Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “HOMEOSTASIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed2006

Dynamin is involved in endolysosomal cholesterol delivery to the endoplasmic reticulum: role in cholesterol homeostasis.

Cholesterol is one of the most essential membrane components in mammalian cells and plays a critical role in several cellular functions. It is now established that intracellular cholesterol transport contributes to the regulation of cellular cholesterol homeostasis by mechanisms that are yet poorly defined. In this study, we examined the role of clathrin- and dynamin-dependent trafficking on the regulatory machinery involved in cholesterol homeostasis. Thus, expression levels of three major sterol-sensitive genes, that is sterol-regulatory element binding protein 2 (SREBP-2), hydroxymethylglutaryl-coenzyme A (HMGCoA) reductase and low-density lipoprotein (LDL) receptor, were monitored to study the cell response to the addition of LDL-derived cholesterol. We found that inhibition of clathrin-dependent endocytosis had no effect on the intracellular distribution of cholesterol and the regulation of sterol-sensitive genes. In contrast, inhibition of dynamin activity resulted in the lack of regulation of SREBP-2, HMGCoA reductase and LDL receptor genes. Immunolocalization studies along with the measure of free and esterified cholesterol indicated that dynamin inactivation led to the accumulation of free cholesterol (FC) within the late endosomal (LE)/lysosomal compartment resulting in insufficient delivery of regulatory cholesterol to the endoplasmic reticulum (ER) where the transcriptional control of sterol-sensitive genes occurs. Our data therefore indicate that dynamin plays a critical role in the delivery of cholesterol from the LE/lysosomal network to the ER and highlight the importance of LE trafficking in cholesterol homeostasis.

Biological Transport↗
PubMed1989

Changes in calcium homeostasis during aging and Alzheimer's disease.

Several observations indirectly suggest that intracellular calcium regulation may be altered by aging and Alzheimer's disease. Thus, calcium homeostasis was examined directly in skin fibroblasts from Alzheimer's patients and compared to cells from normal young and elderly controls. Alterations in both bound and free calcium were noted; cells from Alzheimer's donors have higher levels of bound calcium but lower concentrations of free intracellular calcium when compared to cells from young and normal aged donors. These changes in calcium homeostasis may be physiologically significant, since processes that require transient elevations of intracellular free calcium, such as cell spreading, decline in the Alzheimer's cells. In summary, cultured skin fibroblasts from normal aged and Alzheimer's patients demonstrate deficits in calcium homeostasis and other metabolic processes when compared to cells from young donors.

Aging↗
PubMed2004

A definition of internal constancy and homeostasis in the context of non-equilibrium thermodynamics.

The constancy of the internal environment, internal homeostasis, and its stability are necessary conditions for the survival of a biological system within its environment. These have never been clearly defined. For this purpose nonequilibrium thermodynamics is taken as a reference, and the essential principles of equilibrium, reversibility, stationary steady state and stability (Lyapounov, asymptotic, local and global), are briefly illustrated. On this basis, internal homeostasis describes a stationary state of nonequilibrium, the actual state of rest, X(t), resulting from the relation X(t) = Xs + x(t), between a time-independent steady state of reference (Xs), and time-dependent fluctuations of the state variables, x(t). In humans, two resting spontaneous homeostatic states are: (1) the conscious state of quiet wakefulness, during which time-dependent variables display bounded oscillations around the mean time-independent steady state level, this conscious state being thus stable in the sense of Lyapounov, and (2) the unconscious stable state of non-rapid eye movement sleep, in which the time-dependent variables would approach the lowest spontaneously attainable time-independent state asymptotically, sleep becoming a globally stable and attractive state. Exercise may be described as a non-resting, unstable active state far away from equilibrium and hibernation is a resting, time-independent steady state very near equilibrium. The range between sleep and exercise is neurohumorally regulated. For spontaneously stable states to occur, slowing of the metabolic rate, withdrawal of the sympathetic drive and reinforcement of the vagal tone to the heart and circulation are required, thus confirming that the parasympathetic division of the autonomic nervous system is the main controller of homeostasis.

