Modulation of tyrosine kinase activity has multiple actions on insulin release from the pancreatic beta-cell: studies with lavendustin A.
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.
Hisatomi
M
M
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Hayakawa
T
T
Hidaka
H
H
Niki
I
I
D000818:Animals; D016227:Benzoquinones; D002478:Cells, Cultured; D006224:Cricetinae; D019833:Genistein; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D020032:Tyrphostins
D016227:Benzoquinones; D007328:Insulin; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D009570:Nitriles; D010636:Phenols; D011809:Quinones; D020032:Tyrphostins; C079836:tyrphostin 25; D017828:Rifabutin; C062898:lavendustin A; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D005947:Glucose