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A < 1.7 cM interval is responsible for Dmo1 obesity phenotypes in OLETF rats.

https://arctichealth.org/en/permalink/ahliterature47295
Source
Clin Exp Pharmacol Physiol. 2004 Jan-Feb;31(1-2):110-2
Publication Type
Article
Author
Takeshi K Watanabe
Shiro Okuno
Yuki Yamasaki
Toshihide Ono
Keiko Oga
Ayako Mizoguchi-Miyakita
Hideo Miyao
Mikio Suzuki
Hiroshi Momota
Yoshihiro Goto
Hiroichi Shinomiya
Haretsugu Hishigaki
Isamu Hayashi
Toshihiro Asai
Shigeyuki Wakitani
Toshihisa Takagi
Yusuke Nakamura
Akira Tanigami
Author Affiliation
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co. Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan. tkw_watanabe@research.otsuka.co.jp
Source
Clin Exp Pharmacol Physiol. 2004 Jan-Feb;31(1-2):110-2
Language
English
Publication Type
Article
Keywords
Animals
Animals, Congenic
Body Weight - genetics
Crosses, Genetic
Diabetes Mellitus - genetics
Female
Hyperglycemia - genetics
Hyperlipidemia - blood - genetics
Male
Obesity
Phenotype
Rats
Rats, Inbred BN
Rats, Inbred OLETF
Research Support, Non-U.S. Gov't
Abstract
1. Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes of male Otsuka Long Evans Tokushima Fatty (OLETF) rats. 2. Our congenic lines, produced by transferring Dmo1 chromosomal segments from the non-diabetic Brown Norway (BN) rat into the OLETF strain, have confirmed the strong, wide-range therapeutic effects of Dmo1 on dyslipidaemia, obesity and diabetes in the fourth (BC4) and fifth (BC5) generations of congenic animals. Analysis of a relatively small number of BC5 rats (n = 71) suggested that the critical Dmo1 interval lies within a
PubMed ID
14756694 View in PubMed
Less detail

1H-NMR metabolomic biomarkers of poor outcome after hemorrhagic shock are absent in hibernators.

https://arctichealth.org/en/permalink/ahliterature267428
Source
PLoS One. 2014;9(9):e107493
Publication Type
Article
Date
2014
Author
Lori K Bogren
Carl J Murphy
Erin L Johnston
Neeraj Sinha
Natalie J Serkova
Kelly L Drew
Source
PLoS One. 2014;9(9):e107493
Date
2014
Language
English
Publication Type
Article
Keywords
Animals
Biological Markers - blood
Hibernation
Lipids - blood
Magnetic Resonance Spectroscopy
Male
Metabolome
Rats, Sprague-Dawley
Reperfusion Injury - blood - prevention & control
Sciuridae
Shock, Hemorrhagic - blood - therapy
Treatment Outcome
Abstract
Hemorrhagic shock (HS) following trauma is a leading cause of death among persons under the age of 40. During HS the body undergoes systemic warm ischemia followed by reperfusion during medical intervention. Ischemia/reperfusion (I/R) results in a disruption of cellular metabolic processes that ultimately lead to tissue and organ dysfunction or failure. Resistance to I/R injury is a characteristic of hibernating mammals. The present study sought to identify circulating metabolites in the rat as biomarkers for metabolic alterations associated with poor outcome after HS. Arctic ground squirrels (AGS), a hibernating species that resists I/R injury independent of decreased body temperature (warm I/R), was used as a negative control.
Male Sprague-Dawley rats and AGS were subject to HS by withdrawing blood to a mean arterial pressure (MAP) of 35 mmHg and maintaining the low MAP for 20 min before reperfusing with Ringers. The animals' temperature was maintained at 37 ? 0.5 ?C for the duration of the experiment. Plasma samples were taken immediately before hemorrhage and three hours after reperfusion. Hydrophilic and lipid metabolites from plasma were then analyzed via 1H-NMR from unprocessed plasma and lipid extracts, respectively. Rats, susceptible to I/R injury, had a qualitative shift in their hydrophilic metabolic fingerprint including differential activation of glucose and anaerobic metabolism and had alterations in several metabolites during I/R indicative of metabolic adjustments and organ damage. In contrast, I/R injury resistant AGS, regardless of season or body temperature, maintained a stable metabolic homeostasis revealed by a qualitative 1H-NMR metabolic profile with few changes in quantified metabolites during HS-induced global I/R.
An increase in circulating metabolites indicative of anaerobic metabolism and activation of glycolytic pathways is associated with poor prognosis after HS in rats. These same biomarkers are absent in AGS after HS with warm I/R.
Notes
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PubMed ID
25211248 View in PubMed
Less detail