Homeostasis↗
PubMed2004

Effects of heat shock protein 70 activation by metabolic inhibition preconditioning or kappa-opioid receptor stimulation on Ca2+ homeostasis in rat ventricular myocytes subjected to ischemic insults.

Heat shock protein 70 (HSP70) mediates delayed cardioprotection of preconditioning. Cytosolic calcium ([Ca(2+)])(i) overload precipitates injury, whereas attenuation of [Ca(2+)](i) overload is believed to be responsible for cardioprotection. There is evidence suggesting a link between HSP70 and [Ca(2+)](i) homeostasis. We hypothesize that activation of HSP70 by preconditioning may restore [Ca(2+)](i) homeostasis altered by ischemic insults. To test the hypothesis, we determined the effects of preconditioning with metabolic inhibition or pretreating with U50,488H [trans-(+)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide (a kappa-opioid receptor agonist)] on viability and injury, HSP70 expression, and [Ca(2+)](i) in ventricular myocytes subjected to metabolic inhibition and anoxia (MI/A), with blockade of HSP70 synthesis. In myocytes with vehicle pretreatment, the percentage of dead cells determined by trypan blue exclusion, the injury reflected by release of lactate dehydrogenase, and the resting [Ca(2+)](i) measured by spectrofluorometry significantly increased, whereas the amplitude of electrically induced [Ca(2+)](i) transient decreased, after 10 min with 10 mM 2-deoxy-d-glucose and 10 mM sodium dithionite, known to cause MI/A. However, when myocytes were subjected for 30 min to either 20 mM lactate and 10 mM 2-deoxy-d-glucose (MIP) or 30 microM U50,488H (UP) 20 h before MI/A, the changes in viability and injury, and [Ca(2+)](i) responses were significantly attenuated. These were accompanied by a significantly increased HSP70 expression. Furthermore, blockade of HSP70 synthesis with selective antisense oligonucleotides abolished the beneficial effects of MIP or UP. This study provides first evidence that activation of HSP70 induced by preconditioning, which conferred delayed cardioprotection, restored partially the [Ca(2+)](i) homeostasis altered by ischemic insults.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2004

TRPM7: channeling the future of cellular magnesium homeostasis?

A recent paper by Schmitz and colleagues provides persuasive evidence that the ion channel transient receptor potential melastatin 7 (TRPM7) may be the long-sought regulator of magnesium (Mg) homeostasis in mammalian cells. This finding is not unexpected, because TRPM channels contain a kinase domain that allows them to participate in signal transduction pathways and regulatory networks. However, these studies introduce an exciting new twist into our understanding of Mg homeostasis; TRPM7 facilitates Mg entry into the cell, whereas other putative Mg transporters apparently operate in the opposite direction. By combining electrophysiological, biochemical, and genetic approaches, Schmitz and colleagues characterized most of the key features that demonstrate a well-defined and biologically plausible regulator of Mg homeostasis. TRPM7 genetics are well in hand, its regulation by intracellular free Mg2+ unravels the mechanisms of regulatory feedback loops, and its kinase domain modulates its sensitivity to free Mg2+. These findings are discussed in light of the indirect and descriptive information we had about Mg regulation before this rigorous characterization of TRPM7 brought it to the center of the Mg stage. Although the molecular events downstream of TRPM7 phosphorylation and dephosphorylation await in-depth elucidation, these results open up exciting perspectives in Mg research and may provide a much-needed tool with which to reexamine the role of Mg in cell proliferation and other important pathophysiologic events. Likewise, these findings will offer guidelines for research on disease states that are characterized by Mg imbalance.

Animals↗
PubMed1991

Inducible pH homeostasis and the acid tolerance response of Salmonella typhimurium.

