Biomedical subjects

M Y Wang

Publications and source records attributed to M Y Wang.

At least 37 records · Page 2Linked to original sources

PubMed2000

A randomized trial of weighted vest use in ambulatory older adults: strength, performance, and quality of life outcomes.

BACKGROUND: Lower extremity weakness is a major risk factor for falls and hip fractures. Aging muscle is capable of responding to strengthening techniques. Strategies for providing accessible, inexpensive, safe, and effective strengthening programs for older adults are needed. OBJECTIVE: To evaluate whether use of a weighted vest improved strength, physical performance, markers of bone turnover, or health-related quality of life. DESIGN: A 27-week randomized, controlled, unmasked clinical trial. The primary outcome was peak isokinetic knee extensor strength at follow-up, adjusted for baseline strength. SETTING: Home-based program. PARTICIPANTS: A total of 62 women and men, mean age 74 years. INTERVENTIONS: Subjects were randomized to: no vest (n = 21), 3% body weight (BW) vest (n = 19), or 5% BW vest (n = 22). The vest is a nylon garment with pockets that are loaded with adjustable weights. The vest was prescribed for 2 hours daily, 4 days per week. No specific physical activities were mandated. MEASUREMENTS: All measures were made at baseline and 27 weeks. These included: knee strength and endurance by isokinetic dynamometer; timed physical performance tests; serum osteocalcin and urinary N-telopeptides; and health-related quality of life scales. RESULTS: Follow-up values of muscular strength and endurance, physical performance, bone turnover markers, and health-related quality of life did not differ by treatment assignment. The final study visit was attended by 19 (90%), 15 (80%), and 20 (91%) of the control, 3%, and 5% groups, respectively. Three permanent discontinuations of vest use occurred. CONCLUSIONS: Weighted vest use did not result in improvement in multiple domains of strength and function and did not affect bone turnover markers. We conclude that the training stimulus afforded by the vest (at the dosage tested) was below the required amount to produce strength gains or bone stimulation.

Aged↗

PubMed2000

The cadherin-catenin complex is expressed alternately with the adenomatous polyposis coli protein during rat incisor amelogenesis.

E-cadherin, a calcium-dependent cell-cell adhesion molecule, is expressed in highly specific spatiotemporal patterns throughout metazoan development, notably at sites of embryonic induction. E-cadherin also plays a critical role in regulating cell motility/adhesion, cell proliferation, and apoptosis. We have used the continuously erupting rat incisor as a system for examining the expression of E-cadherin and the associated catenins [alpha-, beta-, gamma-catenin (plakoglobin) and p120(ctn)] during amelogenesis. Using immunhistochemical techniques, we observed expression of alpha-catenin and gamma-catenin in ameloblasts throughout amelogenesis. In contrast, expression of E-cadherin, beta-catenin, and p120(ctn) was strong in presecretory, transitional, and reduced stage ameloblasts (Stages I, III, and V) but was dramatically lower in secretory and maturation stage ameloblasts (Stages II and IV). This expression alternates with the expression pattern we previously reported for the adenomatous polyposis coli protein (APC), a tumor suppressor that competes with E-cadherin for binding to beta-catenin. We suggest that alternate expression of APC and the cadherin-catenin complex is critical for the alterations in cell-cell adhesion and other differentiated cellular characteristics, such as cytoskeletal alterations, that are required for the formation of enamel by ameloblasts.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Brachial plexus catheter reservoir for the treatment of upper-extremity cancer pain: technical case report.

OBJECTIVE AND IMPORTANCE: Infiltration of the brachial plexus with anesthetics can provide relief of upper-extremity pain from invasive cancer. Because the analgesia is short-lived, however, repeated invasive treatments are necessary. We describe the implantation of a catheter reservoir system, in which anesthetic injections through a subcutaneous port resulted in anesthetic infiltration of the brachial plexus. CLINICAL PRESENTATION: A 47-year-old Hispanic man with squamous cell carcinoma of the larynx had undergone surgical resection, radiation treatment, and chemotherapy. Two years later, he had locally recurrent disease involving the brachial plexus, neck, and chest wall. The patient's pain was minimally responsive to narcotics, which also caused severe nausea and anorexia. TECHNIQUE: The brachial plexus was localized percutaneously with a needle electrode stimulator. Contrast injection under fluoroscopy confirmed entry into the plexus sheath. With use of the Seldinger technique, two Silastic catheters were placed within the brachial plexus and attached with a "Y" connector to a reservoir. The patient experienced complete relief of upper-extremity pain after a test injection with xylocaine. Thereafter, serial injections of bupivacaine with triamcinolone at 1-week intervals provided complete pain relief. After the treatments were initiated, the patient reported improved sleep and an improvement in his quality of life. CONCLUSION: A catheter reservoir system for brachial plexus analgesia can provide safe and effective analgesia for upper-extremity pain. This technique negates the need for repeated invasive procedures and avoids the complications of neurolysis.

