Effect of conbined administration of counterregulatory hormones during insulin-induced hypoglycemia in rats: lipolysis mediated by a Beta-adrenergic mechanism contributes to hyperglycemia

The synergistic effect of combined injection of glucagon (G), cortisol (C) and phenylephrine + isoproterenol (E) during hypoglycemia in male adult Wistar rats was investigated. For this purpose we injected insulin (1 mg/kg), individually or combined (G+C, G+E, C+E and C+G+E). All drugs were injected ip and all rats were killed 60 min after insulin injection. The rise in glycemia with C+G+E was greater (delta = 107 mg/dl) than the sum of the responses to injection of C, G and E individually, or in double combination plus any single hormone injection. This synergistic effect was reproduced by G + C + isoproterenol (Iso) but not by G + C + phenylephrine (delta = 0 mg/dl). The results also showed a clear relationship between hyperglycemia and lipolysis. Thus, lipolysis mediated by a ß-adrenergic mechanism played a significant role in promoting hyperglycemia when Iso was combined with G and C

Neonatal monosodium glutamate treatment increases epididymal adipose tissue sensitivity to insulin in three-month old rats

We determined the response of glucose transport to insulin in isolated adipocytes and the lipogenic activity of insulin in fragments of epididymal adipose tissue obtained from male MSG-obese rats. Basal glucose transport rates (pmol 3 min-1 10(5) cells-1) were 100 higher in MSG than in control cells (3-month old male Wistar rats) pre-incubated for 30 min (P < 0.01). Nevertheless, when expressed as fmol 3 min-1 microns 2 cell surface area-1, transport rates were similar for the two groups (31.2 +/- 2.6 for MSG and 26.5 +/- 3.2 for controls, N = 7). No differences were observed in maximally insulin-stimulated glucose transport rates between groups (72.6 +/- 10.6 for MSG and 101.0 +/- 12.0 for controls, N = 7). In contrast, for adipocytes pre-incubated for 2 h, the basal uptake rates were 3.7 times higher and the maximal response to insulin was 103 higher in cells from MSG rats compared to control cells. These alterations in MSG rat adipocytes were accompanied by changes in cell sensitivity to insulin (EC50, 0.13 +/- 0.02 ng/ml for MSG vs 0.46 +/- 0.10 ng/ml for controls, P < 0.01). The rates of incorporation of labelled substrates (3H2O and 14C-glucose) into total lipids showed that in vitro lipogenesis was also 79 (3H2O) and 250 (14C-glucose) higher in MSG adipose tissue fragments. The MSG animals were consistently hyperinsulinemic. These data suggest that the obesity of 3-month old MSG rats is a metabolic alteration characterized by an enhanced adipocyte capacity to transport glucose and to synthetize lipids resulting in increased insulin sensitivity.

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

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: 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 [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 8:00 a.m. and increased (EC50 = 0.398 ng/ml) at 4:00 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.