; five-fold) and arginine-stimulated insulin secretion (particularly first phase; four-fold). Hyperglycaemia reduced β-cell mass (∼50%, P = 0.038) and increased glucose- and arginine-stimulated insulin secretion relative to β-cell mass five-fold (P = 0.060) and 20-fold (P = 0.007), respectively. Chronic hyperglycaemia therefore induces marked adaptation and upregulation of glucose- and arginine-stimulated insulin secretion by enhancing β-cell function rather than increasing β-cell mass in the sheep, consistent with long-term adaptations seen in humans. This marked plasticity of insulin secretion in response to moderate hyperglycaemia provides a novel model for the investigation of factors affecting its capacity and underlying determinants.
journal_name
Exp Physioljournal_title
Experimental physiologyauthors
Gatford KL,De Blasio MJ,How TA,Harland ML,Summers-Pearce BL,Owens JAdoi
10.1113/expphysiol.2011.063560subject
Has Abstractpub_date
2012-05-01 00:00:00pages
663-75issue
5eissn
0958-0670issn
1469-445Xpii
expphysiol.2011.063560journal_volume
97pub_type
杂志文章abstract::Neural activation decreases cerebral deoxyhaemoglobin (HHb(C)) and increases oxyhaemoglobin concentration (O(2)Hb(C)). In contrast, patients who present with restricted cerebral blood flow, such as those suffering from cerebral ischaemia or Alzheimer's disease, and during the course of ageing the converse occurs, in t...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/expphysiol.2011.061978
更新日期:2012-02-01 00:00:00
abstract:NEW FINDINGS:What is the central question of this study? Does treatment of obstructive sleep apnoea (OSA) with nocturnal oxygen or continuous positive airway pressure (CPAP) improve hypoxic vascular responses, which are reportedly impaired in OSA? What is the main finding and its importance? Cerebrovascular and cardiov...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/EP086845
更新日期:2019-04-01 00:00:00
abstract::It is unclear whether cardiac hypertrophy and hypertrophy-related pathways will be induced by long-term intermittent hypoxia. Thirty-six Sprague-Dawley rats were randomly assigned into three groups: normoxia, and long-term intermittent hypoxia (12% O(2), 8 h per day) for 4 weeks (4WLTIH) or for 8 weeks (8WLTIH). Myoca...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/expphysiol.2006.036590
更新日期:2007-03-01 00:00:00
abstract::Latex beads coated with secretory immunoglobulin (IgA) instilled into mouse intestinal loops are taken up by M cells present in Peyer's patch follicle-associated epithelial tissue. Bead adsorption and uptake is greater at the edge compared with the apex of follicle domes. Coating beads with bovine serum albumin (BSA) ...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/expphysiol.1992.sp003662
更新日期:1992-11-01 00:00:00
abstract::Beneficial effects of exercise training on the vasculature have been consistently reported in subjects with cardiovascular risk factors or disease, whereas studies in apparently healthy subjects have been less uniform. In this review, we examine evidence pertaining to the impact of exercise training on conduit and res...
journal_title:Experimental physiology
pub_type: 杂志文章,评审
doi:10.1113/expphysiol.2009.048694
更新日期:2011-02-01 00:00:00
abstract::A considerable body of evidence indicates that the intracellular chloride concentration ([Cl-]i) is an important regulatory signal in epithelial ion transport. [Cl-]i regulates the open channel probability of sodium and chloride channels, the rate of chloride channel recycling to the apical membrane, cell volume homeo...
