Early exposure to a high-fat diet has more drastic consequences on metabolism compared with exposure during adulthood in rats.

The aim of this study was determine whether the introduction of a high-fat diet during the peripubertal phase induces significant changes in body weight control, glucose homeostasis and the parasympathetic tonus compared with the administration of this diet to adult rats. High-fat diet was offered to male Wistar rats at weaning or during adulthood. A group of rats received high-fat diet for 60 days, from weaning to 81-day-old (HF81) or from 60 to 120-day-old (HF120), whereas 2 other groups received a normal-fat diet (i. e., NF81 and NF120). We analyzed adiposity, glucose homeostasis, insulin sensitivity, and vagal nerve activity. High-fat diet increased the accumulation of adipose tissue in all of the rats, but the difference was greater in the rats that were fed the high-fat diet since weaning (p<0.001). The HF rats showed glucose intolerance with high levels of insulin secretion during the glucose tolerance test (p<0.01). Rats that were fed the high-fat diet presented severe insulin resistance, indicated by a low K itt (p<0.01). Interestingly, the HF81 rats exhibited greater insulin resistance compared with the HF120 rats (p<0.05). The recordings of vagus nerve activity showed that the HF rats had higher parasympathetic activity than the NF rats irrespective of age (p<0.01). Our results show that a high-fat diet offered to rats just after weaning or in adulthood both cause impairment of glycemic homeostasis and imbalance in parasympathetic activity. Importantly, the consumption of high-fat diet immediately after weaning has more drastic consequences compared with the consumption of the same diet during adulthood.

Transplantation of pancreatic islets from hypothalamic obese rats corrects hyperglycemia of diabetic rats.

Pancreatic islets isolated from adult obese rats, obtained by neonatal treatment with monosodium L-glutamate (MSG), oversecrete insulin stimulated by glucose concentration. Whereas adult MSG obese rats are hyperinsulinemic, their pancreatic islets still secrete insulin after high glucose demand. This is crucial so that the animals do not become hyperglycemic. Islets from MSG obese rats were implanted in diabetic donor rats so that the capacity of islets in regulating blood glucose concentration could be evaluated. Hyperglycemic (glucose 22 to 34 mmol/L) rats obtained with streptozotocin (STZ) treatment were used as recipients. Islet donors consisted of control adult and MSG obese rats. Only 600 islets were transplanted via the portal vein to diabetic rats. During 4 days after the transplant, fed blood glucose was monitored. After 12 hours of fasting the rats were killed; their blood samples were used to measure glucose and insulin concentration; retroperitoneal fat pads were isolated and weighed to estimate body fat. Transplanted islets from MSG obese rats decreased of fed glucose levels by 34% in diabetic rats (P < .05); however, glucose levels still remained twofold higher than those of intact controls (P < .05). Similar to MSG islets, islets grafts from control rats provoked the same effects in diabetic rats. High fasting blood glucose and low insulin levels of diabetic rats were corrected by islet grafts. Transplantations were able to recover 40% of fat in diabetic rats. The results demonstrated that islets from MSG obese rats may regulate blood glucose concentrations in diabetic rats, and suggesting that their function was not permanently altered by the onset of obesity.

Effects of decrease of extracellular sodium in carbachol-evoked catecholamine secretion in isolated adrenal medullae of rats.

The effect of extracellular Na(+) deprivation on the carbachol-evoked catecholamine secretion was evaluated in chromaffin cells. Isolated adrenal medullae of male Wistar rats were incubated in solutions with different sodium concentrations (144,0; 75,0; 25,0 and psi mM). Catecholamine secretions inversely increased as a response to fall of extracellular concentration of sodium. The magnitude of response to cholinergic stimulus (carbachol 100 microM) was decreased in low extracellular sodium concentration. Atropine (100 microM) inhibited secretion of catecholamine induced by carbachol in the presence and in the absence of extracellular sodium. Results suggest that in isolated adrenal medullae of rats (1) decrease in concentration of extracellular sodium increases secretion of catecholamines, perhaps by a greater influx of calcium from the extracellular environment through reversal of Na(+) /Ca(2+) exchanger; (2) intensity of catecholamine secretion induced by cholinergic stimulus seems to depend on extracellular sodium.

Insulin secretion and acetylcholinesterase activity in monosodium l-glutamate-induced obese mice.

