title: Insulin, not glutamine dipeptide, reduces lipases expression and prevents fat wasting and weight loss in Walker 256 tumor-bearing rats.
abstract: Cachexia is the main cause of mortality in advanced cancer patients. We investigated the effects of insulin (INS) and glutamine dipeptide (GDP), isolated or associated, on cachexia and metabolic changes induced by Walker 256 tumor in rats. INS (NPH, 40 UI/kg, sc) or GDP (1.5g/kg, oral gavage) was once-daily administered during 11 days after tumor cell inoculation. GDP, INS or INS+GDP treatments did not influence the tumor growth. However, INS and INS+GDP prevented retroperitoneal fat wasting and body weight loss of tumor-bearing rats. In consistency, INS and INS+GDP prevented the increased expression of triacylglycerol lipase (ATGL) and hormone sensitive lipase (HSL), without changing the expression of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in the retroperitoneal adipose tissue of tumor-bearing rats. INS and INS+GDP also prevented anorexia and hyperlactatemia of tumor-bearing rats. However, INS and INS+GDP accentuated the loss of muscle mass (gastrocnemius, soleus and long digital extensor) without affecting the myostatin expression in the gastrocnemius muscle and blood corticosterone. GDP treatment did not promote beneficial effects. It can be concluded that treatment with INS (INS or INS+GDP), not with GDP, prevented fat wasting and weight loss in tumor-bearing rats without reducing tumor growth. These effects might be attributed to the reduction of lipases expression (ATGL and LHS) and increased food intake. The results show the physiological function of INS in the suppression of lipolysis induced by cachexia mediators in tumor-bearing rats.
authors.affiliation: Department of Physiological Sciences, State University of Londrina, 86051-990 Londrina, PR, Brazil.
authors.forename: Hely
authors.initials: H
authors.lastname: de Morais
authors.affiliation: Department of Physiological Sciences, State University of Londrina, 86051-990 Londrina, PR, Brazil.
authors.forename: Flaviane
authors.initials: F
authors.lastname: de Fatima Silva
authors.affiliation: Department of Physiology and Biophysics, University of São Paulo, 05508-900 São Paulo, SP, Brazil.
authors.forename: Francemilson Goulart
authors.initials: FG
authors.lastname: da Silva
authors.affiliation: Department of Physiological Sciences, State University of Londrina, 86051-990 Londrina, PR, Brazil.
authors.forename: Milene Ortiz
authors.initials: MO
authors.lastname: Silva
authors.affiliation: Department of Physiological Sciences, State University of Londrina, 86051-990 Londrina, PR, Brazil.
authors.forename: Maria Fernanda Rodrigues
authors.initials: MFR
authors.lastname: Graciano
authors.affiliation: Department of Pathology, State University of Londrina, 86051-990 Londrina, PR, Brazil.
authors.forename: Maria Isabel Lovo
authors.initials: MIL
authors.lastname: Martins
authors.affiliation: Department of Physiology and Biophysics, University of São Paulo, 05508-900 São Paulo, SP, Brazil.
authors.forename: Ângelo Rafael
authors.initials: ÂR
authors.lastname: Carpinelli
authors.affiliation: Department of Clinical Medical, State University of Londrina, 86057-970 Londrina, PR, Brazil.
authors.forename: Tânia Longo
authors.initials: TL
authors.lastname: Mazucco
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, 87020-900 Maringá, PR, Brazil.
authors.forename: Roberto Barbosa
authors.initials: RB
authors.lastname: Bazotte
authors.affiliation: Department of Physiological Sciences, State University of Londrina, 86051-990 Londrina, PR, Brazil. Electronic address: hmedri@uel.br.
authors.forename: Helenir Medri
authors.initials: HM
authors.lastname: de Souza
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002100:Cachexia / Q000150:complications / Q000517:prevention & control*; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008049:Lipase / Q000378:metabolism*; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000150:complications* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D007328:Insulin; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D008049:Lipase
keywords: Cachexia; Cancer; Cytokines; Insulin resistance; Metabolic disorders