The acid tolerance response (ATR) is an adaptive system triggered at external pH (pHo) values of 5.5 to 6.0 that will protect cells from more severe acid stress (J. Foster and H. Hall, J. Bacteriol. 172:771-778, 1990). Correlations between the internal pH (pHi) of adapted versus unadapted cells at pHo of 3.3 indicate that the ATR system produces an inducible pH-homeostatic function. This function serves to maintain the pHi above 5 to 5.5. Below this range, cells rapidly lose viability. Development of this pH homeostasis mechanism was sensitive to protein synthesis inhibitors and operated only to augment the pHi at pHo values below 4. In contrast, classical constitutive pH homeostasis was insensitive to protein synthesis inhibitors and was efficient only at pHo values above 4. Physiological studies indicated an important role for the Mg(2+)-dependent proton-translocating ATPase in affording ATR-associated survival during exposure to severe acid challenges. Along with being acid intolerant, cells deficient in this ATPase did not exhibit inducible pH homeostasis. We speculate that adaptive acid tolerance is important to Salmonella species in surviving acid encounters in both the environment and the infected host.

Acids↗
PubMed2000

The yeast model for batten disease: mutations in BTN1, BTN2, and HSP30 alter pH homeostasis.

The BTN1 gene product of the yeast Saccharomyces cerevisiae is 39% identical and 59% similar to human CLN3, which is associated with the neurodegenerative disorder Batten disease. Furthermore, btn1-Delta strains have an elevated activity of the plasma membrane H(+)-ATPase due to an abnormally high vacuolar acidity during the early phase of growth. Previously, DNA microarray analysis revealed that btn1-Delta strains compensate for the altered plasma membrane H(+)-ATPase activity and vacuolar pH by elevating the expression of the two genes HSP30 and BTN2. We now show that deletion of either HSP30 or BTN2 in either BTN1(+) or btn1-Delta strains does not alter vacuolar pH but does lead to an increased activity of the vacuolar H(+)-ATPase. Deletion of BTN1, BTN2, or HSP30 does not alter cytosolic pH but diminishes pH buffering capacity and causes poor growth at low pH in a medium containing sorbic acid, a condition known to result in disturbed intracellular pH homeostasis. Btn2p was localized to the cytosol, suggesting a role in mediating pH homeostasis between the vacuole and plasma membrane H(+)-ATPase. Increased expression of HSP30 and BTN2 in btn1-Delta strains and diminished growth of btn1-Delta, hsp30-Delta, and btn2-Delta strains at low pH reinforce our view that altered pH homeostasis is the underlying cause of Batten disease.

Culture Media↗
PubMed2005

Abnormal glucose homeostasis and pancreatic islet function in mice with inactivation of the Fem1b gene.

Type 2 diabetes mellitus is a disorder of glucose homeostasis involving complex gene and environmental interactions that are incompletely understood. Mammalian homologs of nematode sex determination genes have recently been implicated in glucose homeostasis and type 2 diabetes mellitus. These are the Hedgehog receptor Patched and Calpain-10, which have homology to the nematode tra-2 and tra-3 sex determination genes, respectively. Here, we have developed Fem1b knockout (Fem1b-KO) mice, with targeted inactivation of Fem1b, a homolog of the nematode fem-1 sex determination gene. We show that the Fem1b-KO mice display abnormal glucose tolerance and that this is due predominantly to defective glucose-stimulated insulin secretion. Arginine-stimulated insulin secretion is also affected. The Fem1b gene is expressed in pancreatic islets, within both beta cells and non-beta cells, and is highly expressed in INS-1E cells, a pancreatic beta-cell line. In conclusion, these data implicate Fem1b in pancreatic islet function and insulin secretion, strengthening evidence that a genetic pathway homologous to nematode sex determination may be involved in glucose homeostasis and suggesting novel genes and processes as potential candidates in the pathogenesis of diabetes mellitus.

Animals↗
PubMed2001

The concept of energy homeostasis for optimal health during training.

