The regulation of insulin action in isolated adipocytes. Role of the periodicity of food intake, time of day and melatonin.

ABSTRACT

Isolated adipocytes from rats submitted to four weeks of ad libitum feeding (AL) or meal feeding (MF, 2 h/22 h, feeding/fasting, meal time 800-1000 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 [3H]-2-deoxyglucose (0.1 mM, 0.12 microCi) uptake rate measurements and insulin binding assays. Insulin sensitivity was defined as the hormone concentration capable of producing the half-maximal transport rate. Insulin 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, sensitivity was lower (EC50 = 0.678 ng/ml) at 800 a.m. and increased (EC50 = 0.398 ng/ml) at 400 p.m. These data clearly implicate the expectation of food and period of the day with the regulation of insulin action. 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 insulin in adipocytes incubated with the highest hormone concentration (100 nM). We conclude that factors related to feeding training and circadian rhythmicity modulate cell sensitivity to insulin.