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| Author(s): |
Renato Chaves Souto Branco
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2016-08-29 |
| Examining board members: |
Everardo Magalhães Carneiro;
Rui Curi;
Patrícia Cristina Lisboa da Silva;
Helena Cristina Barbosa Sampaio;
Carmen Veríssima Ferreira
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| Advisor: | Everardo Magalhães Carneiro |
| Abstract | |
Protein malnutrition has been linked to the development of obesity as well as type 2 diabetes (T2DM) in adult life. Both disorders are associated with the dysfunction of secreting and acting processes of insulin, which is related to malfunction of insulin-producing cells metabolism, showing impaired metabolic coupling factors (MCFs) production, and the resistance of peripheral tissues to its action. Taurine (TAU) supplementation restores morpho-physiological alterations in pancreatic beta-cells and in skeletal muscle in animal obese models; however, these effects are blunted in protein malnourished rodents fed a high-fat diet (HFD). We investigated the molecular and functional mechanism associated with the generation of MCFs and mitochondrial biogenesis in beta-cells of malnourished obese mice. Moreover, we investigated the mechanism possibly involved with the absence of effects of TAU supplementation in this experimental model. Thus, C57BL/6 mice were fed a control (14% protein-C) or a protein-restricted (6% protein-R) diet for 6 weeks. Afterward, mice received a high-fat diet (HFD) for 8 weeks (CH and RH) with or without 5% TAU supplementation after weaning on their drinking water (CHT and RHT). HFD led to glucose intolerance and peripheral insulin resistance in both groups, CH and RH. In addition, HFD increased glucose-stimulated insulin secretion (GSIS) in isolated pancreatic islets of the same groups. This increment was associated with increased in pyruvate carboxylase (PYC) protein expression and generation of NADPH. TAU supplementation prevented this increment on GSIS, by modulation PYC expression as well as NADPH production only in CHT pancreatic islets. The lack of effects of TAU supplementation was most likely due to alteration of TAU transport, since Taurine Transporter expression has not been increased in RHT mice as observed in CHT. In conclusion, HFD led to increment on PYC expression and NADPH levels, which was associated with increased glucose-stimulated insulin secretion in normal- and protein-restricted obese mice. Moreover, TAU prevented this outcome in CHT mice only. Protein malnutrition followed by HFD feeding impairs this effect due to reduced Taurine Transporter expression in pancreatic islets (AU) | |
| FAPESP's process: | 11/20196-1 - INVOLVEMENT OF METABOLIC COUPLING FACTORS ON INSULIN SECRETION PROCESS IN UNDERNOURISHED MICE SUBMITED TO EXPERIMENTAL OBESITY |
| Grantee: | Renato Chaves Souto Branco |
| Support Opportunities: | Scholarships in Brazil - Doctorate |