Related Experiment Videos
Modulation of tyrosine kinase activity has multiple actions on insulin release from the pancreatic beta-cell: studies
M Hisatomi1, T Hayakawa, H Hidaka
1Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Abstract:
We investigated the role of tyrosine kinases in the regulation of insulin release from a hamster beta-cell line, HIT T15, using selective tyrosine kinase inhibitors. Genistein increased the insulin release induced by glucose, but herbimycin A, tyrphostins and the erbstatin analogue failed to change the release. Lavendustin A at 0.1 nM-1 microM caused a concave-shaped inhibition of the insulin release stimulated by 7 mM glucose. The inhibitory effect of lavendustin A was overcome by higher concentrations of glucose. Lavendustin B, the negative control analogue, had no effect on the release. Lavendustin A at a nanomolar range progressively inhibited insulin release by high K+ (50 mM)-depolarization, whereas the inhibitor did not change the insulin release by Ca2+ ionophore (A23187). On the contrary, lavendustin A at 10 nM significantly increased insulin release when glucose-induced insulin release was enhanced by either 5 microM forskolin or 162 nM 12-O-tetradecanoylphorbol 13-acetate. Lavendustin A failed to influence the Ca(2+)-induced insulin release from HIT cells permeabilized with streptolysin-O. These findings suggest that tyrosine kinases may play versatile roles in the control of insulin release from the pancreatic beta-cell.
Insights
Tyrosine kinases influence insulin release from pancreatic beta cells. Lavendustin A showed complex effects, inhibiting glucose-stimulated release but enhancing it with other stimulants, suggesting versatile roles.
Area of Science:
- Cell Biology
- Endocrinology
- Biochemistry
Background:
- Pancreatic beta cells are crucial for insulin secretion.
- Tyrosine kinases are implicated in cellular signaling pathways.
Purpose of the Study:
- To investigate the role of tyrosine kinases in regulating insulin release from HIT T15 cells.
- To elucidate the specific mechanisms by which tyrosine kinase inhibitors affect insulin secretion.
Main Methods:
- Utilized selective tyrosine kinase inhibitors (Genistein, Herbimycin A, Tyrphostins, Erbstatin analogue, Lavendustin A/B).
- Assessed insulin release from HIT T15 cells stimulated by glucose, high K+, Ca2+ ionophore, forskolin, and phorbol ester.
- Employed streptolysin-O to permeabilize cells for Ca2+-induced release studies.
Main Results:
- Genistein enhanced glucose-induced insulin release.
- Lavendustin A inhibited glucose-stimulated insulin release in a dose-dependent manner, an effect overcome by higher glucose concentrations.
- Lavendustin A inhibited K+-stimulated insulin release but not Ca2+ ionophore-induced release.
- At specific concentrations, Lavendustin A potentiated insulin release stimulated by forskolin or phorbol ester.
- Lavendustin A did not affect Ca2+-induced insulin release in permeabilized cells.
Conclusions:
- Tyrosine kinases play multifaceted roles in regulating insulin secretion from pancreatic beta cells.
- The effects of tyrosine kinase inhibition on insulin release are context-dependent, varying with the stimulus and cellular conditions.
- Specific tyrosine kinases may be involved in distinct signaling pathways controlling insulin exocytosis.