journal_title:Experimental physiology
pub_type: 杂志文章,评审
doi:10.1113/expphysiol.2005.031823
更新日期:2006-01-01 00:00:00
abstract::The results of this investigation demonstrate, using a position matching paradigm, that the ability of subjects to detect changes in the position of the proximal interphalangeal joint is impaired in patients with rheumatoid arthritis affecting this joint. In this group there is a systematic flexion bias in position ju...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/expphysiol.1992.sp003633
更新日期:1992-09-01 00:00:00
abstract::The present study was designed to analyse the effects of aerobic exercise on the metabolic effects of alloxan. Male Wistar newborn rats (2 days old) received alloxan (200 mg (kg body weight)(-1)) intraperitoneally (A rats). Vehicle-injected rats were used as controls (C rats). At 28 days old, some of the A rats were s...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/expphysiol.2004.028241
更新日期:2005-01-01 00:00:00
abstract::Rats were fed a liquid diet with the aim of decreasing nervous reflex activity in the parotid glands. In rats killed after 21 days on this diet the glands were atrophied and the total amounts of the neuropeptides, substance P, vasoactive intestinal peptide and calcitonin gene-related peptide, were lower than in contro...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/expphysiol.1990.sp003435
更新日期:1990-07-01 00:00:00
abstract::It is debatable whether differences in mitochondrial function exist across skeletal muscle types and whether mouse skeletal muscle mitochondrial function can serve as a valid model for human skeletal muscle mitochondrial function. The aims of this study were to compare and contrast three different mouse skeletal muscl...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/expphysiol.2012.070037
更新日期:2013-04-01 00:00:00
abstract:NEW FINDINGS:What is the central question of this study? Can low-dose inorganic nitrate supplementation prevent testicular structural and functional alterations in streptozotocin-induced type 1 diabetic male rats? What is the main finding and it's important? Treatment with a low dose of inorganic nitrate for 2 months h...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/EP087198
更新日期:2018-12-01 00:00:00
abstract::It is commonly stated that smell elicits a parotid salivary reflex in humans. However, this assumption seems to be supported only by experiments in which either a lemon or an irritating odour has been used as the primary stimulus. In this study six pleasant odours, chocolate, vanilla, peppermint, beef, tomato and lemo...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/expphysiol.1991.sp003502
更新日期:1991-05-01 00:00:00
abstract:NEW FINDINGS:What is the topic of this review? The manuscript collectively combines the experimental observations from >100 publications focusing on the regulation of cerebral blood flow and metabolism during exercise from 1945 to the present day. What advances does it highlight? This article highlights the importance ...
journal_title:Experimental physiology
pub_type: 杂志文章,评审
doi:10.1113/EP086249
更新日期:2017-11-01 00:00:00
abstract::This review explores the current concepts relating the structural and functional modifications of skeletal muscle mitochondria to the molecular mechanisms activated when organisms are exposed to a hypoxic environment. In contrast to earlier assumptions it is now established that permanent or long-term exposure to seve...
journal_title:Experimental physiology
pub_type: 杂志文章,评审
doi:10.1113/eph8802513
更新日期:2003-01-01 00:00:00
abstract::The present investigation was designed to examine whether calmodulin is involved in the inhibition of the ATP-sensitive K+ (K(ATP)) channel by glucagon-like peptide 1(7-36) amide (GLP-1) in mouse pancreatic beta-cells. Membrane potential, single channel and whole-cell currents through the K(ATP) channels, and intracel...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/eph8602173
更新日期:2001-05-01 00:00:00
abstract::We have demonstrated that the fluorescent microsphere technique can be used in small mammals for accurate determination of regional blood flows. In particular we have shown that 100% recovery of trapped microspheres is possible, that tissue digestion can be completed in a shorter time than previously reported, and the...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::This study examined the effect of pre-exercise carbohydrate (CHO) ingestion on pyruvate dehydrogenase complex (PDC) activation, acetyl group availability and substrate level phosphorylation (glycogenolysis and phosphocreatine (PCr) hydrolysis) in human skeletal muscle during the transition from rest to steady-state ex...
