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Possible contribution of taurine to distorted glucagon secretion in intra-islet insulin deficiency: a metabolome analysis using a novel α-cell model of insulin-deficient diabetes.

Bessho M, Murase-Mishiba Y, Imagawa A, Terasaki J, Hanafusa T - PLoS ONE (2014)

Bottom Line: A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells) revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells, but also which could affect the glucagon release in IRKD cells.Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells.These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response and the resultant glucose instability in insulin-deficient diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.

ABSTRACT
Glycemic instability is a serious problem in patients with insulin-deficient diabetes, and it may be due in part to abnormal endogenous glucagon secretion. However, the intracellular metabolic mechanism(s) involved in the aberrant glucagon response under the condition of insulin deficiency has not yet been elucidated. To investigate the metabolic traits that underlie the distortion of glucagon secretion under insulin deficient conditions, we generated an αTC1-6 cell line with stable knockdown of the insulin receptor (IRKD), i.e., an in vitro α-cell model for insulin-deficient diabetes, which exhibits an abnormal glucagon response to glucose. A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells) revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells, but also which could affect the glucagon release in IRKD cells. Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells. Taurine also paradoxically exaggerated the glucagon secretion at a high glucose concentration in IRKD cells and islets with IRKD. These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response and the resultant glucose instability in insulin-deficient diabetes.

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Taurine-stimulated glucagon secretion and cell contents in control αTC1-6 cells with or without insulin.(A) Cells were preincubated for 1 h with KRB containing 5.6 mM glucose, and were subsequently stimulated for 2 h with 0, 1, 10 or 100 mM taurine and treated with or without insulin (100 nM). n = 6 in each group. (B) The total protein content and total glucagon content. n = 6 in each group. The bars represent the means ± SEM; *P<0.05, vs. vehicle-treated cells.
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pone-0113254-g007: Taurine-stimulated glucagon secretion and cell contents in control αTC1-6 cells with or without insulin.(A) Cells were preincubated for 1 h with KRB containing 5.6 mM glucose, and were subsequently stimulated for 2 h with 0, 1, 10 or 100 mM taurine and treated with or without insulin (100 nM). n = 6 in each group. (B) The total protein content and total glucagon content. n = 6 in each group. The bars represent the means ± SEM; *P<0.05, vs. vehicle-treated cells.

Mentions: Because taurine was considered to be one of the most likely candidate metabolite stimulating glucagon secretion, we determined the effects of taurine supplementation on the glucagon release and synthesis. Consequently, supplementation of taurine enhanced the glucagon secretion in a concentration-dependent manner in the αTC1-6 cells, and this increase in glucagon secretion by taurine was inhibited by adding insulin (Fig. 7A). On the other hand, taurine concentration-dependently reduced the glucagon content in these cells, and the reduction disappeared with the addition of insulin (Fig. 7B). This result suggests that insulin suppresses the stimulatory effect of taurine on glucagon secretion in the αTC1-6 cells.


Possible contribution of taurine to distorted glucagon secretion in intra-islet insulin deficiency: a metabolome analysis using a novel α-cell model of insulin-deficient diabetes.

Bessho M, Murase-Mishiba Y, Imagawa A, Terasaki J, Hanafusa T - PLoS ONE (2014)

Taurine-stimulated glucagon secretion and cell contents in control αTC1-6 cells with or without insulin.(A) Cells were preincubated for 1 h with KRB containing 5.6 mM glucose, and were subsequently stimulated for 2 h with 0, 1, 10 or 100 mM taurine and treated with or without insulin (100 nM). n = 6 in each group. (B) The total protein content and total glucagon content. n = 6 in each group. The bars represent the means ± SEM; *P<0.05, vs. vehicle-treated cells.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231115&req=5

pone-0113254-g007: Taurine-stimulated glucagon secretion and cell contents in control αTC1-6 cells with or without insulin.(A) Cells were preincubated for 1 h with KRB containing 5.6 mM glucose, and were subsequently stimulated for 2 h with 0, 1, 10 or 100 mM taurine and treated with or without insulin (100 nM). n = 6 in each group. (B) The total protein content and total glucagon content. n = 6 in each group. The bars represent the means ± SEM; *P<0.05, vs. vehicle-treated cells.
Mentions: Because taurine was considered to be one of the most likely candidate metabolite stimulating glucagon secretion, we determined the effects of taurine supplementation on the glucagon release and synthesis. Consequently, supplementation of taurine enhanced the glucagon secretion in a concentration-dependent manner in the αTC1-6 cells, and this increase in glucagon secretion by taurine was inhibited by adding insulin (Fig. 7A). On the other hand, taurine concentration-dependently reduced the glucagon content in these cells, and the reduction disappeared with the addition of insulin (Fig. 7B). This result suggests that insulin suppresses the stimulatory effect of taurine on glucagon secretion in the αTC1-6 cells.

Bottom Line: A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells) revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells, but also which could affect the glucagon release in IRKD cells.Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells.These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response and the resultant glucose instability in insulin-deficient diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine (I), Osaka Medical College, Osaka, Japan.

ABSTRACT
Glycemic instability is a serious problem in patients with insulin-deficient diabetes, and it may be due in part to abnormal endogenous glucagon secretion. However, the intracellular metabolic mechanism(s) involved in the aberrant glucagon response under the condition of insulin deficiency has not yet been elucidated. To investigate the metabolic traits that underlie the distortion of glucagon secretion under insulin deficient conditions, we generated an αTC1-6 cell line with stable knockdown of the insulin receptor (IRKD), i.e., an in vitro α-cell model for insulin-deficient diabetes, which exhibits an abnormal glucagon response to glucose. A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells) revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells, but also which could affect the glucagon release in IRKD cells. Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells. Taurine also paradoxically exaggerated the glucagon secretion at a high glucose concentration in IRKD cells and islets with IRKD. These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response and the resultant glucose instability in insulin-deficient diabetes.

Show MeSH
Related in: MedlinePlus