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|Title:||Altered mitochondrial metabolism is involved with increased amplifying pathways modulation of insulin secretion in protein malnourished obese mice|
|Author:||Zoppi, C. C.|
Leite, N. C.
Branco, R. C. S.
Paula, F. M. M.
Borck, P. C.
Vettorazzi, J. F.
Carneiro, E. M.
|Abstract:||Glucose-induced insulin secretion (GIIS) stimulates dependent and independent mechanisms of KATP channels. Low protein and high-fat diets, during important stages of development favor obesity progress inducing several changes in pancreatic islets. The changes on the independent mechanisms of KATP channels, also called amplifying pathways, induced by the combination of these two treatments are unknown. Our aim was investigating the role of these pathways on GIIS modulation of malnourished obese mice. After weaning, 21 days old male C57BL-6 mice were randomly assigned into the control group (C) which received a normo-protein diet (14% protein) during 105 days; the control-high fat diet (HFD) (CH) received normo-protein diet for 45 days and after that was treated with a HFD (60% fat) for 60 days. The protein restricted R and RH groups were fed with a low protein diet (LPD) (6% protein), receiving the same HFD treatment. Insulin tolerance was assessed by euglycemic-hyperinsulinemic clamp. In order to investigate amplifying pathways control of insulin secretion, we incubated islets with glucose (G2.8; 11.1; 22.2 mM) in the presence of K+ (30 mM) and diazoxide (250 μm). Insulin content was measured by radioimmunoassay. Protein kinases A and C and mitochondrial metabolism were also assessed. HFD decreased glucose uptake (C=25.6±2.1/CH=15.9±2.36; R=50.0±5.1/RH=18.18±3.9 mg/kg/min). GIIS was higher in animals fed with HFD (G22.2 C=1.58±0.18/CH=3.0±0.3; R=1.08±0.12/RH= 1.8±0.3 ng/mL/hour/islet). The influence of amplifying pathways in insulin secretion was lower in R animals (G22.2 C=0.757±0.1; R=0.33± 0.09 ng/mL/hour/islet). There were no differences among C and CH in all glucose concentrations. Additionally, the role of amplifying pathways was higher in RH (G22.2 R=0.33±0.09; RH=1.67±0.22). Whereas PKA and PKC content were not altered, ATP production displayed a trend to be reduced in RH. Basal mitochondrial membrane potential and glutamate dehydrogenase (GDH) protein content were nearly 40 and 50% higher, respectively. Higher amplifying pathway modulation of insulin secretion of obese protein malnourished mice is associated with impaired mitochondrial function and GDH content. This could be one of the mechanisms reprogrammed by early protein malnutrition, since this effect does not appear in animals fed with a normal protein plus HFD.|
Insulina - Secreção
Dieta com restrição de proteínas
|Citation:||Altered Mitochondrial Metabolism Is Involved With Increased Amplifying Pathways Modulation Of Insulin Secretion In Protein Malnourished Obese Mice. Springer, v. 58, p. S340-S340 SEP-2015.|
|Appears in Collections:||IB - Artigos e Outros Documentos|
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