OBJECTIVE: Pancreatic islets isolated from mice treated neonatally with monosodium L-glutamate (MSG) were used to study insulin secretion. MATERIALS AND METHODS: Total acetylcholinesterase (AchE) activity of tissue extract was measured as a cholinergic activity marker. Obesity recorded in 90-day-old MSG mice (OM) by Lee index reached 366.40 +/- 1.70, compared to control mice (CM) 324.40 +/- 1.10 (p < 0.0001). Glucose 5.6 mM induced insulin secretion of 36 +/- 5 pg/15 min from islets of CM and 86 +/- 13 from OM (p < 0.001). When glucose was raised to 16.7 mM, islets from OM secreted 1,271 +/- 215 and 1,017 +/- 112 pg/30 min to CM. AchE activity of pancreas from OM was 0.64 +/- 0.02 nmol of substrate hydrolyzed/min/mg of tissue and 0.52 +/- 0.01 to CM (p < 0.0001). Liver of obese animals also presented increase of AchE activity. RESULTS: These indicate that OM insulin oversecretion in low glucose may be attributed, at least in part, to an enhancement of parasympathetic tonus.

Low protein diets administered to lactating rats affect in a time-dependent manner the development of young.

The effects of diets with different protein levels were evaluated when given at different intervals to lactating rats. Food intake by the litter and weight gain by the young are investigated. From the time of birth, groups of five litters were fed with commercial diet (23% protein) or with semi-synthetic diets (4,8,12 and 16% protein) during the 1st, 1st and 2nd, or 1st, 2nd and 3rd weeks of lactation. After weaning, the young of dams, which were fed hypoprotein diets (4 and 8%), showed less food intake capacity, reduced growth capacity and, in adult life, low body weight in comparison to animals raised on commercial ration with higher protein contents. 12 and 16% protein diets did not cause any change in feeding behavior or in weight development as opposed to the 4 and 8% protein diets. Results suggest that the effects of early undernourishment are time-dependent and may cause irreversible changes in the regulation of metabolism and pathogenesis.

Glucose does not affect catecholamine stimulus-secretion coupling in rat adrenal medulla: relationship to low changes in osmolarity and to insulin.

Glucose levels were analyzed to see whether they directly affect the catecholamine release from chromaffin cells. We incubated isolated adrenal medullae of rats in Krebs-Hepes modified solutions with several glucose concentration, in the presence and absence of carbachol or insulin. Transfer of the medulla from a solution with 11.1 mM of glucose to a 0.56 mM one caused an increase in catecholamine secretion. Relative increase in change of glucose levels from 25 to 0.56 mM and from 50 to 0.56 mM enhanced the effect mentioned above. An inhibitory effect was detected after transfer of the medulla from 0.56 mM to 50 mM glucose. However, correction of solution osmolarity with mannitol or NaCl switched back catecholamine secretion to basal levels in all groups, and correction of solution osmolarity with sucrose indicated an impairment of catecholamine release. No difference was observed in stimulated catecholamine secretion (100 microM of carbachol) at all glucose levels. Further, the presence of insulin did not affect catecholamine secretion in all groups. Our results suggest that in isolated adrenal medullae of rats (1) glucose or variations in glucose levels do not affect catecholamine released; (2) isolated adrenal medulla of rat was highly sensitive to hyperosmolarity and extremely sensitive to hyposmolarity; (3) Insulin had no acute direct effect on catecholamine secretion in isolated adrenal medullae of rats.

Insulin secretion impairment and insulin sensitivity improvement in adult rats undernourished during early lactation.

In order to study the effect of undernutrition on the onset of disturbances in insulin secretion and insulin resistance, we compared the effects of a low protein diet containing 4% of protein (LPD) and a normal diet containing 25% of protein (NPD) supplied to the dams during the first 10 days of lactation when the pups turn into adults (90 days). We studies, in these rats, the insulin secretion, the glucose tolerance test (GTT) and, using the glucose clamp technique, the insulin resistance. The GTT showed a delay of the response of LPD group to the glucose challenge (1 mg/kg body weight) at 10 minutes (NPD = 450 +/- 27 mg/dl; LPD = 650 +/- 32 mg/dl, p < 0.01). The insulin secretion, four minutes after stimulation was found reduced in the LPD group (LPD = 1.1 +/- 0.08 microU/islet/min; NPD = 1.85 +/- 0.02 microU/islet/min, p < 0.01). Using the glucose clamp technique the plasma glucose concentration was raised during the first 20 minutes after the glucose stimulation with 10 mg/Kg-1.min-1 (NPD = 200 +/- 32 mg/dl and; LPD = 160 +/- 14 mg/dl., p < 0.01). Afterwards, the hyperglycemia was subsequently maintained (NPD = 154 +/- 9 mg/dl; LPD = 149 +/- 12 mg/dl) and the insulinemia was unchanged by infusion of glucose in the LPD group. In a similar experiment, the administration of glucose (10 mg/Kg-1. min-1) plus insulin (1.67 mU/Kg-1. min-1), the LPD group when compared with the NPD group, displayed an accentuated decreasing of glucose concentration level (LPD = 90 +/- 7 mg/dl; NPD = 130 +/- mg/dl., p < 0.01), 30 minutes after the infusion. The data suggest that undernutrition induces an adaptive process of insulin sensitivity which occurs together with an insulin secretion first phase blockage.