THE REGULATION OF INSULIN ACTION IN ISOLATED ADIPOCYTES - ROLE OF THEPERIODICITY OF FOOD-INTAKE, TIME OF DAY AND MELATONIN

Isolated adipocytes from rats submitted to four weeks of ad libitum fe eding (AL) or meal feeding (MF, 2 h/22 h, feeding/fasting, meal time: 8:00-10:00 a.m.) schedules or pre-incubated with or without melatonin (0, 1 nM, 10 nM, 100 nM) for 5 h were submitted to insulin-stimulated [H-3]-2-deoxyglucose (0.1 mM, 0.12 muCi) uptake rate measurements and insulin binding assays. Insulin sensitivity was defined as the hormone concentration capable of producing the half-maximal transport rate. I nsulin sensitivity varied depending on the previous conditions of the adipocytes. In MF animals, adipose cells were more sensitive (EC50 = 0 .175 ng/ml) just at the moment of the expected meal. In AL rats, sensi tivity was lower (EC50 = 0.678 ng/ml) at 8:00 a.m. and increased (EC50 = 0.398 ng/ml) at 4:00 p.m. These data clearly implicate the expectat ion of food and period of the day with the regulation of insulin actio n. All these modifications in sensitivity occurred without any change in insulin receptor number or affinity. Melatonin, a secretory product of the pineal gland, induced an increase in cell sensitivity to insul in in adipocytes incubated with the highest hormone concentration (100 nM). We conclude that factors related to feeding training and circadi an rhythmicity modulate cell sensitivity to insulin.