journal_title:Experimental physiology
pub_type: 临床试验,杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract::Previously, we undertook simultaneous recording of ventilation and pulmonary gas exchange in mice and revealed that dopamine D(2) receptors participate in exercise hyperpnoea via behavioural control of ventilation with unchanged pulmonary gas exchange. Here, we examined the hypothesis that D(1) receptors also contribu...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/expphysiol.2012.068312
更新日期:2013-02-01 00:00:00
abstract::The effects of two different feeding regimes on the 24 h profiles of maternal and fetal plasma cortisol and adrenocorticotrophic hormone (ACTH) concentrations were studied in eight pregnant ewes between 123 and 144 days of gestation. Once daily-fed ewes (n = 4) received 1 kg of lucerne-chaff at 11.00 h, and multi-fed ...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/expphysiol.1991.sp003488
更新日期:1991-03-01 00:00:00
abstract:NEW FINDINGS:What is the central question of this study? Does baroreceptor unloading during passive hyperthermia contribute to increases in ventilation and decreases in end-tidal carbon dioxide during that exposure? What is the main finding and its importance? Hyperthermic hyperventilation is not mitigated by expanding...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/EP085259
更新日期:2015-11-01 00:00:00
abstract:NEW FINDINGS:What is the central question of this study? What are the cellular and molecular determinants of increased risk for cardiovascular disease from prolonged sitting? What is the main finding and its importance? Prolonged sitting, independent of calf raise interruption strategies, decreases microparticle counts...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/EP088690
更新日期:2020-08-01 00:00:00
abstract::We hypothesized that exercise performance is adjusted during repeated sprints in order not to surpass a critical threshold of peripheral fatigue. Twelve men randomly performed three experimental sessions on different days, i.e. one single 10 s all-out sprint and two trials of 10 × 10 s all-out sprints with 30 s of pas...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/expphysiol.2014.077974
更新日期:2014-07-01 00:00:00
abstract::The autonomic adjustments to exercise are mediated by central signals from the higher brain (central command) and by a peripheral reflex arising from working skeletal muscle (exercise pressor reflex), with further modulation provided by the arterial baroreflex. Although it is clear that central command, the exercise p...
journal_title:Experimental physiology
pub_type: 杂志文章,评审
doi:10.1113/expphysiol.2005.032037
更新日期:2006-01-01 00:00:00
abstract:NEW FINDINGS:What is the central question of this study? Research has reported that some sensory input, such as auditory and olfactory input, can affect subliminal visual processing. However, it is important to address whether tactile input, another form of elementary sensory input, could influence the interocular riva...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/EP087944
更新日期:2019-11-01 00:00:00
abstract::The effects of hypotonic solutions on intracellular Ca2+ were determined on primary cultures of human detrusor smooth muscle cells. In the presence of external Ca2+, changing from a solution containing 290 mosmol l-1 to one containing 240 mosmol l-1 (80% normal tonicity) activated a rise in intracellular Ca2+. If the ...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/expphysiol.1997.sp004056
更新日期:1997-07-01 00:00:00
abstract::The uptake and distribution of CO throughout the circulatory system during two different methods of CO rebreathing (2 min 'Schmidt' and 40 min 'Burge' methods) were determined in nine healthy volunteers. Specifically, the impact of (i) differences in circulatory mixing time (t(mix)), (ii) CO diffusion to myoglobin (Mb...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/expphysiol.2010.054031
更新日期:2010-12-01 00:00:00
abstract::Altering [K+]o might have different effects on action potential duration (APD) in myocytes from different regions. Therefore, the effects of [K+]o on regional differences in action potential characteristics were investigated in sub-endocardial, mid-myocardial and sub-epicardial myocytes isolated from the base of guine...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1111/j.1469-445x.2000.02048.x
更新日期:2000-11-01 00:00:00
abstract::Exercise performance in hypoxia may be limited by a critical reduction in cerebral and skeletal tissue oxygenation, although the underlying mechanisms remain unclear. We examined whether increased systemic free radical accumulation during hypoxia would be associated with elevated microvascular deoxygenation and reduce...
journal_title:Experimental physiology
pub_type: 杂志文章,随机对照试验
doi:10.1113/expphysiol.2014.081265
更新日期:2014-12-01 00:00:00
abstract:NEW FINDINGS:What is the central question of this study? What mechanisms account for the hypotension observed during chronic elevations in circulating 5-hydroxytryptamine in rats? What is the main finding and its importance? Chronic 5-hydroxytryptamine-induced hypotension requires continued activation of the 5-HT7 rece...
journal_title:Experimental physiology
pub_type: 杂志文章
doi:10.1113/EP088919
更新日期:2020-10-14 00:00:00
abstract:NEW FINDINGS:What is the central question of this study? Does the magnitude of neuromuscular fatigue depend on the amount of work done (W') at task failure when cycling above critical power (CP)? What is the main finding and its importance? Creatine supplementation increases W' and enhances supra-CP performance, but in...
journal_title:Experimental physiology
pub_type: 杂志文章,随机对照试验
doi:10.1113/EP087886
更新日期:2019-12-01 00:00:00