Endurance training inhibits insulin clearance and IDE expression in Swiss mice.

Published on Mar 30, 2015in PLOS ONE2.776
· DOI :10.1371/journal.pone.0118809
José M. Costa-Júnior6
Estimated H-index: 6
(State University of Campinas),
Sandra Mara Ferreira8
Estimated H-index: 8
(State University of Campinas)
+ 8 AuthorsLuiz F. Rezende13
Estimated H-index: 13
(State University of Campinas)
Introduction Endurance training improves peripheral insulin sensitivity in the liver and the skeletal muscle, but the mechanism for this effect is poorly understood. Recently, it was proposed that insulin clearance plays a major role in both glucose homeostasis and insulin sensitivity. Therefore, our goal was to determine the mechanism by which endurance training improves insulin sensitivity and how it regulates insulin clearance in mice. Methods Mice were treadmill-trained for 4 weeks at 70–80% of maximal oxygen consumption (VO2 max) for 60 min, 5 days a week. The glucose tolerance and the insulin resistance were determined using an IPGTT and an IPITT, respectively, and the insulin decay rate was calculated from the insulin clearance. Protein expression and phosphorylation in the liver and the skeletal muscle were ascertained by Western blot. Results Trained mice exhibited an increased VO2 max, time to exhaustion, glucose tolerance and insulin sensitivity. They had smaller fat pads and lower plasma concentrations of insulin and glucose. Endurance training inhibited insulin clearance and reduced expression of IDE in the liver, while also inhibiting insulin secretion by pancreatic islets. There was increased phosphorylation of both the canonical (IR-AKT) and the non-canonical (CaMKII-AMPK-ACC) insulin pathways in the liver of trained mice, whereas only the CaMKII-AMPK pathway was increased in the skeletal muscle. Conclusion Endurance training improved glucose homeostasis not only by increasing peripheral insulin sensitivity but also by decreasing insulin clearance and reducing IDE expression in the liver.
  • References (53)
  • Citations (4)
📖 Papers frequently viewed together
13 Citations
5 Citations
575 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Motoyuki TamakiH-Index: 8
#2Yoshio FujitaniH-Index: 46
Last. Hirotaka WatadaH-Index: 60
view all 23 authors...
Recent genome-wide association studies demonstrated that common variants of solute carrier family 30 member 8 gene (SLC30A8) increase susceptibility to type 2 diabetes. SLC30A8 encodes zinc transporter-8 (ZnT8), which delivers zinc ion from the cytoplasm into insulin granules. Although it is well known that insulin granules contain high amounts of zinc, the physiological role of secreted zinc remains elusive. In this study, we generated mice with β cell–specific Slc30a8 deficiency (ZnT8KO mice) ...
134 CitationsSource
#1Hairui Yuan (Tianjin Medical University)H-Index: 9
#2Yanmei Niu (Tianjin Medical University)H-Index: 9
Last. Li Fu (Tianjin Medical University)H-Index: 10
view all 6 authors...
Aerobic exercise has beneficial effects on both weight control and skeletal muscle insulin sensitivity through a number of specific signaling proteins. To investigate the targets by which exercise exerts its effects on insulin resistance, an approach of proteomic screen was applied to detect the potential different protein expressions from skeletal muscle of insulin-resistant mice after prolonged aerobic exercise training and their sedentary controls. Eighteen C57BL/6 mice were divided into two ...
23 CitationsSource
#1Bente Klarlund Pedersen (UCPH: University of Copenhagen)H-Index: 117
#2Mark A. Febbraio (Baker IDI Heart and Diabetes Institute)H-Index: 89
During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines. The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, suc...
982 CitationsSource
#1Luiz F. Rezende (State University of Campinas)H-Index: 13
#2Gustavo J. Santos (State University of Campinas)H-Index: 7
Last. Antonio Carlos Boschero (State University of Campinas)H-Index: 39
view all 5 authors...
Aims/hypothesis Ciliary neurotrophic factor (CNTF) improves metabolic variables of obese animals with characteristics of type 2 diabetes, mainly by reducing insulin resistance. We evaluated whether CNTF was able to improve other metabolic variables in mouse models of type 2 diabetes, such as beta cell mass and insulin clearance, and whether CNTF has any effect on non-obese mice with characteristics of type 2 diabetes.
25 CitationsSource
#1Gustavo J. Santos (State University of Campinas)H-Index: 7
#2Camila Aparecida Machado de Oliveira (State University of Campinas)H-Index: 16
Last. Luiz F. Rezende (State University of Campinas)H-Index: 13
view all 4 authors...
Abstract Our group previously demonstrated that CNTF protects pancreatic islets against apoptosis induced by IL1β. In addition, it is known that AMPK knockout protects beta cells from IL1β-mediated apoptosis, however how AMPK activation leads to apoptosis remains unknown. The present study was designed to investigate the possible role of AMPK pathway modulation in CNTF protective effects against apoptosis induced by IL1β or Alloxan and how AMPK activation leads to beta cells apoptosis. First, we...
17 CitationsSource
#1Stine Maarbjerg (UCPH: University of Copenhagen)H-Index: 17
#2Lykke Sylow (UCPH: University of Copenhagen)H-Index: 18
Last. Erik A. Richter (UCPH: University of Copenhagen)H-Index: 86
view all 3 authors...