Anesthetics, Local↗

PubMed2000

Urethane-induced hyperglycemia.

AIM: To study the effects of urethane, at anesthetic dose, on the blood glucose levels in normal rats and hyperglycemic rats, and its effects on the hypoglycemic action of exogenous insulin in alloxan-treated rats. METHODS: Blood glucose concentration was measured with the glucose oxidase method. RESULTS: Urethane at anesthetic dose 1.5 g.kg-1 increased the blood glucose levels in fasting (to 2.6 +/- 0.3 g.L-1, P < 0.01) or glucose-loaded (to 3.9 +/- 0.4 g.L-1, P < 0.01) rats. It did not modify the hyperglycemia induced by epinephrine (normal islet beta-cells) or alloxan (impaired islet beta-cells). In the rats treated with alloxan, blood glucose level decreased to 1.8 +/- 0.7 g.L-1 at 200 min after administration of insulin from control level of 7.0 +/- 2.3 g.L-1, but the hypoglycemic action of exogenous insulin was abolished by urethane. CONCLUSION: Hyperglycemic action of urethane was due to its inhibiting effect on the hypoglycemic effect of insulin, except for its known mechanism of increased sympathetic release.

Alloxan↗

PubMed2000

Patch clamp studies of motor neurons in spinal cord slices: a tool for high-resolution analysis of drug actions.

AIM: To develop a tool for detailed analysis of spinally acting anesthetic and analgesic agents. METHODS: Studies were done on visually identified motor neurons in 400 microns thick spinal cord slices from 14-23 d old rats using patch clamp techniques. Ethanol was used as a prototype general anesthetic agent. RESULTS: Cell bodies in the ventrolateral horn identified as motor neurons by retrograde fluorescent labeling had a mean dimension of 32 +/- 5 microns (x +/- s, n = 25). Mean resting potential was -62.8 +/- 2.4 mV; input resistance was 44 +/- 24 M omega (n = 19). Threshold was -44 +/- 7 mV, and action potential amplitude 101 +/- 9 mV from baseline. Ethanol concentrations at and below 50-200 mmol/L decreased motor neuron excitability to the injected current; there was no effect on resting potential, but a variable reversible increase in input resistance. Ethanol reversibly depressed the excitatory postsynaptic potential, with a dose-response relationship similar to that previously observed for the population excitatory postsynaptic potential in intact spinal cord in vitro. Ethanol also reversibly depressed currents evoked by glutamate, reducing total charge transfer to 40% +/- 26% of control (x +/- s; n = 4). CONCLUSION: Reduction of connectivity in this relatively thick slice preparation does not significantly modify drug actions. The actions of ethanol on excitatory synaptic transmission observed in intact spinal cord are in part due to postsynaptic effects on motor neurons.

Anesthetics, General↗

PubMed1999

The effect of 17beta-estradiol-DNA adducts on the replication of exon # 5 of the human suppressor gene p53.

Using a PCR technique, exon # 5 of the human tumor suppressor gene p53 was amplified and ligated into the pCRII vector and transformed into Escherichia coli INV alphaF' competent cells. The cloned exon # 5 was 184 bp long. Evidence is presented to show that after dimethyldioxirane epoxidation, 17beta-estradiol was able to form 17beta-estradiol-DNA adducts and to strongly inhibit the replication of the cloned exon # 5 producing smaller sizes of DNA fragments and introducing errors of incorporation at the 3'-end of the terminating DNAs. The errors occurred mainly at the clusters of the complementary 'G' and 'A' bases on the template strand DNA, presumably, the major sites where the 17beta-estradiol-DNA adducts were formed.

Base Sequence↗

PubMed1999

Novel form of lipolysis induced by leptin.

