Limits...
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.

Show MeSH

Related in: MedlinePlus

Time course of [3H] taurine and amino acid uptake in control and IRKD αTC1-6 cells.n = 4 in each group. The data are expressed as the means ± SEM; *P<0.05, control vs. IRKD.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4231115&req=5

pone-0113254-g005: Time course of [3H] taurine and amino acid uptake in control and IRKD αTC1-6 cells.n = 4 in each group. The data are expressed as the means ± SEM; *P<0.05, control vs. IRKD.

Mentions: We examined whether IR knockdown affected the uptake and synthesis of taurine, arginine, glutamine and leucine in αTC1-6 cells. Figure 5A shows the time-dependent [3H] taurine uptake for 120 min in the control and IRKD cells. The IRKD cells exhibited significantly higher levels of taurine uptake than control cells from 30 to 120 min. On the other hand, the arginine uptake in the IRKD cells was shown to decrease from 60 to 120 min compared with the controls (Fig. 5B). There were no significant differences in the glutamine and leucine uptake between the IRKD and control cells (Figs. 5C and D). It is noteworthy that the uptake of labeled nutrients that are metabolized into CO2, H2O and other secreted metabolites would not be included in the measurement, because the assay measures the radioactivity trapped in the cells, so the values obtained in this study may have underestimated the actual values.


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)

Time course of [3H] taurine and amino acid uptake in control and IRKD αTC1-6 cells.n = 4 in each group. The data are expressed as the means ± SEM; *P<0.05, control vs. IRKD.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0113254-g005: Time course of [3H] taurine and amino acid uptake in control and IRKD αTC1-6 cells.n = 4 in each group. The data are expressed as the means ± SEM; *P<0.05, control vs. IRKD.
Mentions: We examined whether IR knockdown affected the uptake and synthesis of taurine, arginine, glutamine and leucine in αTC1-6 cells. Figure 5A shows the time-dependent [3H] taurine uptake for 120 min in the control and IRKD cells. The IRKD cells exhibited significantly higher levels of taurine uptake than control cells from 30 to 120 min. On the other hand, the arginine uptake in the IRKD cells was shown to decrease from 60 to 120 min compared with the controls (Fig. 5B). There were no significant differences in the glutamine and leucine uptake between the IRKD and control cells (Figs. 5C and D). It is noteworthy that the uptake of labeled nutrients that are metabolized into CO2, H2O and other secreted metabolites would not be included in the measurement, because the assay measures the radioactivity trapped in the cells, so the values obtained in this study may have underestimated the actual values.

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