Limits...
Glinide, but not sulfonylurea, can evoke insulin exocytosis by repetitive stimulation: imaging analysis of insulin exocytosis by secretagogue-induced repetitive stimulations.

Aoyagi K, Ohara-Imaizumi M, Nishiwaki C, Nakamichi Y, Nagamatsu S - Exp Diabetes Res (2009)

Bottom Line: To investigate the different effects between sulfonylurea (SU) and glinide drugs in insulin secretion, pancreatic beta-cells were repeatedly stimulated with SU (glimepiride) or glinide (mitiglinide).Glimepiride, but not glucose and mitiglinide, induced abnormally sustained [Ca(2+)](i) elevations and reductions of docked insulin granules on the plasma membrane.Our data suggest that the effect of glinide on insulin secretory mechanisms is similar to that of glucose.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan.

ABSTRACT
To investigate the different effects between sulfonylurea (SU) and glinide drugs in insulin secretion, pancreatic beta-cells were repeatedly stimulated with SU (glimepiride) or glinide (mitiglinide). Total internal reflection fluorescent (TIRF) microscopy revealed that secondary stimulation with glimepiride, but not glucose and mitiglinide, failed to evoke fusions of insulin granules although primary stimulation with glucose, glimepiride, and mitiglinide induced equivalent numbers of exocytotic responses. Glimepiride, but not glucose and mitiglinide, induced abnormally sustained [Ca(2+)](i) elevations and reductions of docked insulin granules on the plasma membrane. Our data suggest that the effect of glinide on insulin secretory mechanisms is similar to that of glucose.

Show MeSH
The numbers of docked insulin granules just before the second stimulation. Results are mean  ±   S.E.M percentage of the numbers of docked insulin granules just before the first stimulation (N = 12, 9, and 10 for 16.7 mM glucose, mitiglinide, and glimepiride, resp.).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2801449&req=5

fig3: The numbers of docked insulin granules just before the second stimulation. Results are mean ± S.E.M percentage of the numbers of docked insulin granules just before the first stimulation (N = 12, 9, and 10 for 16.7 mM glucose, mitiglinide, and glimepiride, resp.).

Mentions: It is of note that the second glimepiride stimulation failed to induce the exocytotic response even though [Ca2+]i during the second stimulus was equivalent to that induced by the first glimepiride stimulation. Thus, we assumed that the abnormally sustained [Ca2+]i elevation induced by glimepiride would affect the exocytotic process that is probably involved in the regulation of insulin granule motility, because the exocytotic responses evoked by glimepiride were largely composed of newcomer granules which must move a long distance from the cytosol to the plasma membrane. To this end, we investigated the numbers of docked insulin granules on the plasma membrane after a 15-minute interval following the first stimulation because the motility of insulin granules should be reflected by the number of docked insulin granules after the onset of stimulation [6]. As shown in Figure 3, the first high glucose and mitiglinide stimuli did not affect the numbers of docked insulin granules on the plasma membrane. On the other hand, the number of docked insulin granules was decreased to 58.0 ± 4.5% by the first glimepiride stimulation despite the 15-minute recovery period, suggesting that glimepiride, but not mitiglinide, would impair the intracellular motility of insulin granules and their recruitment to the plasma membrane. These results suggest that the abnormally sustained [Ca2+]i elevation by primary glimepiride stimulation impaired insulin granule motility, which might be the cause of the unresponsiveness to the second glimepiride stimulation.


Glinide, but not sulfonylurea, can evoke insulin exocytosis by repetitive stimulation: imaging analysis of insulin exocytosis by secretagogue-induced repetitive stimulations.

Aoyagi K, Ohara-Imaizumi M, Nishiwaki C, Nakamichi Y, Nagamatsu S - Exp Diabetes Res (2009)

The numbers of docked insulin granules just before the second stimulation. Results are mean  ±   S.E.M percentage of the numbers of docked insulin granules just before the first stimulation (N = 12, 9, and 10 for 16.7 mM glucose, mitiglinide, and glimepiride, resp.).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2801449&req=5

fig3: The numbers of docked insulin granules just before the second stimulation. Results are mean ± S.E.M percentage of the numbers of docked insulin granules just before the first stimulation (N = 12, 9, and 10 for 16.7 mM glucose, mitiglinide, and glimepiride, resp.).
Mentions: It is of note that the second glimepiride stimulation failed to induce the exocytotic response even though [Ca2+]i during the second stimulus was equivalent to that induced by the first glimepiride stimulation. Thus, we assumed that the abnormally sustained [Ca2+]i elevation induced by glimepiride would affect the exocytotic process that is probably involved in the regulation of insulin granule motility, because the exocytotic responses evoked by glimepiride were largely composed of newcomer granules which must move a long distance from the cytosol to the plasma membrane. To this end, we investigated the numbers of docked insulin granules on the plasma membrane after a 15-minute interval following the first stimulation because the motility of insulin granules should be reflected by the number of docked insulin granules after the onset of stimulation [6]. As shown in Figure 3, the first high glucose and mitiglinide stimuli did not affect the numbers of docked insulin granules on the plasma membrane. On the other hand, the number of docked insulin granules was decreased to 58.0 ± 4.5% by the first glimepiride stimulation despite the 15-minute recovery period, suggesting that glimepiride, but not mitiglinide, would impair the intracellular motility of insulin granules and their recruitment to the plasma membrane. These results suggest that the abnormally sustained [Ca2+]i elevation by primary glimepiride stimulation impaired insulin granule motility, which might be the cause of the unresponsiveness to the second glimepiride stimulation.

Bottom Line: To investigate the different effects between sulfonylurea (SU) and glinide drugs in insulin secretion, pancreatic beta-cells were repeatedly stimulated with SU (glimepiride) or glinide (mitiglinide).Glimepiride, but not glucose and mitiglinide, induced abnormally sustained [Ca(2+)](i) elevations and reductions of docked insulin granules on the plasma membrane.Our data suggest that the effect of glinide on insulin secretory mechanisms is similar to that of glucose.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan.

ABSTRACT
To investigate the different effects between sulfonylurea (SU) and glinide drugs in insulin secretion, pancreatic beta-cells were repeatedly stimulated with SU (glimepiride) or glinide (mitiglinide). Total internal reflection fluorescent (TIRF) microscopy revealed that secondary stimulation with glimepiride, but not glucose and mitiglinide, failed to evoke fusions of insulin granules although primary stimulation with glucose, glimepiride, and mitiglinide induced equivalent numbers of exocytotic responses. Glimepiride, but not glucose and mitiglinide, induced abnormally sustained [Ca(2+)](i) elevations and reductions of docked insulin granules on the plasma membrane. Our data suggest that the effect of glinide on insulin secretory mechanisms is similar to that of glucose.

Show MeSH