BACKGROUND: Aging-related hyperglycemia is associated with increased oxidative stress and diminished muscle glucose transporter-4 (Glut4) that may be regulated, at least in part, by the mitogen-activated protein kinases (MAPK). METHODS: To test the possibility that aging-related hyperglycemia can be prevented by pharmacological manipulation of MAPK hyperactivation, aged (27-month old) Fischer 344/NNiaHSD x Brown Norway/BiNia F1 (F344BN) rats were administered acetaminophen (30 mg/kg body weight/day) for 6 months in drinking water. RESULTS: Hepatic histopathology, serum aspartate aminotransferase and alanine aminotransferase analyses suggested that chronic acetaminophen did not cause hepatotoxicity. Compared with adult (6-month) and aged (27-month) rats, very aged rats (33-month) had higher levels of blood glucose, phosphorylation of soleus p38-MAPK and extracellular-regulated kinase 1/2 (ERK1/2), superoxide and oxidatively modified proteins (p<0.05), and these changes were associated with decreased soleus Glut4 protein abundance (p<0.05). Chronic acetaminophen treatment attenuated age-associated increase in blood glucose by 61.3% (p<0.05) and increased soleus Glut4 protein by 157.2% (p<0.05). These changes were accompanied by diminished superoxide levels, decrease in oxidatively modified proteins (-60.8%; p<0.05) and reduced p38-MAPK and ERK1/2 hyperactivation (-50.4% and -35.4%, respectively; p<0.05). CONCLUSIONS: These results suggest that acetaminophen may be useful for the treatment of age-associated hyperglycemia.
BACKGROUND: Aging-related hyperglycemia is associated with increased oxidative stress and diminished muscle glucose transporter-4 (Glut4) that may be regulated, at least in part, by the mitogen-activated protein kinases (MAPK). METHODS: To test the possibility that aging-related hyperglycemia can be prevented by pharmacological manipulation of MAPK hyperactivation, aged (27-month old) Fischer 344/NNiaHSD x Brown Norway/BiNia F1 (F344BN) rats were administered acetaminophen (30 mg/kg body weight/day) for 6 months in drinking water. RESULTS: Hepatic histopathology, serum aspartate aminotransferase and alanine aminotransferase analyses suggested that chronic acetaminophen did not cause hepatotoxicity. Compared with adult (6-month) and aged (27-month) rats, very aged rats (33-month) had higher levels of blood glucose, phosphorylation of soleus p38-MAPK and extracellular-regulated kinase 1/2 (ERK1/2), superoxide and oxidatively modified proteins (p<0.05), and these changes were associated with decreased soleus Glut4 protein abundance (p<0.05). Chronic acetaminophen treatment attenuated age-associated increase in blood glucose by 61.3% (p<0.05) and increased soleus Glut4 protein by 157.2% (p<0.05). These changes were accompanied by diminished superoxide levels, decrease in oxidatively modified proteins (-60.8%; p<0.05) and reduced p38-MAPK and ERK1/2 hyperactivation (-50.4% and -35.4%, respectively; p<0.05). CONCLUSIONS: These results suggest that acetaminophen may be useful for the treatment of age-associated hyperglycemia.
Authors: Kevin M Rice; Nandini D P K Manne; Murali K Gadde; Satyanarayana Paturi; Ravikumar Arvapalli; Eric Blough Journal: Age (Dordr) Date: 2015-03-28
Authors: Miaozong Wu; Anjaiah Katta; Murali K Gadde; Hua Liu; Sunil K Kakarla; Jacqueline Fannin; Satyanarayana Paturi; Ravi K Arvapalli; Kevin M Rice; Yeling Wang; Eric R Blough Journal: PLoS One Date: 2009-07-29 Impact factor: 3.240
Authors: Markus Lundgren; Leigh Johnson Steed; Roy Tamura; Berglind Jonsdottir; Patricia Gesualdo; Claire Crouch; Maija Sjöberg; Gertie Hansson; William A Hagopian; Anette G Ziegler; Marian J Rewers; Åke Lernmark; Jorma Toppari; Jin-Xiong She; Beena Akolkar; Jeffrey P Krischer; Michael J Haller; Helena Elding Larsson Journal: BMC Pediatr Date: 2017-05-16 Impact factor: 2.125