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Melatonin inhibits insulin secretion and decreases PKA levels without interfering with glucose metabolism in rat pancreatic islets
Author(s) -
Picinato Maria Cecília,
Haber Esther Piltcher,
CipollaNeto José,
Curi Rui,
De Oliveira Carvalho Carla Roberta,
Carpinelli Angelo Rafael
Publication year - 2002
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1034/j.1600-079x.2002.02903.x
Subject(s) - medicine , endocrinology , melatonin , forskolin , insulin , pancreatic islets , protein kinase a , activator (genetics) , protein kinase c , biology , carbohydrate metabolism , chemistry , islet , signal transduction , kinase , biochemistry , receptor , stimulation
The effect of melatonin (0.1 μ M) on freshly isolated islets from adult rats was investigated. Melatonin caused a marked decrease of insulin secretion by islets in response to glucose. The mechanism involved was then examined. Melatonin did not interfere with glucose metabolism as indicated by the measurement of glucose oxidation. However, the content of the protein kinase A (PKA) catalytic α ‐subunit was significantly decreased in islets exposed to melatonin for 1 hr in the presence of 8.3 mM glucose, whereas that of the protein kinase C (PKC) α ‐subunit remained unchanged. Melatonin also inhibited forskolin‐induced insulin secretion, a well known activator of adenylate cyclase (AC) activity. This may explain the low content of insulin found in islets incubated in the presence of melatonin for 3 hr. In fact, 3′,5′ ‐cyclic adenosine monophosphate (cAMP), a product of AC activity, stimulates insulin synthesis. These findings led us to postulate that a down‐regulation of the PKA signaling pathway may be the mechanism involved in the melatonin inhibition of the process of glucose‐induced insulin secretion.