Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Immunity & Ageing
Published in: Immunity & Ageing 1/2013

Open Access 01-12-2013 | Research

Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats

Authors: Leandro Pereira de Moura, Luciana Santos Souza Pauli, Dennys Esper Cintra, Claudio Teodoro de Souza, Adelino Sanchez Ramos da Silva, Rodolfo Marinho, Maria Alice Rostom de Melo, Eduardo Rochete Ropelle, José Rodrigo Pauli

Published in: Immunity & Ageing | Issue 1/2013

Login to get access

Abstract

It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging.
Appendix
Available only for authorised users
Literature
1.
Reaven GM, Reaven EP: Age, glucose intolerance, and non-insulin dependent diabetes mellitus. J Am Geriatr Soc. 1985, 33: 286-290.CrossRefPubMed
2.
Davidson MB: The effect of aging on carbohydrate metabolism: a review of the English literature and a practical approach to the diagnosis of diabetes mellitus in the elderly. Metabolism. 1979, 28: 688-705. 10.1016/0026-0495(79)90024-6.CrossRefPubMed
3.
DeFronzo RA: Glucose intolerance and aging. Diabetes Care. 1981, 4: 493-501. 10.2337/diacare.4.4.493.CrossRefPubMed
4.
Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F: Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature. 2003, 423 (6939): 550-555. 10.1038/nature01667.CrossRefPubMed
5.
Ropelle ER, Pauli JR, Cintra DE, Frederico MJ, de Pinho RA, Velloso LA, De Souza CT: Acute exercise modulates the Foxo1/PGC-1alpha pathway in the liver of diet induced obesity rats. J Physiol. 2009, 587: 2069-2076. 10.1113/jphysiol.2008.164202.PubMedCentralCrossRefPubMed
6.
Marinho R, Ropelle ER, Cintra DE, De Souza CT, Da Silva AS, Bertoli FC, Colantonio E, D'Almeida V, Pauli JR: Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss. J Cell Physiol. 2012, 227 (7): 2917-2926. 10.1002/jcp.23037.CrossRefPubMed
7.
Johnson TO, Ermolieff J, Jirousek MR: Protein tyrosine phosphatase 1B inhibitors for diabetes. Nat Rev Drug Discovery. 2002, 1: 696-709. 10.1038/nrd895.CrossRefPubMed
8.
Kenner KA, Anyanwu E, Olefsky JM, Kusari J: Protein-tyrosine-phosphatase 1B is a negative regulator of insulin- and insulin-like growth-factor-I-stimulated signaling. J Biol Chem. 1996, 271: 9810-9816.CrossRef
9.
Byon JC, Kusari AB, Kusari J: Protein-tyrosine phosphatase-1B acts as a negative regulator of insulin signal transduction. Mol Cell Biochem. 1998, 182: 101-108. 10.1023/A:1006868409841.CrossRefPubMed
10.
Goldstein BJ, Bittner-Kowalczyk A, White MF, Harbeck M: Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the grb2 adaptor protein. J Biol Chem. 2000, 275 (6): 4283-4289. 10.1074/jbc.275.6.4283.CrossRefPubMed
11.
Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy AL: Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science. 1999, 283 (5407): 1544-1548. 10.1126/science.283.5407.1544.CrossRefPubMed
12.
Klaman LD, Boss O, Peroni OD, Kim JK, Martino JL, Zabolotny JM: Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol Cell Biol. 2000, 20 (15): 5479-5489. 10.1128/MCB.20.15.5479-5489.2000.PubMedCentralCrossRefPubMed
13.
González-Rodríguez A, Más-Gutierrez JA, Mirasierra M, Fernandez-Pérez A, Lee YJ, Ko HJ, Kim JK, Romanos E, Carrascosa JM, Ros M, Vallejo M, Rondinone CM, Valverde AM: Essential role of protein tyrosine phosphatase 1B in obesity-induced inflammation and peripheral insulin resistance during aging. Aging Cell. 2012, 11 (2): 284-296. 10.1111/j.1474-9726.2011.00786.x.PubMedCentralCrossRefPubMed
14.