Hyperleptinemia causes disappearance of body fat without a rise in free fatty acids (FFA) or ketones, suggesting that leptin can deplete adipocytes of fat without releasing FFA. To test this, we measured FFA and glycerol released from adipocytes obtained from normal lean Zucker diabetic fatty rats (+/+) and incubated for 0, 3, 6, or 24 h in either 20 ng/ml recombinant leptin or 100 nM norepinephrine (NE). Whereas NE increased both FFA and glycerol release from adipocytes of +/+ rats, leptin increased glycerol release in +/+ adipocytes without a parallel increase in FFA release. In adipocytes of obese Zucker diabetic fatty rats (fa/fa) with defective leptin receptors, NE increased both FFA and glycerol release, but leptin had no effect on either. Leptin significantly lowered the mRNA of leptin and fatty acid synthase of adipocytes (FAS) (p < 0.05), and up-regulated the mRNA of peroxisome proliferator-activated receptor (PPAR)-alpha, carnitine palmitoyl transferase-1, (CPT-1), and acyl CoA oxidase (ACO) (p < 0.05). NE (100 nM) also lowered leptin mRNA (p < 0.05) but did not affect FAS, PPARalpha, ACO, or CPT-1 expression. We conclude that in normal adipocytes leptin directly decreases FAS expression, increases PPARalpha and the enzymes of FFA oxidation, and stimulates a novel form of lipolysis in which glycerol is released without a proportional release of FFA.

Acyl-CoA Oxidase↗

PubMed1999

The mechanism of epristeride against benign prostatic hyperplasia.

Epristeride, a 5alpha-reductase inhibitor, decreases prostate size and improves symptoms in men with benign prostatic hyperplasia. However, little is known about the histopathology of the prostate after treatment with epristeride. To study the relationship between apoptosis and the mechanism of epristeride in the treatment of benign prostatic hyperplasia, the induction of apoptosis by epristeride was detected and measured in vitro by: (a) observing morphological changes in cells by light microscopy; (b) comparing the relative content of dihydrotestosterone in the rat prostate epithelial cells untreated and treated with epristeride by microspectrophotometry; (c) estimating changes in cell size and DNA integrity by flow cytometry; and (d) monitoring nucleosomal DNA fragmentation by agarose gel electrophoresis. The cells treated with epristeride showed a reduction in cell size, an increase in the cytoplasm/nuclear ratio, which is indicative of the condensation of nuclear chromatin, a significant decrease in optical density at 580 nm (OD580 nm), and an oligonucleosomal ladder and a subdiploid peak of DNA characteristic of apoptosis. Therefore, the mechanism of epristeride in the treatment of benign prostatic hyperplasia might be apoptosis stimulated by decreasing dihydrotestosterone level.

Androstadienes↗

PubMed1999

Retrospective intermodality registration techniques for images of the head: surface-based versus volume-based.

The primary objective of this study is to perform a blinded evaluation of two groups of retrospective image registration techniques, using as a gold standard a prospective marker-based registration method, and to compare the performance of one group with the other. These techniques have already been evaluated individually [27]. In this paper, however, we find that by grouping the techniques as volume based or surface based, we can make some interesting conclusions which were not visible in the earlier study. In order to ensure blindness, all retrospective registrations were performed by participants who had no knowledge of the gold-standard results until after their results had been submitted. Image volumes of three modalities: X-ray computed tomography (CT), magnetic resonance (MR), and positron emission tomography (PET) were obtained from patients undergoing neurosurgery at Vanderbilt University Medical Center on whom bone-implanted fiducial markers were mounted. These volumes had all traces of the markers removed and were provided via the Internet to project collaborators outside Vanderbilt, who then performed retrospective registrations on the volumes, calculating transformations from CT to MR and/or from PET to MR. These investigators communicated their transformations, again via the Internet, to Vanderbilt, where the accuracy of each registration was evaluated. In this evaluation, the accuracy is measured at multiple volumes of interest (VOI's). Our results indicate that the volume-based techniques in this study tended to give substantially more accurate and reliable results than the surface-based ones for the CT-to-MR registration tasks, and slightly more accurate results for the PET-to-MR tasks. Analysis of these results revealed that the rotational component of error was more pronounced for the surface-based group. It was also apparent that all of the registration techniques we examined have the potential to produce satisfactory results much of the time, but that visual inspection is necessary to guard against large errors.

Algorithms↗

PubMed1999

A prospective analysis of the use of octylcyanoacrylate tissue adhesive for wound closure in pediatric neurosurgery.

OBJECTIVE: Cyanoacrylate monomers have been developed for use as skin adhesives. Previous studies have demonstrated that using this skin adhesive for the closure of traumatic lacerations results in excellent cosmesis, decreased procedure-related pain and timesavings. SURGICAL TECHNIQUE: Octylcyanoacrylate skin adhesive is applied after the placement of deep fascial sutures with close approximation of the skin edges. The adhesive is applied in liquid form and polymerizes rapidly to solid form. Multiple layers are applied forming a hard impenetrable barrier. RESULTS: This technique was prospectively evaluated in the closure of 102 elective neurosurgical operations with 142 incisions: ventriculoperitoneal shunt insertion/revision (53%) and craniotomy for tumors (10%) were the commonest procedures. There were a total of 83 scalp, 36 abdominal, 8 neck, 6 chest and 6 lumbar incisions. The mean incision length was 5.1 cm (range 0.25-50 cm). Fifty-nine percent of the wounds had previous areas of operative incisions. Complications included 1 poor cosmetic result and 4 cerebrospinal fluid (CSF) leaks. Of the 4 patients with CSF leaks, 2 required operative wound revision, and 1 required ventriculoperitoneal shunting for hydrocephalus. CONCLUSION: Cyanoacrylate skin adhesive is a viable means of obtaining cosmetic wound closure. Its use requires attention to proper skin approximation and hemostasis. In our experience, propensity for CSF leakage especially in reoperative procedures is a relative contraindication.

Adolescent↗

PubMed1999

Adenovirus-mediated overexpression of uncoupling protein-2 in pancreatic islets of Zucker diabetic rats increases oxidative activity and improves beta-cell function.

The discovery of uncoupling protein (UCP)-2, a ubiquitously expressed protein homologous to UCP-1, has raised the possibility that energy balance of cells might be regulated in tissues other than brown adipocytes. In normal pancreatic islets, UCP-2 is upregulated by leptin and is low in leptin-resistant islets of ZDF rats. To determine whether UCP-2 does, in fact, have uncoupling activity and, if so, whether such activity would favorably influence the abnormalities in leptin-unresponsive UCP-2-underexpressing islets of diabetic ZDF rats, we transferred the UCP-2 gene to the islets of diabetic ZDF rats and lean (+/+) ZDF control rats. Although ATP was reduced by 23% in both groups of islets, the ATP:ADP ratio increased by 42 and 141%, respectively. [3H]palmitate oxidation was increased by 50%, and [3H]glucose oxidation was 42-63% higher. Preproinsulin mRNA was 2.9-fold above control levels, and glucose-stimulated insulin secretion, which was negligible in control ZDF rat islets, was improved in UCP-2-overexpressing islets. The high fat content of the islets was not reduced, however. We conclude that UCP-2 has uncoupling function when overexpressed in leptin-insensitive islets and that its overexpression corrects the underexpression of the insulin gene and ameliorates glucose-stimulated insulin secretion, possibly by increasing the ATP:ADP ratio.

Adenosine Diphosphate↗

PubMed1999

Occurrence of familial nonarteritic anterior ischemic optic neuropathy in a case series.

OBJECTIVE: To report on the occurrence of familial nonarteritic anterior ischemic optic neuropathy (NAION) in our NAION series. METHODS: One hundred forty-eight consecutive retrievable cases of NAION were surveyed regarding the occurrence of NAION in other family members. Medical records of affected family members were reviewed, and clinical characteristics of documented familial NAION cases were described. RESULTS: Of 79 patients who returned the survey, four reported one or more relatives with previously diagnosed NAION. There were nine cases of documented NAION in these four families. All cases occurred in siblings, with a mean age at onset of 55 years. Six patients had second eye involvement and in five, involvement became bilateral within 4 years after initial onset. None of the patients had diabetes; two had hypertension. CONCLUSION: A small number of patients with NAION may belong to a familial subclass. Three previous reports of familial NAION further support this hypothesis.

California↗

PubMed1999

Ethanol directly depresses AMPA and NMDA glutamate currents in spinal cord motor neurons independent of actions on GABAA or glycine receptors.

