Reduced AMPKα2 protein expression restores glucose-induced insulin secretion in islets from calorie-restricted rats.
In a state of caloric restriction (CR), improved insulin action was associated with the activation of AMP-activated kinase (AMPK). Here, we verified whether AMPK was involved in impaired β-cell function in islets from rats subjected to CR for 21 days. Eight-week-old male rats were distributed into a control (CTL) group that was fed an isocaloric diet ad libitum or a CR group that received 60% of the food consumed by the CTL group. From days 18-21, CTL and CR rats were treated with sense (CTLS and CRS) or antisense (CTLAS and CRAS) AMPKα2 oligonucleotides. Caloric restriction was associated with decreased body weight, perigonadal fat pads and insulinaemia, while higher glucose tolerance was observed in CRS rats. Antisense treatment normalized insulinaemia and glucose tolerance in CRAS rats and increased cholesterolaemia in CRAS and CTLAS groups. These effects were associated with reduced pAMPK/AMPK protein expression in the liver of rats treated with antisense oligonucleotides. Additionally, CRS islets showed higher pAMPK/AMPK content and lower glucose-induced insulin release. As expected, antisense oligonucleotides against AMPKα2 efficiently reduced pAMPK/AMPK protein in CRAS and CTLAS islets. The lower AMPK content in CRAS islets normalized the insulin secretion in islets exposed to 16.7 mM glucose. In addition, CTLAS islets presented higher insulin secretion at 2.8 and 16.7 mM glucose. These findings support the hypothesis that higher AMPK protein expression is involved in impaired β-cell function in islets from rats subjected to CR for 21 days.
Programa de Pós-Graduação em Ciências Biomédicas, Centro Universitário Hermínio Ometto, UNIARARAS, Araras, SP, Brasil.
Maria Esméria C
ME
Amaral
Universidade Federal do Rio de Janeiro, Campus UFRJ-Macaé, Macaé, RJ, Brasil.
Rosane A
RA
Ribeiro
Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brasil.
Emerielle C
EC
Vanzela
Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brasil.
Helena C
HC
Barbosa-Sampaio
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction / Q000379:methods; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017208:Rats, Wistar
D001786:Blood Glucose; D007328:Insulin; C543928:Prkaa2 protein, rat; D055372:AMP-Activated Protein Kinases; D005947:Glucose
AMP-activated kinase; caloric restriction; insulin secretion; β-cell