From all nutritional variables optimal energy supply is considered as most vital for human performance. It is postulated that lack of energy homeostasis is the basic problem in the development of overtraining. Most if not all clinical symptoms are directly or indirectly related to the physiological mechanisms of energy homeostasis. The rapidly increasing knowledge in the field of body weight control with several new regulatory neuro-peptides such as leptin, will give new opportunities to tackle this unbalance between training load and energy availability. The central role of leptin and insulin as adiposity signals has focussed attention on the anti-obesity aspects of leptin. However as member of the cytokine family, leptin is also closely linked to the immune and reproductive system. New data indicates clearly the dual function of leptin at both ends at the energy balance; starvation vs. overfeeding. It links also nutrition to the reproductive system. Lack of available energy has a much greater impact on leptin levels than exercise stress. It is suggested that application of the rapidly increasing knowledge in the obesity field will benefit the research on the mechanisms involved in the derailment of the delicate balance between training load and energy homeostasis in athletes.

Energy Metabolism↗
PubMed2000

The extracellular Ca2+-sensing receptor: central mediator of systemic calcium homeostasis.

The cloning of the G protein-coupled, extracellular calcium (Ca(2+)o)-sensing receptor (CaR) has identified a central mediator of the mechanism governing systemic Ca(2+)o homeostasis. This system enables organisms to adapt successfully to wide variations in dietary Ca(2+)o intake while maintaining near constancy of Ca(2+)o. Whereas discussions of Ca(2+)o homeostasis have generally focused on the key role of Ca(2+)o-elicited changes in parathyroid hormone secretion, the presence of the CaRs in effector tissues of this system enables direct regulation of processes (e.g. renal tubular Ca(2+) reabsorption and possibly bone formation and resorption) that add additional layers of homeostatic control. As we understand more about how the CaR regulates these tissues, we may find that it participates in other processes relevant to mineral ion homeostasis, including the control of the 1-hydroxylation and activation of vitamin D3 or reabsorption of phosphate in the renal proximal tubule. Regardless, the remarkable sensitivity of the CaR to small changes in Ca(2+)o allows adjustments in the response of the Ca(2+)o homeostatic system to increases or decreases in the intake of dietary Ca(2+), for instance, that cause barely detectable alterations in Ca(2+)o. Furthermore, the CaR likely participates in coordinating interactions among several different homeostatic control systems (including those for water, Mg(2+)o, Na(+), extracellular volume, and/or blood pressure), despite the fact that these systems are often considered to function largely independently of mineral ion metabolism.

Calcium↗
PubMed2002

Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis.

Recent studies indicate a role for the kidney in postabsorptive glucose homeostasis. The present studies were undertaken to evaluate the role of the kidney in postprandial glucose homeostasis and to compare its contribution to that of liver and skeletal muscle. Accordingly, we used the double isotope technique along with forearm and renal balance measurements to assess systemic, renal, and hepatic glucose release as well as glucose uptake by kidney, skeletal muscle, and splanchnic tissues in 10 normal volunteers after ingestion of 75 g of glucose. We found that, during the 4.5-h postprandial period, 22 +/- 2 g (30 +/- 3% of the ingested glucose) were initially extracted by splanchnic tissues. Of the remaining 53 +/- 2 g that entered the systemic circulation, 19 +/- 3 g were calculated to have been taken up by skeletal muscle and 7.5 +/- 1.7 g by the kidney (26 +/- 3 and 10 +/- 2%, respectively, of the ingested glucose). Endogenous glucose release during the postprandial period (16 +/- 2 g), calculated as the difference between overall systemic glucose appearance and the appearance of ingested glucose in the systemic circulation, was suppressed 61 +/- 3%. Surprisingly, renal glucose release increased twofold (10.6 +/- 2.5 g) and accounted for ~60% of postprandial endogenous glucose release. Hepatic glucose release (6.7 +/- 2.2 g), the difference between endogenous and renal glucose release, was suppressed 82 +/- 6%. These results demonstrate a hitherto unappreciated contribution of the kidney to postprandial glucose homeostasis and indicate that postprandial suppression of hepatic glucose release is nearly twofold greater than had been calculated in previous studies (42 +/- 4%), which had assumed that there was no renal glucose release. We postulate that increases in postprandial renal glucose release may play a role in facilitating efficient liver glycogen repletion by permitting substantial suppression of hepatic glucose release.

