Effects of insulin on norepinephrine- and acetylcholine-induced membrane currents of pinealocytes from healthy Wistar and type 2 diabetic GK rats.

The neurohormone melatonin is synthesized by the pineal gland under the stimulation of norepinephrine (NE). Its synthesis is inhibited by acetylcholine (ACh) and by insulin. Type 2 diabetic Goto Kakizaki (GK) rats have higher insulin and lower melatonin plasma levels than healthy Wistar rats.

Differential and day-time dependent expression of nuclear receptors RORα, RORβ, RORγ and RXRα in the rodent pancreas and islet.

The retinoic-acid-related receptor family of orphan receptors (RORs) act as transcriptional activators or repressors. One of their functions involves integrated actions within circadian oscillators, particularly of the periphery. The present paper describes differential expression of the orphan receptors RORα, RORβ and RORγ and of the nuclear retinoid receptor RXRα in the pancreas and islet of rats.

Phosphorylation of cyclic AMP-response element-binding protein (CREB) is influenced by melatonin treatment in pancreatic rat insulinoma β-cells (INS-1).

The pineal hormone melatonin exerts its influence on the insulin secretion of pancreatic islets by a variety of signalling pathways. The purpose of the present study was to analyse the impact of melatonin on the phosphorylated transcription factor cAMP-response element-binding protein (pCREB). In pancreatic rat insulinoma β-cells (INS-1), pCREB immunofluorescence intensities in cell nuclei using digitised confocal image analysis were measured to semi-quantify differences in the pCREB immunoreactivity (pCREB-ir) caused by different treatments.

Distribution patterns of calcium-binding proteins in pancreatic tissue of non-diabetic as well as type 2 diabetic rats and in rat insulinoma beta-cells (INS-1).

The present study dealt with the localization of different calcium-binding proteins (CaBPs) in the pancreatic tissue of non-diabetic and diabetic rats and in rat insulinoma beta-cells (INS-1). Transcripts of CaBPs displayed different expression levels in rat pancreatic tissue and INS-1 cells. Immunohistochemistry demonstrated that three of these proteins, calmodulin, calreticulin and calbindin-D28k, were located predominantly in the pancreatic islets (in both alpha- and beta-cells) of rats, showing weaker labeling of exocrine tissue.

Loss of melatonin signalling and its impact on circadian rhythms in mouse organs regulating blood glucose.

The transmission of circadian rhythms is mediated by specific promoter sequences binding a particular circadian clock factor. The pineal hormone melatonin acts via G-protein-coupled receptors to synchronise these clock-generated circadian rhythms. The study was aimed to elucidate the possible role of melatonin as a zeitgeber for peripheral clocks in pancreas and liver.

Increased melatonin synthesis in pineal glands of rats in streptozotocin induced type 1 diabetes.

It is well-documented that melatonin influences insulin secretion. The effects are mediated by specific, high-affinity, pertussis-toxin-sensitive, G protein-coupled membrane receptors (MT(1) as well MT(2)), which are present in both the pancreatic tissue and islets of rats and humans, as well as in rat insulinoma cells (INS1). Via the Gi-protein-adenylatecyclase-3',5'-cyclic adenosine monophosphate (cAMP) and, possibly, the guanylatecyclase-cGMP pathways, melatonin decreases insulin secretion, whereas, by activating the Gq-protein-phospholipase C-IP(3) pathway, it has the opposite effect.

Melatonin stimulates inositol-1,4,5-trisphosphate and Ca2+ release from INS1 insulinoma cells.

The effects of melatonin in mammalian cells are exerted via specific receptors or are related to its free radical scavenging activity. It has previously been reported that melatonin inhibits insulin secretion in the pancreatic islets of the rat and in rat insulinoma INS1 cells via Gi-protein-coupled MT1 receptors and the cyclic adenosine 3',5'-monophosphate pathway. However, the inositol-1,4,5-trisphosphate (IP3) pathway is involved in the insulin secretory response as well, and the melatonin signal may play a part in its regulation.