5-HT(1A) receptor antagonist p-MPPI attenuates acute ethanol effects in mice and rats.

https://arctichealth.org/en/permalink/ahliterature9998
Source
Neurosci Lett. 2002 Mar 29;322(1):1-4
Publication Type
Article
Date
Mar-29-2002
Author
Nina K Popova
Elena A Ivanova
Author Affiliation
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Lavrentyeva 10, 630090 Novosibirsk, Russia. npopova@bionet.nsc.ru
Source
Neurosci Lett. 2002 Mar 29;322(1):1-4
Date
Mar-29-2002
Language
English
Publication Type
Article
Keywords
Acute Disease
Alcohol-Induced Disorders, Nervous System - drug therapy - metabolism - physiopathology
Aminopyridines - pharmacology
Animals
Brain - drug effects - metabolism - physiopathology
Dose-Response Relationship, Drug
Drug Interactions - physiology
Drug Tolerance - physiology
Ethanol - pharmacology
Hypothermia - chemically induced - drug therapy - physiopathology
Male
Mice
Mice, Inbred C3H
Neurons - drug effects - metabolism
Piperazines - pharmacology
Rats
Rats, Wistar
Receptors, Serotonin - drug effects - metabolism
Receptors, Serotonin, 5-HT1
Research Support, Non-U.S. Gov't
Serotonin - metabolism
Serotonin Antagonists - pharmacology
Sleep - drug effects - physiology
Startle Reaction - drug effects - physiology
Abstract
The effect of a selective 5-HT(1A) antagonist, 4-(2'-methoxy-)phenyl-1-[2'-(N-2"-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (p-MPPI), on acute ethanol-induced hypothermia, sleep and suppression of acoustic startle reflex in C3H/He mice and Wistar rats was studied. Administration of p-MPPI at the doses of 0.4, 0.7 and 1.0 mg/kg reduced in a dose-dependent manner the ethanol-induced hypothermia and the sleep time and attenuated the ethanol-induced decrease of acoustic startle reflex magnitude in mice. Similar p-MPPI (0.4 mg/kg) effects on ethanol-induced sleep and hypothermia were obtained in rats. It was concluded that 5-HT(1A) receptors were involved in the mechanisms of the ethanol-induced hypothermia and sleep, and that 5-HT(1A) antagonist increased acute ethanol tolerance.
PubMed ID
11958829 View in PubMed
Less detail

5-oxo-ETE induces pulmonary eosinophilia in an integrin-dependent manner in Brown Norway rats.