Hirata AE, Alvarez-Rojas F, Carvalheira JB, Carvalho CR, Dolnikoff MS, Abdalla Saad MJ: Modulation of IR/PTP1B interaction and downstream signaling in insulin sensitive tissues of MSG-rats. Life Sci. 2003, 73 (11): 1369-1381. 10.1016/S0024-3205(03)00477-6.CrossRefPubMed
15.
Delibegovic M, Zimmer D, Kauffman C, Rak K, Hong EG, Cho YR: Liver-specific deletion of protein-tyrosine phosphatase 1B (PTP1B) improves metabolic syndrome and attenuates dietinduced endoplasmic reticulum stress. Diabetes. 2009, 58 (3): 590-599.PubMedCentralCrossRefPubMed
16.
Bence KK: Hepatic PTP1B Deficiency: The Promise of a Treatment for Metabolic Syndrome?. J Clin Metab Diabetes. 2010, 1 (1): 27-33.PubMedCentralPubMed
17.
Perseghin G, Price TB, Petersen KF, Roden M, Cline GW, Gerow K, Rothman DL, Shulman GI: Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects. N Engl J Med. 1996, 335: 1357-1362. 10.1056/NEJM199610313351804.CrossRefPubMed
18.
Houmard JA, Shaw CD, Hickey MS, Tanner CJ: Effect of short-term exercise training on insulin-stimulated PI 3-kinase activity in human skeletal muscle. Am J Physiol. 1999, 277: E1055-E1060.PubMed
19.
O’Gorman DJ, Karlsson HK, McQuaid S, Yousif O, Rahman Y, Gasparro D, Glund S, Chibalin AV, Zierath JR, Nolan JJ: Exercise training increases insulin-stimulated glucose disposal and GLUT4 (SLC2A4) protein content in patients with type 2 diabetes. Diabetologia. 2006, 49: 2983-2992. 10.1007/s00125-006-0457-3.CrossRefPubMed
20.
Luciano E, Carneiro EM, Carvalho CR, Carvalheira JB, Peres SB, Reis MA, Saad MJ, Boschero AC, Velloso LA: Endurance training improves responsiveness to insulin and modulates insulin signal transduction through the phosphatidylinositol 3-kinase/Akt-1 pathway. Eur J Endocrinol. 2002, 147 (1): 149-157. 10.1530/eje.0.1470149.CrossRefPubMed
21.
Jorge ML, de Oliveira VN, Resende NM, Paraiso LF, Calixto A, Diniz AL, Resende ES, Ropelle ER, Carvalheira JB, Espindola FS, Jorge PT, Geloneze B: The effects of aerobic, resistance, and combined exercise on metabolic control, inflammatory markers, adipocytokines, and muscle insulin signaling in patients with type 2 diabetes mellitus. Metabolism. 2011, 60 (9): 1244-1252. 10.1016/j.metabol.2011.01.006.CrossRefPubMed
22.
Heled Y, Shapiro Y, Shani Y, Moran DS, Langzam L, Barash V, Sampson SR, Meyerovitch J: Physical exercise enhances hepatic insulin signaling and inhibits phosphoenolpyruvate carboxykinase activity in diabetes-prone Psammomys obesus. Metabolism. 2004, 53 (7): 836-841. 10.1016/j.metabol.2004.02.001.CrossRefPubMed
23.
Oliveira AG, Carvalho BM, Tobar N, Ropelle ER, Pauli JR, Bagarolli RA, Guadagnini D, Carvalheira JB, Saad MJ: Physical exercise reduces circulating lipopolysaccharide and TLR4 activation and improves insulin signaling in tissues of DIO rats. Diabetes. 2011, 60 (3): 784-796. 10.2337/db09-1907.PubMedCentralCrossRefPubMed
24.
Ropelle ER, Flores MB, Cintra DE, Rocha GZ, Pauli JR, Morari J, de Souza CT, Moraes JC, Prada PO, Guadagnini D, Marin RM, Oliveira AG, Augusto TM, Carvalho HF, Velloso LA, Saad MJ, Carvalheira JB: IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibition. PLoS Biol. 2010, 24: 8(8)-
25.
Pauli JR, Ropelle ER, Cintra DE, De Souza CT, da Silva AS, Moraes JC, Prada PO, de Almeida Leme JA, Luciano E, Velloso LA, Carvalheira JB, Saad MJ: Acute exercise reverses aged-induced impairments in insulin signaling in rodent skeletal muscle. Mech Ageing Dev. 2010, 131 (5): 323-329. 10.1016/j.mad.2010.03.004.CrossRefPubMed
26.
Mohammad A, Wang J, McNeill JH: Bis(maltolato)oxovanadium(IV) inhibits the activity of PTP1B in Zucker rat skeletal muscle in vivo. Mol Cell Biochem. 2002, 229 (1–2): 125-128.CrossRefPubMed