Ethanol is a general anesthetic agent as defined by abolition of movement in response to noxious stimulation. This anesthetic endpoint is due to spinal anesthetic actions. This study was designed to test the hypothesis that ethanol acts directly on motor neurons to inhibit excitatory synaptic transmission at glutamate receptors. Whole cell recordings were made in visually identified motor neurons in spinal cord slices from 14- to 23-day-old rats. Currents were evoked by stimulating a dorsal root fragment or by brief pulses of glutamate. Ethanol at general anesthetic concentrations (50-200 mM) depressed both responses. Ethanol also depressed glutamate-evoked responses in the presence of tetrodotoxin (300 nM), showing that its actions are postsynaptic. Block of inhibitory gamma-aminobutyric acidA and glycine receptors by bicuculline (50 microM) and strychnine (5 microM), respectively, did not significantly reduce the effects of ethanol on glutamate currents. Ethanol also depressed glutamate-evoked currents when the inhibitory receptors were blocked and either D, L-2-amino-5-phosphonopentanoic acid (40 microM) or 6-cyano-7-nitroquinoxaline-2,3-dione disodium (10 microM) were applied to block N-methyl-D-aspartate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors, respectively. The results show that ethanol exerts direct depressant effects on both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate glutamate currents in motor neurons. Enhancement of gamma-aminobutyric acidA and glycine inhibition is not required for this effect. Direct depression of glutamatergic excitatory transmission by a postsynaptic action on motor neurons thus may contribute to general anesthesia as defined by immobility in response to a noxious stimulus.

Anesthetics↗

PubMed1998

Lipoapoptosis in beta-cells of obese prediabetic fa/fa rats. Role of serine palmitoyltransferase overexpression.

We reported that the lipoapoptosis of beta-cells observed in fat-laden islets of obese fa/fa Zucker Diabetic Fatty (ZDF) rats results from overproduction of ceramide, an initiator of the apoptotic cascade and is induced by long-chain fatty acids (FA). Whereas the ceramide of cytokine-induced apoptosis may be derived from sphingomyelin hydrolysis, FA-induced ceramide overproduction seems to be derived from FA. We therefore semiquantified mRNA of serine palmitoyltransferase (SPT), which catalyzes the first step in ceramide synthesis. It was 2-3-fold higher in fa/fa islets than in +/+ controls. [3H]Ceramide formation from [3H]serine was 2.2-4. 5-fold higher in fa/fa islets. Triacsin-C, which blocks palmitoyl-CoA synthesis, and L-cycloserine, which blocks SPT activity, completely blocked [3H]ceramide formation from [3H]serine. Islets of fa/fa rats are unresponsive to the lipopenic action of leptin, which normally depletes fat and prevents FA up-regulation of SPT. To determine the role of leptin unresponsiveness in the SPT overexpression, we transferred wild type OB-Rb cDNA to their islets; now leptin completely blocked the exaggerated FA-induced increase of SPT mRNA while reducing the fat content. Beta-cell lipoapoptosis was partially prevented in vivo by treating prediabetic ZDF rats with L-cycloserine for 2 weeks. Ceramide content and DNA fragmentation both declined 40-50%. We conclude that lipoapoptosis of ZDF rats is mediated by enhanced ceramide synthesis from FA and that blockade by SPT inhibitors prevents lipoapoptosis.

Acyltransferases↗

PubMed1998

Overexpression of leptin receptors in pancreatic islets of Zucker diabetic fatty rats restores GLUT-2, glucokinase, and glucose-stimulated insulin secretion.

The high-Km glucose transporter, GLUT-2, and the high-Km hexokinase of beta cells, glucokinase (GK), are required for glucose-stimulated insulin secretion (GSIS). GLUT-2 expression in beta cells of Zucker diabetic fatty (ZDF) rats is profoundly reduced at the onset of beta-cell dysfunction of diabetes. Because ZDF rats are homozygous for a mutation in their leptin receptor (OB-R) gene and are therefore leptin-insensitive, we expressed the wild-type OB-R gene in diabetic islets by infusing a recombinant adenovirus (AdCMV-OB-Rb) to determine whether this reversed the abnormalities. Leptin induced a rise in phosphorylated STAT3, indicating that the transferred wild-type OB-R was functional. GLUT-2 protein rose 17-fold in AdCMV-OB-Rb-treated ZDF islets without leptin, and leptin caused no further rise. GK protein rose 7-fold without and 12-fold with leptin. Preproinsulin mRNA increased 64% without leptin and rose no further with leptin, but leptin was required to restore GSIS. Clofibrate and 9-cis-retinoic acid, the partner ligands for binding to peroxisome proliferator-activator receptor alpha (PPARalpha) and retinoid X receptor, up-regulated GLUT-2 expression in islets of normal rats, but not in ZDF rats, in which PPARalpha is very low. Because the fat content of islets of diabetic ZDF rats remains high unless they are treated with leptin, it appears that restoration of GSIS requires normalization of intracellular nutrient homeostasis, whereas up-regulation of GLUT-2 and GK is leptin-independent, requiring only high expression of OB-Rb.