Exercise counteracts insulin resistance and improves glucose homeostasis in many ways. Apart from increasing muscle glucose uptake quickly, exercise also clearly increases muscle insulin sensitivity in the post-exercise period. This review will focus on the mechanisms responsible for this increased insulin sensitivity. It is believed that increased sarcolemmal content of the glucose transporter GLUT4 can explain the phenomenon to some extent. Surprisingly no improvement in the proximal insulin s...
79 CitationsSource
#1Crystal M. Cordes (UNMC: University of Nebraska Medical Center)H-Index: 5
#2Robert G. Bennett (UNMC: University of Nebraska Medical Center)H-Index: 24
Last. Frederick G. Hamel (UNMC: University of Nebraska Medical Center)H-Index: 27
view all 4 authors...
Insulin-degrading enzyme (IDE) is a thiol sensitive peptidase that degrades insulin and amyloid β, and has been linked to type 2 diabetes mellitus and Alzheimer's disease. We examined the thiol sensitivity of IDE using S-nitrosoglutathione, reduced glutathione, and oxidized glutathione to distinguish the effects of nitric oxide from that of the redox state. The in vitro activity of IDE was studied using either partially purified cytosolic enzyme from male Sprague-Dawley rats, or purified rat rec...
19 CitationsSource
Endurance exercise is known to enhance peripheral insulin sensitivity and reduce insulin secretion. However, it is unknown whether the latter effect is due to the reduction in plasma substrate availability or alterations in b-cell secretory machinery. Here, we tested the hypothesis that endurance exercise reduces insulin secretion by altering the intracellular energy-sensitive AMP-activated kinase (AMPK) signaling pathway. Male Wistar rats were submitted to endurance protocol training one, three...
44 CitationsSource
#1Malcolm A. Leissring (Scripps Research Institute)H-Index: 24
#2Enrico Malito (U of C: University of Chicago)H-Index: 21
Last. Dennis J. Selkoe (Brigham and Women's Hospital)H-Index: 164
view all 20 authors...
Insulin is a vital peptide hormone that is a central regulator of glucose homeostasis, and impairments in insulin signaling cause diabetes mellitus. In principle, it should be possible to enhance the activity of insulin by inhibiting its catabolism, which is mediated primarily by insulin-degrading enzyme (IDE), a structurally and evolutionarily distinctive zinc-metalloprotease. Despite interest in pharmacological inhibition of IDE as an attractive anti-diabetic approach dating to the 1950s, pote...
75 CitationsSource
Insulin-degrading enzyme (IDE) or insulysin is a highly conserved Zn2+ -dependent endopeptidase with an “inverted” HxxEH motif. In vivo, IDE contributes to regulate the steady state levels of peripheral insulin and cerebral amyloid β peptide (Aβ) of Alzheimers disease. In vitro, substrates of IDE include a broad spectrum of peptides with relevant physiological functions such as atrial natriuretic factor, insulin-like growth factor-II, transforming growth factor- α, β-endorphin, amylin or glucago...
77 CitationsSource
Cited By4
#1Isaac Asare-Bediako (Cedars-Sinai Medical Center)H-Index: 3
#2Rebecca L. Paszkiewicz (Cedars-Sinai Medical Center)H-Index: 5
Last. Richard N. Bergman (Cedars-Sinai Medical Center)H-Index: 123
view all 9 authors...
Hyperinsulinemia, accompanied by reduced first-pass hepatic insulin extraction (FPE) and increased secretion, is a primary response to insulin resistance. Different in vivo methods are used to esti...
3 CitationsSource
#1Mirian Ayumi Kurauti (State University of Campinas)H-Index: 7
#2Ricardo Freitas-Dias (State University of Campinas)H-Index: 3
Last. José M. Costa-Júnior (State University of Campinas)H-Index: 6
view all 11 authors...
The effects of exercise on insulin clearance and IDE expression are not yet fully elucidated. Here, we have explored the effect of acute exercise on insulin clearance and IDE expression in lean mice. Male Swiss mice were subjected to a single bout of exercise on a speed/angle controlled treadmill for 3-h at approximately 60–70% of maximum oxygen consumption. As expected, acute exercise reduced glycemia and insulinemia, and increased insulin tolerance. The activity of AMPK-ACC, but not of IR-Akt,...
8 CitationsSource
#1Mirian Ayumi Kurauti (State University of Campinas)H-Index: 7
#2José M. Costa-Júnior (State University of Campinas)H-Index: 6
Last. Antonio Carlos Boschero (State University of Campinas)H-Index: 39
view all 8 authors...
13 CitationsSource
This study examined whether conjugated linoleic acid (CLA) supplementation affects insulin sensitivity and peroxisome proliferator-activated receptor gamma (PPAR-γ) and glucose transporter type 4 (GLUT-4) protein expressions in the skeletal muscles of rats during endurance exercise.Sprague-Dawley male rats were randomly divided into HS (high-fat diet (HFD) sedentary group, n = 8), CS (1.0% CLA supplemented HFD sedentary group, n = 8), and CE (1.0% CLA supplemented HFD exercise group, n = 8). The...
3 CitationsSource