https://arctichealth.org/en/permalink/ahliterature10761
Source
J Clin Invest. 1998 Dec 15;102(12):2165-72
Publication Type
Article
Date
Dec-15-1998
Author
P. Stamatiou
Q. Hamid
R. Taha
W. Yu
T B Issekutz
J. Rokach
S P Khanapure
W S Powell
Author Affiliation
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada, H2X 2P2.
Source
J Clin Invest. 1998 Dec 15;102(12):2165-72
Date
Dec-15-1998
Language
English
Publication Type
Article
Keywords
Animals
Antibodies, Monoclonal - pharmacology
Antigens, CD - metabolism
Arachidonic Acids - administration & dosage - pharmacology
Chemotactic Factors - pharmacology
Immunohistochemistry
Integrin alpha4
Integrins - metabolism
Intubation, Intratracheal - methods
Leukotrienes - pharmacology
Lung - cytology - drug effects
Macrophage-1 Antigen - metabolism
Male
Platelet Activating Factor - pharmacology
Pulmonary Eosinophilia - chemically induced
Rats
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Time Factors
Abstract
We have shown previously that the 5-lipoxygenase product 5-oxo-6,8, 11,14-eicosatetraenoic acid (5-oxo-ETE) is a highly potent eosinophil chemoattractant in vitro. To determine whether this substance can induce pulmonary eosinophil infiltration in vivo, it was administered to Brown Norway rats by tracheal insufflation. Eosinophils were then counted in lung sections that had been immunostained with an antibody to eosinophil major basic protein. 5-Oxo-ETE induced a dramatic increase in the numbers of eosinophils (ED50, 2.5 microg) around the walls of the airways, which reached maximal levels (five times control levels) between 15 and 24 h after administration, and then declined. LTB4 also induced pulmonary eosinophil infiltration with a similar ED50 but appeared to be somewhat less effective. In contrast, LTD4 and LTE4 were inactive. 5-Oxo-ETE-induced eosinophilia was unaffected by the LTB4 and PAF antagonists LY255283 and WEB 2170, respectively. However, it was inhibited by approximately 75% by monoclonal antibodies to CD49d (VLA-4) or CD11a (LFA-1) but was not significantly affected by an antibody to CD11b (Mac-1). In conclusion, 5-oxo-ETE induces pulmonary eosinophilia in Brown Norway rats, raising the possibility that it may be a physiological mediator of inflammation in asthma.
PubMed ID
9854052 View in PubMed
Less detail

6-Hydroxycleroda-3,13-dien-15,16-olide protects neuronal cells from lipopolysaccharide-induced neurotoxicity through the inhibition of microglia-mediated inflammation.

https://arctichealth.org/en/permalink/ahliterature149311
Source
Planta Med. 2010 Feb;76(2):120-7
Publication Type
Article
Date
Feb-2010
Author
Yu-Tzu Shih
Ya-Yun Hsu
Fang-Rong Chang
Yang-Chang Wu
Yi-Ching Lo
Author Affiliation
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan.
Source
Planta Med. 2010 Feb;76(2):120-7
Date
Feb-2010
Language
English
Publication Type
Article
Keywords
Animals
Anti-Inflammatory Agents - isolation & purification - pharmacology - therapeutic use
Cell Death - drug effects
Cell Line, Tumor
Diterpenes - isolation & purification - pharmacology - therapeutic use
Enzyme Inhibitors - pharmacology
Humans
Inflammation - prevention & control
Inflammation Mediators - metabolism
Lipopolysaccharides
Microglia - drug effects
Neurons - drug effects
Neurotoxicity Syndromes - prevention & control
Phytotherapy
Plant Extracts - chemistry - pharmacology - therapeutic use
Polyalthia - chemistry
Rats
Rats, Sprague-Dawley
Abstract
Polyalthia longifolia var. pendula is used as an antipyretic agent in indigenous systems of medicine. Microglia-mediated inflammation plays an important role in the pathway leading to neuronal cell death in a number of neurodegenerative diseases. The aim of this study was to investigate the effects of 6-hydroxycleroda-3,13-dien-15,16-olide (PL3) extracted from Polyalthia longifolia var. pendula on lipopolysaccharide(LPS)-induced inflammation in microglia-like HAPI cells and primary microglia cultures. In microglia-neuron co-cultures, LPS decreased the cell viability of neuroblastoma SH-SY5Y cells. LPS-induced cell death was attenuated by the NOS inhibitor, L-NAME, the COX-2 inhibitor, NS-398 or the NADPH oxidase inhibitor, DPI, respectively. In LPS-treated microglia cells, PL3 decreased the expression of iNOS, COX-2, gp91 (phox), and NF- kappaBp65, the degradation of I kappaB alpha, and the production of NO, PGE (2), iROS, and TNF- alpha. PL3 also enhanced the expression of HO-1, a cytoprotective and anti-inflammatory enzyme. Moreover, PL3 reduced LPS-activated microglia-induced cell death. The present results suggest that PL3 inhibits microglia-mediated inflammation and inflammation-related neuronal cell death. Therefore, PL3 has potential use for the treatment of inflammation-related neurodegenerative diseases.
PubMed ID
19653144 View in PubMed
Less detail