Blood Glucose↗
PubMed2006

Caveolin-1 and regulation of cellular cholesterol homeostasis.

Caveolae are 50- to 100-nm cell surface plasma membrane invaginations present in terminally differentiated cells. They are characterized by the presence of caveolin-1, sphingolipids, and cholesterol. Caveolin-1 is thought to play an important role in the regulation of cellular cholesterol homeostasis, a process that needs to be properly controlled to limit and prevent cholesterol accumulation and eventually atherosclerosis. We have recently generated caveolin-1-deficient [Cav-1(-/-)] mice in which caveolae organelles are completely eliminated from all cell types, except cardiac and skeletal muscle. In the present study, we examined the metabolism of cholesterol in wild-type (WT) and Cav-1(-/-) mouse embryonic fibroblasts (MEFs) and mouse peritoneal macrophages (MPMs). We observed that Cav-1(-/-) MEFs are enriched in esterified cholesterol but depleted of free cholesterol compared with their wild-type counterparts. Similarly, Cav-1(-/-) MPMs also contained less free cholesterol and were enriched in esterified cholesterol on cholesterol loading. In agreement with this finding, caveolin-1 deficiency was associated with reduced free cholesterol synthesis but increased acyl-CoA:cholesterol acyl-transferase (ACAT) activity. In wild-type MPMs, we observed that caveolin-1 was markedly upregulated on cholesterol loading. Despite these differences, cellular cholesterol efflux from MEFs and MPMs to HDL was not affected in the Cav-1-deficient cells. Neither ATP-binding cassette transporter G1 (ABCG1)- nor scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux was affected. Cellular cholesterol efflux to apolipoprotein A-I was not significantly reduced in Cav-1(-/-) MPMs compared with wild-type MPMs. However, ABCA1-mediated cholesterol efflux was clearly more sensitive to the inhibitory effects of glyburide in Cav-1(-/-) MPMs versus WT MPMs. Taken together, these findings suggest that caveolin-1 plays an important role in the regulation of intracellular cholesterol homeostasis and can modulate the activity of other proteins that are involved in the regulation of intracellular cholesterol homeostasis.

Animals↗
PubMed2000

Improved energy homeostasis of the heart in the metabolic state of exercise.

We postulate that metabolic conditions that develop systemically during exercise (high blood lactate and high nonesterified fatty acids) are favorable for energy homeostasis of the heart during contractile stimulation. We used working rat hearts perfused at physiological workload and levels of the major energy substrates and compared the metabolic and contractile responses to an acute low-to-high work transition under resting versus exercising systemic metabolic conditions (low vs. high lactate and nonesterified fatty acids in the perfusate). Glycogen preservation, resulting from better maintenance of high-energy phosphates, was a consequence of improved energy homeostasis with high fat and lactate. We explained the result by tighter coupling between workload and total beta-oxidation. Total fatty acid oxidation with high fat and lactate reflected increased availability of exogenous and endogenous fats for respiration, as evidenced by increased long-chain fatty acyl-CoA esters (LCFA-CoAs) and by an increased contribution of triglycerides to total beta-oxidation. Triglyceride turnover (synthesis and degradation) also appeared to increase. Elevated LCFA-CoAs caused high total beta-oxidation despite increased malonyl-CoA. The resulting bottleneck at mitochondrial uptake of LCFA-CoAs stimulated triglyceride synthesis. Our results suggest the following. First, both malonyl-CoA and LCFA-CoAs determine total fatty acid oxidation in heart. Second, concomitant stimulation of peripheral glycolysis and lipolysis should improve cardiac energy homeostasis during exercise. We speculate that high lactate contributes to the salutary effect by bypassing the glycolytic block imposed by fatty acids, acting as an anaplerotic substrate necessary for high tricarbocylic acid cycle flux from fatty acid-derived acetyl-CoA.

Animals↗
PubMed2005

TGF-alpha perturbs surfactant homeostasis in vivo.

