Acid Amyloglucosidase and Carbohydrate Regulation - III. The Induction of Sulphonylurea-Stimulated Insulin Release and its Dependence on Intracellular Monoamines

Abstract

The induction of sulphonylurea-stimulated insulin release and its dependence on intracellular monoamine levels in the β-cells was studied in mice. Model experiments in vitro on the interaction between monoamines and purified fungal acid amyloglucosidase were performed.
1) Glibenclamide-induced hypoglycemia in mice was prolonged by pretreatment with a small dose of purified fungal acid amyloglucosidase, which itself did not influence the blood glucose level.
2) Two minutes following the intravenous injection of glibenclamide, the "free" activity of acid amyloglucosidase in islet homogenates prepared in osmotically protected media was increased. This increase was found to be dose dependent.
3) Glibenclamide-induced insulin release in adrenalectomized animals was significantly inhibited by pretreatment with the lysosomal stabilizer dexamethasone and significantly enhanced by pretreatment with the lysosomal labilizer progesterone.
4) Glibenclamide-induced insulin release in animals pretreated with a small dose of purified fungal acid amyloglucosidase was considerably enhanced. This increase was significantly inhibited following administration of the monoamine precursors L-5-hydroxytryptophan (L-5-HTP) and L-3,4-dihydroxyphenylalanine (L-DOPA) and also after pretreatment with the non-hydrazine monoamine oxidase inhibitor pargyline. L-DOPA was found to be a more potent inhibitor than L-5-HTP. Combined treatment with pargyline and L-DOPA further decreased the response.
5) Model experiments in vitro on the interaction between amines and acid amyloglucosidase activity (purified fungal acid amyloglucosidase) showed a pH-dependent inhibitory action of the monoamines dopamine (DA) and 5-hydroxytryptamine (5-HT) on amyloglucosidase activity. DA was more potent than 5-HT.
6) From the data presented it is assumed that the induction of sulphonylurea-stimulated insulin release is elicited through the following events in the β-cell: Lysosomal activation - Increase of the "free" activity of the lysosomal acid amyloglucosidase - Hydrolytic glycogenosis through acid amyloglucosidase (reaction product: glucose) - Insulin release. From a functional point of view it is proposed that lysosomes taking part in insulin secreting processes should be designated crinosomes.

Key words

Acid Amyloglucosidase - Glibenclamide - Lysosomal Activation - Plasma Insulin - Blood Glucose - Monoamines - Isolated Pancreatic Islets - Mouse