7-Alkoxyquinoline O-dealkylation by microsomes from human liver and placenta.

https://arctichealth.org/en/permalink/ahliterature64902
Source
Br J Clin Pharmacol. 1992 Nov;34(5):415-20
Publication Type
Article
Date
Nov-1992
Author
J. Hakkola
J. Mäenpää
R T Mayer
S S Park
H V Gelboin
O. Pelkonen
Author Affiliation
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Source
Br J Clin Pharmacol. 1992 Nov;34(5):415-20
Date
Nov-1992
Language
English
Publication Type
Article
Keywords
Animals
Antibodies, Monoclonal - diagnostic use
Benzyl Compounds - metabolism
Cytochrome P-450 Enzyme System - antagonists & inhibitors - metabolism
Dealkylation
Female
Humans
In Vitro
Male
Mice
Mice, Inbred Strains
Microsomes - enzymology - metabolism
Microsomes, Liver - enzymology - metabolism
Placenta - enzymology - metabolism
Pregnancy
Quinolines - metabolism
Rats
Rats, Wistar
Research Support, Non-U.S. Gov't
Smoking - metabolism
Abstract
1. The O-dealkylation of seven 7-alkoxyquinoline derivatives by human hepatic and placental microsomes and the effect of maternal cigarette smoking on placental 7-alkoxyquinoline metabolism was studied. 2. None of several monoclonal antibodies to isoenzymes of cytochrome P450 had a clear effect on metabolism of the compounds by liver microsomes. 3. Maternal cigarette smoking induced the O-dealkylation of all of the 7-alkoxyquinoline derivatives, being greatest for 7-butoxy- and 7-benzyloxyquinoline. 4. Placental 7-alkoxyquinoline metabolism induced by smoking was partially inhibited by the monoclonal antibody 1-7-1 raised against 3-methylcholanthrene-induced rat liver P450. 5. None of the 7-alkoxyquinoline O-dealkylations could be assigned specifically to any known P450 isoenzyme in human liver or placenta.
PubMed ID
1467136 View in PubMed
Less detail

70 K type IV collagenase (gelatinase).

https://arctichealth.org/en/permalink/ahliterature24598
Source
Matrix Suppl. 1992;1:45-50
Publication Type
Article
Date
1992
Author
K. Tryggvason
P. Huhtala
M. Höyhtya
E. Hujanen
T. Hurskainen
Author Affiliation
Biocenter, University of Oulu, Finland.
Source
Matrix Suppl. 1992;1:45-50
Date
1992
Language
English
Publication Type
Article
Keywords
Amino Acid Sequence
Animals
Base Sequence
Basement Membrane - metabolism
Collagenases - chemistry - genetics - immunology - physiology
Gelatinase B
Genes
Humans
Molecular Sequence Data
Molecular Weight
Neoplasm Invasiveness
Neoplasm Proteins - physiology
Rabbits
Rats
Research Support, Non-U.S. Gov't
Sequence Alignment
Substrate Specificity
Abstract
Type IV collagenase (gelatinase) is a 70,000 dalton neutral metalloproteinase that specifically cleaves type IV collagen in addition to degrading denatured collagen (gelatin). It is secreted in a latent proenzyme form that is converted proteolytically in the extracellular space to a 62,000 dalton active enzyme. The primary structure, enzymatic properties as well as gene structure, demonstrate that type IV collagenase is closely related with the other well characterized metalloproteinases, interstitial collagenase and stromelysin. However, the structure of type IV collagenase differs from the others in that it is larger and contains three internal repeats that resemble the type II domains of fibronectin. Also, initial characterization of the promoter region of the gene indicates that its regulation differs from the other proteinase genes. Type IV collagenase is presumably required for the normal turnover of basement membranes. Augmented activity is linked with the invasive potential of tumor cells and the enzyme is believed to play a major role in the penetration of basement membranes by metastatic cells. Measurements of enzyme activity and mRNA levels as well as immunostaining of a variety of tumor cells and tissues suggest that assays for the enzyme may have value in the follow-up of malignant growth.
PubMed ID
1480085 View in PubMed
Less detail

