1. Investigación

Glucose and insulin relationship with aging were studied in fed rats. Levels of basal circulating glucose did not change while those of RIA-insulin increa!ed and RIA-glucagon decreased lincary with animal weight. The oral glucose tolerance test revealed a greater increase in blood glucose in adult and old rats than in prepubcrals, while the rise in plasma insulin was faster and greater in the oldest group. After intravenous glucose load, plasma insulin increase was greater in adult than in prepuberal and old rats, and in the latter group values remained elevated for a longer period. The hypoglycemic response to i.v. insulin was greatest in the prepuberals with no difference between adult and old rats. In prepuberals, the augmented insulin sensitivity was counteracted by retarded msulinotropic glucose action and an enhanced basal glucagon level, while in the old animals normoglycemia was maintained due to an augmented secretory response of B cells. counteracted by reduced sensitivity to endogenous insulin.

El ayuno de 48 h produjo en ratas, mantenidas en jaulas metabólicas, una disminución en la cantidad de agua bebida y aumento del volumen de orina excretada. Tanto la cantidad de creatinina como de urea excretada al dia disminuyeron con el ayuno, mientras que la de amoniaco aumentó. Ademas de demostrar la perdida de agua metabólica con el ayuno, los resultados indican que el principal producto de! catabolismo de aminoacidos con el ayuno es el amoniaco derivado del metabolismo de la glutamina en el riñón mas que la urea formada en el higado.

Suckling rats from 5 to 30 days of age were subjected to fasting in a 37° C chamber to avoid possible metabolic effects from low environmental temperature. The percentage of body weight loss in 24 h fasting increased along with the age of the rats. Blood glucose levels were the same in 5, 10, 20 and 30 day old animals when fed, whereas fasting produced a fall in all the groups which was minimal in the 20 day old animals. Plasma insulin levels were rather low in 10-day-old fed animals; the maximal decrease in this parameter was reached by 5-day-old rats under fasting. Both beta-hydroxybutyrate and acetoacetate levels were higher in animals of 5 and 1 0 days of age than in those of 30 days, but fasting did not produce any changes in the former while those parameters augmented in the 20 and 30-day-old animals. The results are discussed in relation to the high fat content in the mother's milk. which affects the metabolic situation of the suckling rats when fed and their response to the fasting situation.

The effect of glucose, arginine, pyruvate and palmitate administration on levels of circulating glucose and RIA-insulin was studied in fed and 48 h-fasted rats. The rise in blood glucose level after oral glucose load was greater in fasted than in fed rats, whereas plasma insulin level increase was similar in both groups. When glucose was given intravenously, plasma RIA-insulin rose only in the fed animals. Arginine administration produced minor changes in these parameters in both fed and fasted rats. Oral pyruvate produced greater enhancement in blood glucose concentration in fasted than in fed animals while plasma insulin levels rose only in the fed rats. After palmitate load, blood glucose levels increased only in the fed animals in which there was also an increase in plasma insulin levels following intravenous administration of fatty acid. These results suggest that none of the metabolites used except glucose has a physiological role in insulin secretion in the fed or fasted animals; in the latter group sensitivity to glucose stimulus was greatly reduced while the release of insulinotropic gastrointestinal factors after administration of oral glucose appeared less affected. The changes in blood glucose levels observed after addition of pyruvate or palmitate are discussed in terms of the role of pyruvate as a gluconeogenetic substrate and of the effect of palmitate on glucose metabolism.

Female rats were treated with two daily equihypoglycemic doses (as observed in acute treatment) of tolbutamide, glibenclamide or glipentide . by stomach tube, and were compared with control ammals treated with the suspending medium alone. On day 29 the rats were subjected to a 48 h fast and then were injected intraperitoneally with 100 .μMoles of C' -alanine. Blood samples were collected before and 5, 15 and 30 minutes after the alanine injection, at which time the animals were killed. Blood glucose levels increased after the injection of alanine in all groups, but at the different times stll:died, both the glibenclamide and glipentide treated_ anu_n~ls showed hypoglycemia versus controls. The rad10act1:"1ty found in blood glucose and liver glycogen and glycendeglycerol decreased in the glibenclamide treated anima~s compared with controls while in the other groups 1t was similar. The increase in liver glycogen after the injection of alanine was also diminished in the_ glibenclamide treated animals. Alanine produced an mcrease in the plasma levels of gluconeogenic, basic, aromatic and sulphur-containing amino acids in the controls, while in the animals treated with glipentide the alanine effect was less pronounced. The results show an impairment of gluconeogenic function in glibenclamide treated animals. The effects of both tolbutamide and glipentide were less dramatic. Nevertheless, the findings hinted at an effect of both drugs upon glycogen metabolism in liver.