Reduced AMPKα2 protein expression restores glucose‐induced insulin secretion in islets from calorie‐restricted rats

Abstract

SUMMARYIn 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 b-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) AMPKa2 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 AMPKa2 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 b-cell function in islets from rats subjected to CR for 21 days.

Thiamine Supplementation Alleviates Lipopolysaccharide-Triggered Adaptive Inflammatory Response and Modulates Energy State via Suppression of NFκB/p38 MAPK/AMPK Signaling in Rumen Epithelial Cells of Goats

“…AMPK plays an important role in mammalian cell adaptation to nutritional deprivation and pathological changes [ 50 ]. AMPK can be activated when low ATP levels inhibit cellular energy consumption to regulate cellular responses to the metabolic disturbance—in other words, it is activated in response to limited available energy [ 19 ].…”

Chronic water insufficiency induced kidney damage and energy dysregulation despite reduced food intake, which improved gut microbiota in female rats

“…Each dot and bar represents the mean ± SD (n = 10). *Significantly different among all groups by one-way ANOVA at p < 0.05. a, b, c Each dot and bar with a different alphabet differs significantly by Tukey's test at p < 0.05 with lower serum insulin levels during OGTT [37], which is associated with restoring glucose-stimulated insulin secretion from islets of calorie-restricted rats. In type 2 diabetic patients, very low-calorie diets also improve β-cell function, thereby improving glycemic control [38].…”

Dietary N-carbamylglutamate or L-arginine supplementation improves hepatic energy status and mitochondrial function and inhibits the AMP-activated protein kinase-peroxisome proliferator-activated receptor γ coactivator-1α-transcription factor A pathway in intrauterine-growth-retarded suckling lambs

“…AMPK has a vital role in the cellular adaptation to nutritional deprivation in vitro, together with physiopathological stresses in vivo ( Amaral et al., 2016 ). Also, AMPK prevents cellular ATP deficiency and mediates cellular responses to metabolic stress, and can be activated at a greater AMP: ATP ratio ( Hardie et al., 1998 ).…”