1991 Volvo Award in basic sciences. Collagen types around the cells of the intervertebral disc and cartilage end plate: an immunolocalization study.

https://arctichealth.org/en/permalink/ahliterature225725
Source
Spine (Phila Pa 1976). 1991 Sep;16(9):1030-8
Publication Type
Article
Date
Sep-1991
Author
S. Roberts
J. Menage
V. Duance
S. Wotton
S. Ayad
Author Affiliation
Charles Salt Research Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, England.
Source
Spine (Phila Pa 1976). 1991 Sep;16(9):1030-8
Date
Sep-1991
Language
English
Publication Type
Article
Keywords
Adult
Aged
Animals
Awards and Prizes
Cartilage - chemistry - pathology
Cattle
Collagen - analysis - classification
Humans
Immunoenzyme Techniques
Intervertebral Disc - chemistry - pathology
Middle Aged
Rats
Sweden
Abstract
Several types of collagen are known to exist in the intervertebral disc in addition to the fibrillar collagens, Types I and II. Although they constitute only a small percentage of the total collagen content, these minor collagens may have important functions. This study was designed to investigate the presence of Types I, II, III, IV, VI, and IX collagens in the intervertebral disc and cartilage end plate by immunohistochemistry, thereby establishing their location within the tissues. Types III and VI collagen have a pericellular distribution in animal and human tissue. No staining for Type IX collagen was present in normal human disc, but in rat and bovine intervertebral disc, it was also located pericellularly. These results show that cells of the intervertebral disc and cartilage end plate sit in fibrous capsules, forming chondrons similar to those described in articular cartilage. In pathologic tissue the amount and distribution of the collagen types, and the organization of the pericellular capsule, differ from that seen in control material.
PubMed ID
1948394 View in PubMed
Less detail

Aberrant iNOS signaling is under genetic control in rodent liver cancer and potentially prognostic for the human disease.

https://arctichealth.org/en/permalink/ahliterature92898
Source
Carcinogenesis. 2008 Aug;29(8):1639-47
Publication Type
Article
Date
Aug-2008
Author
Calvisi Diego F
Pinna Federico
Ladu Sara
Pellegrino Rossella
Muroni Maria R
Simile Maria M
Frau Maddalena
Tomasi Maria L
De Miglio Maria R
Seddaiu Maria A
Daino Lucia
Sanna Valeria
Feo Francesco
Pascale Rosa M
Author Affiliation
Department of Biomedical Sciences, Division of Experimental Pathology and Oncology, University of Sassari, 07100 Sassari, Italy.
Source
Carcinogenesis. 2008 Aug;29(8):1639-47
Date
Aug-2008
Language
English
Publication Type
Article
Keywords
Animals
Carcinoma, Hepatocellular - enzymology - epidemiology - genetics - pathology
Cell Line, Tumor
Genetic Predisposition to Disease
Humans
Incidence
Liver Neoplasms - enzymology - epidemiology - genetics - pathology
Male
Mice
Mice, Transgenic
Nitric Oxide Synthase Type II - genetics
Prognosis
Rats
Rats, Inbred BN
Rats, Inbred F344
Signal Transduction - physiology
Abstract
Mounting evidence underlines the role of inducible nitric oxide synthase (iNOS) in hepatocellular carcinoma (HCC) development, but its functional interactions with pathways involved in HCC progression remain uninvestigated. Here, we analyzed in preneoplastic and neoplastic livers from Fisher 344 and Brown Norway rats, possessing different genetic predisposition to HCC, in transforming growth factor-alpha (TGF-alpha) and c-Myc-TGF-alpha transgenic mice, characterized by different susceptibility to HCC, and in human HCC: (i) iNOS function and interactions with nuclear factor-kB (NF-kB) and Ha-RAS/extracellular signal-regulated kinase (ERK) during hepatocarcinogenesis; (ii) influence of genetic predisposition to liver cancer on these pathways and role of these cascades in determining a susceptible or resistant phenotype and (iii) iNOS prognostic value in human HCC. We found progressive iNos induction in rat and mouse liver lesions, always at higher levels in the most aggressive models represented by HCC of rats genetically susceptible to hepatocarcinogenesis and c-Myc-TGF-alpha transgenic mice. iNOS, inhibitor of kB kinase/NF-kB and RAS/ERK upregulation was significantly higher in HCC with poorer prognosis (as defined by patients' survival length) and positively correlated with tumor proliferation, genomic instability and microvascularization and negatively with apoptosis. Suppression of iNOS signaling by aminoguanidine led to decreased HCC growth and NF-kB and RAS/ERK expression and increased apoptosis both in vivo and in vitro. Conversely, block of NF-kB signaling by sulfasalazine or short interfering RNA (siRNA) or ERK signaling by UO126 caused iNOS downregulation in HCC cell lines. These findings indicate that iNOS cross talk with NF-kB and Ha-RAS/ERK cascades influences HCC growth and prognosis, suggesting that key component of iNOS signaling could represent important therapeutic targets for human HCC.
PubMed ID
18579559 View in PubMed
Less detail