To determine potential relationships between transforming growth factor (TGF)-alpha and surfactant homeostasis, the metabolism, function, and composition of surfactant phospholipid and proteins were assessed in transgenic mice in which TGF-alpha was expressed in respiratory epithelial cells. Secretion of saturated phosphatidylcholine was decreased 40-60% by expression of TGF-alpha. Although SP-A, SP-B, and SP-C mRNA levels were unchanged by expression of TGF-alpha, SP-A and SP-B content in bronchoalveolar lavage fluid was decreased. The minimum surface tension of surfactant isolated from the transgenic mice was significantly increased. Incubation of cultured normal mice type II cells with TGF-alpha in vitro did not change secretion of surfactant phosphatidylcholine and SP-B, indicating that TGF-alpha does not directly influence surfactant secretion. Expression of a dominant negative (mutant) EGF receptor in the respiratory epithelium blocked the TGF-alpha-induced changes in lung morphology and surfactant secretion, indicating that EGF receptor signaling in distal epithelial cells was required for TGF-alpha effects on surfactant homeostasis. Because many epithelial cells were embedded in fibrotic lesions caused by TGF-alpha, changes in surfactant homeostasis may at least in part be influenced by tissue remodeling that results in decreased surfactant secretion. The number of nonembedded type II cells was decreased 30% when TGF-alpha was expressed during development and was increased threefold by TGF-alpha expression in adulthood, suggesting possible alteration of type II cells on surfactant metabolism in the adult lung. Abnormalities in surfactant function and decreased surfactant level in the airways may contribute to the pathophysiology induced by TGF-alpha in both the developing and adult lung.

Animals↗
PubMed2001

SP-D and GM-CSF regulate surfactant homeostasis via distinct mechanisms.

Both surfactant protein (SP) D and granulocyte-macrophage colony-stimulating factor (GM-CSF) influence pulmonary surfactant homeostasis, with the deficiency of either protein causing marked accumulation of surfactant phospholipids in lung tissues and in the alveoli. To assess whether the effects of each gene were mediated by distinct or shared mechanisms, surfactant homeostasis and lung morphology were assessed in 1) double-transgenic mice in which both SP-D and GM-CSF genes were ablated [SP-D(-/-),GM(-/-)] and 2) transgenic mice deficient in both SP-D and GM-CSF in which the expression of GM-CSF was increased in the lung. Saturated phosphatidylcholine (Sat PC) pool sizes were markedly increased in SP-D(-/-),GM(-/-) mice, with the effects of each gene deletion on surfactant Sat PC pool sizes being approximately additive. Expression of GM-CSF in lungs of SP-D(-/-),GM(-/-) mice corrected GM-CSF-dependent abnormalities in surfactant catabolism but did not correct lung pathology characteristic of SP-D deletion. In contrast to findings in GM(-/-) mice, degradation of [(3)H]dipalmitoylphosphatidylcholine by alveolar macrophages from the SP-D(-/-) mice was normal. The emphysema and foamy macrophage infiltrates characteristic of SP-D(-/-) mice were similar in the presence or absence of GM-CSF. Taken together, these findings demonstrate the distinct roles of SP-D and GM-CSF in the regulation of surfactant homeostasis and lung structure.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2005

Effects of high-fat diets with different carbohydrate-to-protein ratios on energy homeostasis in rats with impaired brain melanocortin receptor activity.