Animals↗

PubMed1998

Resistance to adenovirally induced hyperleptinemia in rats. Comparison of ventromedial hypothalamic lesions and mutated leptin receptors.

Leptin regulates appetite and body weight via hypothalamic targets, but it can act directly on cultured pancreatic islets to regulate their fat metabolism. To obtain in vivo evidence that leptin may act peripherally as well as centrally, we compared the effect of adenovirally induced hyperleptinemia on food intake, body weight, and islet fat content in ventromedial hypothalamic-lesioned (VMHL) rats, sham-lesioned (SL) controls, and Zucker Diabetic Fatty (ZDF) rats in which the leptin receptor is mutated. Infusion with recombinant adenovirus containing the rat leptin cDNA increased plasma leptin by approximately 20 ng/ml in VMHL and ZDF rats but had no effect on their food intake, body weight, or fat tissue weight. Caloric matching of hyperphagic VMHL rats to SL controls did not reduce their resistance to hyperleptinemia. Whereas prediabetic ZDF rats had a fourfold elevation in islet fat, in VMHL rats islet fat was normal and none of them became diabetic. Isolated islets from ZDF rats were completely resistant to the lipopenic action of leptin, while VMHL islets exhibited 50% of the normal response; caloric matching of VMHL rats to SL controls increased leptin responsiveness of their islets to 92% of controls. We conclude that leptin regulation of adipocyte fat requires an intact VMH but that islet fat content is regulated independently of the VMH.

Adenoviridae↗

PubMed1998

Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression.

Obesity causes its complications through functional and morphologic damage to remotely situated tissues via undetermined mechanisms. In one rodent model of obesity, the Zucker diabetic fatty fa/fa rat, overaccumulation of triglycerides in the pancreatic islets may be responsible for a gradual depletion of beta cells, leading to the most common complication of obesity, non-insulin-dependent diabetes mellitus. At the onset of non-insulin-dependent diabetes mellitus, the islets from fa/fa rats contain up to 100 times the fat content of islets from normal lean rats. Ultimately, about 75% of the beta cells disappear from these fat-laden islets as a consequence of apoptosis induced by long-chain fatty acids (FA). Here we quantify Bcl-2, the anti-apoptosis factor in these islets, and find that Bcl-2 mRNA and protein are, respectively, 85% and 70% below controls. In normal islets cultured in 1 mM FA, Bcl-2 mRNA declined by 68% and completely disappeared in fa/fa islets cultured in FA. In both groups, suppression was completely blocked by the fatty acyl-CoA synthetase inhibitor, triacsin C, evidence of its mediation by fatty acyl-CoA. To determine whether leptin action blocked FA-induced apoptosis, we cultured normal and fa/fa islets in 1 mM FA with or without leptin. Leptin completely blocked FA-induced Bcl-2 suppression in normal islets but had no effect on islets from fa/fa rats, which are unresponsive to leptin because of a mutation in their leptin receptors (OB-R). However, when wild-type OB-R is overexpressed in fa/fa islets, leptin completely prevented FA-induced Bcl-2 suppression and DNA fragmentation.

Adipose Tissue↗

PubMed1998

Role of peroxisome proliferator-activated receptor alpha in disease of pancreatic beta cells.

Expression of peroxisome proliferator-activated receptor alpha (PPARalpha) and enzymes of fatty acid (FA) oxidation is markedly reduced in the fat-laden, dysfunctional islets of obese, prediabetic Zucker diabetic fatty (fa/fa) rats with mutated leptin receptors (OB-R). Leptin, PPARalpha/retinoid x receptor ligands, and FA all up-regulate PPARalpha and enzymes of FA oxidation and stimulate [3H]-palmitate oxidation in normal islets but not in islets from fa/fa rats. Overexpression of normal OB-R in islets of fa/fa rats corrects all of the foregoing abnormalities and reverses the diabetic phenotype. PPARalpha is a OB-R-dependent factor required for normal fat homeostasis in islet cells.

Animals↗