Ability of insulin to modulate hepatic glucose production in aging rats is impaired by fat accumulation.

https://arctichealth.org/en/permalink/ahliterature61796
Source
Am J Physiol Endocrinol Metab. 2000 Jun;278(6):E985-91
Publication Type
Article
Date
Jun-2000
Author
G. Gupta
J A Cases
L. She
X H Ma
X M Yang
M. Hu
J. Wu
L. Rossetti
N. Barzilai
Author Affiliation
Department of Medicine, and the Diabetes Research and Training Center, Albert Einstein College of Medicine, New York, New York 10461, USA.
Source
Am J Physiol Endocrinol Metab. 2000 Jun;278(6):E985-91
Date
Jun-2000
Language
English
Publication Type
Article
Keywords
Adipose Tissue
Aging
Animals
Body Composition
Energy intake
Gluconeogenesis
Glucose - biosynthesis
Glycogen - metabolism
Insulin - pharmacology
Leptin - metabolism
Liver - drug effects - metabolism
Male
Rats
Rats, Inbred BN
Rats, Inbred F344
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Abstract
Increased total fat mass (FM) and visceral fat (VF) may account in part for age-associated decrease in hepatic insulin action. This study determined whether preventing the changes in body fat distribution abolished this defect throughout aging. We studied the F(1) hybrid of Brown Norway-Fischer 344 rats (n = 29), which we assigned to caloric restriction (CR) or fed ad libitum (AL). CR (55% of the calories consumed by AL) was initiated and used at 2 mo to prevent age-dependent increases in FM and VF. AL rats were studied at 2, 8, and 20 mo; CR rats were studied at 8 and 20 mo. VF and FM remained unchanged throughout aging in CR rats. AL-fed rats at 8 and 20 mo had over fourfold higher FM and VF compared with both CR groups. Insulin clamp studies (3 mU. kg(-1). min(-1) with somatostatin) were performed to assess hepatic insulin sensitivity. Prevention of fat accretion resulted in a marked improvement in insulin action in the suppression of hepatic glucose production (HGP) (6.3 +/- 0.3 and 7.2 +/- 1.2 mg. kg(-1). min(-1) in 8- and 20-mo CR rats vs. 8.3 +/- 0.5 and 10.8 +/- 0.9 mg. kg(-1). min(-1) in 8- and 20-mo AL rats, respectively). The rate of gluconeogenesis (by enrichment of hepatic uridine diphosphate glucose and phosphoenolpyruvate pools by [(14)C]lactate) was unchanged in all groups. The improvement in hepatic insulin action in the CR group was mostly due to effective suppression of glycogenolysis (4.4 +/- 0.3 and 4.9 +/- 0.3 mg. kg(-1). min(-1) in 8- and 20-mo CR rats vs. 5.8 +/- 0.6 and 8.2 +/- 1.0 mg. kg(-1). min(-1) in 8- and 20-mo AL rats, respectively). The results demonstrated the preservation of hepatic insulin action in aging CR rats. Therefore, body fat and its distribution are major determinants of age-associated hepatic insulin resistance.
PubMed ID
10826999 View in PubMed
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