Changes in dietary macronutrient composition and/or central nervous system neuronal activity can underlie obesity and disturbed fuel homeostasis. We examined whether switching rats from a diet with high carbohydrate content (HC; i.e., regular chow) to diets with either high fat (HF) or high fat/high protein content at the expense of carbohydrates (LC-HF-HP) causes differential effects on body weight and glucose homeostasis that depend on the integrity of brain melanocortin (MC) signaling. In vehicle-treated rats, switching from HC to either HF or LC-HF-HP feeding caused similar reductions in food intake without alterations in body weight. A reduced caloric intake (-16% in HF and LC-HF-HP groups) required to maintain or increase body weight underlay these effects. Chronic third cerebroventricular infusion of the MC receptor antagonist SHU9119 (0.5 nmol/day) produced obesity and hyperphagia with an increased food efficiency again observed during HF (+19%) and LC-HF-HP (+33%) feeding. In this case, however, HF feeding exaggerated SHU9119-induced hyperphagia and weight gain relative to HC and LC-HF-HP feeding. Relative to vehicle-treated controls, SHU9119 treatment increased plasma insulin (2.8-4 fold), leptin (7.7-15 fold), and adiponectin levels (2.4-3.7 fold), but diet effects were only observed on plasma adiponectin (HC and LC-HF-HP<HF). Finally, SHU9119-treated LC-HF-HP-fed rats were less glucose tolerant than others. Relatively low plasma adiponectin levels likely contributed to this effect. Thus HF feeding amplifies obesity induced by impaired MC signaling, provided that the carbohydrate-to-protein (C/P) ratio is high enough. Reduction of the C/P ratio within a HF diet ameliorates hyperphagia and obesity in rats with impaired MC signaling but aggravates associated disturbances in fuel homeostasis.

Animals↗
PubMed1985

Alteration of adipocyte calcium homeostasis by Escherichia coli endotoxin.

The present study evaluated calcium homeostasis in rat adipocytes after either in vivo or in vitro exposure to Escherichia coli endotoxin. Fat cells from endotoxin-treated rats showed an enhanced uptake of 45Ca. In an attempt to differentiate between 45Ca binding to the cell surface and intracellular 45Ca accumulation, adipocytes were exposed to 5 mM LaCl3. The amount of 45Ca remaining associated with lanthanum-treated adipocytes was taken to be located intracellularly and was increased in adipocytes from endotoxin-treated rats. The amount of 45Ca displaced by lanthanum was also increased in adipocytes from endotoxin-treated rats. This suggested that the endotoxin-induced increase of 45Ca accumulation included both cell surface and intracellular binding sites. Compartmental analysis of the exchange kinetics of cell-associated 45Ca with 40Ca in the medium indicated a 77% increase in the size of the cell surface compartment of adipocytes from endotoxin-treated rats compared with controls. In addition, endotoxin treatment altered the flux of calcium from the cells to the medium. In vitro exposure of freshly prepared adipocytes to 250 or 750 micrograms endotoxin/ml did not produce a perturbation of adipocyte calcium homeostasis. The results indicate that endotoxin induces alterations in the ability of adipocytes to regulate calcium translocations, suggesting that some metabolic and hormonal aspects of endotoxins' actions may be mediated through perturbation of cellular calcium homeostasis.

Adipose Tissue↗
PubMed1992

Effect of exercise training and chronic glyburide treatment on glucose homeostasis in diabetic rats.

Exercise training and sulfonylurea treatment, either individually or in combination, were evaluated for their effects on plasma glucose concentrations, oral glucose tolerance, and glucose clearance in the perfused hindquarter of diabetic rats. Female rats that were injected with streptozocin (45 mg/kg iv) and had plasma glucose concentrations between 11 and 25 mM were considered diabetic and divided into sedentary, glyburide-treated, exercise-trained, and glyburide-treated plus exercise-trained groups. The sedentary streptozocin-treated rats were severely diabetic, as indicated by elevated glucose concentrations, impaired insulin response during oral glucose tolerance tests, and lower rates of glucose clearance in hindlimb skeletal muscle. Neither 8 wk of exercise training nor 4 wk of glyburide treatment alone improved these parameters. In contrast, the diabetic rats that were both trained and treated with glyburide showed some improvement in glucose homeostasis, as evidenced by lower plasma glucose concentrations, an enhanced insulin response to an oral glucose load, and a decrease in the severity of skeletal muscle insulin resistance compared with the diabetic controls. These data suggest that glyburide treatment or exercise training alone does not alter glucose homeostasis in severely insulin-deficient diabetic rats; however, the combination of exercise training and glyburide treatment may interact to improve glucose homeostasis in these animals.

Animals↗