27.
Delibegovic M, Zimmer D, Kauffman C, Rak K, Hong EG, Cho YR, Kim JK, Kahn BB, Neel BG, Bence KK: Liver-specific deletion of protein-tyrosine phosphatase 1B (PTP1B) improves metabolic syndrome and attenuates diet-induced endoplasmic reticulum stress. Diabetes. 2009, 58 (3): 590-599.PubMedCentralCrossRefPubMed
28.
Carvalho CR, Brenelli SL, Silva AC, Nunes AL, Velloso LA, Saad MJ: Effect of aging on insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in liver and muscle of rats. Endocrinology. 1996, 137 (1): 151-159. 10.1210/en.137.1.151.PubMed
29.
Ropelle ER, Pauli JR, Cintra DE, da Silva AS, De Souza CT, Guadagnini D, Carvalho BM, Caricilli AM, Katashima CK, Carvalho-Filho MA, Hirabara S, Curi R, Velloso LA, Saad MJ, Carvalheira JB: Targeted Disruption of Inducible Nitric Oxide Synthase Protects Against Aging, S-Nitrosation, and Insulin Resistance in Muscle of Male Mice. Diabetes. 2012
30.
Shimokota H, Muller DC, Fleg JL, Sorkin J, Ziemba AJ, Andres R: Age as independent determinant of glucose tolerance. Diabetes. 1991, 40: 44-51. 10.2337/diabetes.40.1.44.CrossRef
31.
Rimbert V, Boirie Y, Bedu M, Hocquette JF, Ritz P, Morio B: Muscle fat oxidative capacity is not impaired by age but by physical inactivity: association with insulin sensitivity. FASEB J. 2004, 18: 737-739.PubMed
32.
Amati F, Dube JJ, Coen PM, Stefanovic-Racic M, Toledo FG, Goodpaster BH: Physical inactivity and obesity underlie the insulin resistance of aging. Diabetes Care. 2009, 32: 1547-2154. 10.2337/dc09-0267.PubMedCentralCrossRefPubMed
33.
Boden G, Chen X, DeSantis RA, Kendrick Z: Effects of age and body fat on insulin resistance in healthy men. Diabetes Care. 1993, 16 (5): 728-733. 10.2337/diacare.16.5.728.CrossRefPubMed
34.
Barnard RJ, Lawani LO, Martin DA, Youngren JF, Singh R, Scheck SH: Effects of maturation and aging on the skeletal muscle glucose transport system. Am J Physiol. 1992, 262: E619-E626.PubMed
35.
Rocha EM, Carvalho CR, Saad MJ, Velloso LA: The influence of ageing on the insulin signalling system in rat lacrimal and salivary glands. Acta Ophthalmol Scand. 2003, 81 (6): 639-645. 10.1111/j.1395-3907.2003.00162.x.CrossRefPubMed
36.
Asante-Appiah E, Kennedy BP: Protein tyrosine phosphatases: the quest for negative regulators of insulin action. Am J Physiol Endocrinol Metab. 2003, 284: E663-E670.CrossRefPubMed
37.
Seely BL, Staubs PA, Reichart DR, Berhanu P, Milarski KL, Saltiel AR, Kusari J, Olefsky JM: Protein tyrosine phosphatase 1B interacts with the activated insulin receptor. Diabetes. 1996, 45: 1379-1385. 10.2337/diabetes.45.10.1379.CrossRefPubMed
38.
Zinker BA, Rondinone CM, Trevillyan JM, Gum RJ, Clampit JE, Waring JF, Xie N, Wilcox D, Jacobson P, Frost L, Kroeger PE, Reilly RM, Koterski S, Opgenorth TJ, Ulrich RG, Crosby S, Butler M, Murray SF, McKay RA, Bhanot S, Monia BP, Jirousek MR: PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Proc Natl Acad Sci U S A. 2002, 99 (17): 11357-11362. 10.1073/pnas.142298199.PubMedCentralCrossRefPubMed
39.
Hoene M, Lehmann R, Hennige AM, Pohl AK, Häring HU, Schleicher ED, Weigert C: Acute regulation of metabolic genes and insulin receptor substrates in the liver of mice by one single bout of treadmill exercise. J Physiol. 2009, 587: 241-252. 10.1113/jphysiol.2008.160275.PubMedCentralCrossRefPubMed
40.
Michael MD, Kulkarni RN, Postic C, Previs SF, Shulman GI, Magnuson MA, Kanh CR: Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell. 2000, 6: 87-97.CrossRefPubMed
41.
Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, Zhai Q: SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab. 2007, 6 (4): 307-319. 10.1016/j.cmet.2007.08.014.CrossRefPubMed
42.
Suwaa M, Nakanob H, Radakc Z, Kumagai S: Endurance exercise increases the SIRT1 and peroxisome proliferator-activated receptor g coactivator-1alpha protein expressions in rat skeletal muscle. Metabolism. 2008, 57: 986-998. 10.1016/j.metabol.2008.02.017.CrossRef
43.
Dumke CL, Mark Davis J, Angela Murphy E, Nieman DC, Carmichael MD, Quindry JC, Travis Triplett N, Utter AC, Gross Gowin SJ, Henson DA, McAnulty SR, McAnulty LS: Successive bouts of cycling stimulates genes associated with mitochondrial biogenesis. Eur J Appl Physiol. 2009, 107 (4): 419-427. 10.1007/s00421-009-1143-1.CrossRefPubMed
44.
Zabolotny JM, Kim YB, Welsh LA, Kershaw EE, Neel BG, Kahn BB: Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo. J Biol Chem. 2008, 283 (21): 14230-14241. 10.1074/jbc.M800061200.PubMedCentralCrossRefPubMed
45.
Ropelle ER, Pauli JR, Prada PO, de Souza CT, Picardi PK, Faria MC, Cintra DE, Fernandes MF, Flores MB, Velloso LA, Saad MJ, Carvalheira JB: Reversal of diet-induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS-1 serine phosphorylation. J Physiol. 2006, 577 (pt 3): 997-1007.PubMedCentralCrossRefPubMed
46.
Da Silva AS, Pauli JR, Ropelle ER, Oliveira AG, Cintra DE, De Souza CT, Velloso LA, Carvalheira JB, Saad MJ: Exercise intensity, inflammatory signaling, and insulin resistance in obese rats. Med Sci Sports Exerc. 2010, 42 (12): 2180-2188. 10.1249/MSS.0b013e3181e45d08.CrossRefPubMed
47.
Bonora E, Moghetti P, Zancanaro C, Cigolini M, Querena M, Cacciatori V, Corgnati A, Muggeo M: Estimates of in vivo insulin action in man: comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies. J Clin Endocrinol Metab. 1989, 68: 374-378. 10.1210/jcem-68-2-374.CrossRefPubMed
48.
Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976, 72: 248-254. 10.1016/0003-2697(76)90527-3.CrossRefPubMed
49.
Saad MJ, Maeda L, Brenelli SL, Carvalho CR, Paiva RS, Velloso LA: Defects in insulin signal transduction in liver and muscle of pregnant rats. Diabetologia. 1997, 40: 179-186. 10.1007/s001250050660.CrossRefPubMed
Metadata
Title
Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats
Authors
Leandro Pereira de Moura
Luciana Santos Souza Pauli
Dennys Esper Cintra
Claudio Teodoro de Souza
Adelino Sanchez Ramos da Silva
Rodolfo Marinho
Maria Alice Rostom de Melo
Eduardo Rochete Ropelle
José Rodrigo Pauli
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2013
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/1742-4933-10-8

Other articles of this Issue 1/2013

Immunity & Ageing 1/2013 Go to the issue

Editorial

Sex, gender and immunosenescence: a key to understand the different lifespan between men and women?

Research

Association of cytomegalovirus and other pathogens with frailty and diabetes mellitus, but not with cardiovascular disease and mortality in psycho-geriatric patients; a prospective cohort study

Research

Does aging affect the immune status? A comparative analysis in 300 healthy volunteers from France, Austria and Spain

Research

Expression of calpain-calpastatin system (CCS) member proteins in human lymphocytes of young and elderly individuals; pilot baseline data for the CALPACENT project

Research

Association of a common TLR-6 polymorphism with coronary artery disease – implications for healthy ageing?

Review

Immunosenescence in vertebrates and invertebrates
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits