Taurine supplementation increases KATP channel protein content, improving Ca2+ handling and insulin secretion in islets from malnourished mice fed on a high-fat diet

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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All contributing authors report no conflicts of interest.

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Correspondence to Rosane A. Ribeiro.

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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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Keywords

  • High-fat diet
  • Insulin secretion
  • KATP channels
  • Protein malnutrition
  • Taurine supplementation
  • Voltage-sensitive Ca2+ channels