Abstract
Pancreatic β-cells are highly sensitive to suboptimal or excess nutrients, as occurs in protein-malnutrition and obesity. Taurine (Tau) improves insulin secretion in response to nutrients and depolarizing agents. Here, we assessed the expression and function of Cav and KATP channels in islets from malnourished mice fed on a high-fat diet (HFD) and supplemented with Tau. Weaned mice received a normal (C) or a low-protein diet (R) for 6 weeks. Half of each group were fed a HFD for 8 weeks without (CH, RH) or with 5 % Tau since weaning (CHT, RHT). Isolated islets from R mice showed lower insulin release with glucose and depolarizing stimuli. In CH islets, insulin secretion was increased and this was associated with enhanced KATP inhibition and Cav activity. RH islets secreted less insulin at high K+ concentration and showed enhanced KATP activity. Tau supplementation normalized K+-induced secretion and enhanced glucose-induced Ca2+ influx in RHT islets. R islets presented lower Ca2+ influx in response to tolbutamide, and higher protein content and activity of the Kir6.2 subunit of the KATP. Tau increased the protein content of the α1.2 subunit of the Cav channels and the SNARE proteins SNAP-25 and Synt-1 in CHT islets, whereas in RHT, Kir6.2 and Synt-1 proteins were increased. In conclusion, impaired islet function in R islets is related to higher content and activity of the KATP channels. Tau treatment enhanced RHT islet secretory capacity by improving the protein expression and inhibition of the KATP channels and enhancing Synt-1 islet content.
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Abbreviations
- AUC:
-
Area under curve
- BSA:
-
Bovine serum albumin
- BW:
-
Body weight
- C:
-
Control
- Cav:
-
Voltage-sensitive Ca2+ channel
- Cavα1.2 :
-
α1.2 subunit of the Cav
- Cavβ2 :
-
β2 subunit of the Cav
- [Ca2+]i :
-
Intracellular Ca2+ concentration
- CH:
-
Control mice submitted to HFD
- CHOL:
-
Cholesterol
- CHT:
-
CH supplemented with Tau
- DZX:
-
Diazoxide
- FAs:
-
Fatty acids
- GAPDH:
-
Glyceraldehyde 3-phosphate dehydrogenase
- GLUT-2:
-
Glucose transporter 2
- HFD:
-
High-fat diet
- ipGTT:
-
Intraperitoneal glucose tolerance test
- ipITT:
-
Intraperitoneal insulin tolerance test
- KATP :
-
ATP-sensitive K+
- KBB:
-
Krebs–bicarbonate buffer
- Kir6.2:
-
Subunit 6.2 of the inward-rectifier K+ channel
- Nif:
-
Nifedipine
- PK:
-
Protein kinase
- R:
-
Protein-restricted mice
- RH:
-
R submitted to HFD
- RHT:
-
RH mice supplemented with Tau
- RIA:
-
Radioimmunoassay
- SNAP-25:
-
Synaptosomal associated protein of 25 kDa
- SNARE:
-
Soluble N-ethylmaleimide-sensitive factor attachment protein receptor
- Synt-1:
-
Syntaxin 1
- SUR1:
-
Sulfonylurea receptor 1
- Tau:
-
Taurine
- Tolb:
-
Tolbutamide
- TG:
-
Triglycerides
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Acknowledgments
This study is part of the M.Sc Thesis of Jean Franciesco Vettorazzi and was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq); Instituto Nacional de Obesidade e Diabetes (CNPq/FAPESP) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). We thank Nicola Conran for editing English.
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Vettorazzi, J.F., Ribeiro, R.A., Santos-Silva, J.C. et al. Taurine supplementation increases KATP channel protein content, improving Ca2+ handling and insulin secretion in islets from malnourished mice fed on a high-fat diet. Amino Acids 46, 2123–2136 (2014). https://doi.org/10.1007/s00726-014-1763-6
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DOI: https://doi.org/10.1007/s00726-014-1763-6