The secretory response of rat islets of Langerhans was examined during pregnancy and compared with insulin release in normal rat islets. The threshold for a secretory response to glucose was lowered for islets from pregnant rats by comparison with non-pregnant controls. In addition, such islets showed a greatly increased sensitivity to glucose concentrations over the range 3\m=.\5-20 mmol/1. Significantly lower fasting blood glucose levels were found in pregnant rats in vivo, compared with controls.Insulin secretagogues other than glucose were tested for their effects on islets during pregnancy. Despite the high baseline of insulin secretion in response to glucose in pregnancy, there was an additional increased secretory response to arginine and theophylline. In contrast to their response to glucose, pregnant rat islets did not display an increased sensitivity to leucine. Glucagon, while it increased the insulin response of normal islets, had no significant effect on increasing the insulin response from pregnant rat islets suggesting that adenyl cyclase activity is already highly stimulated in pregnancy.In addition, the insulin, DNA and protein content of islets during pregnancy were increased significantly above normal values.The results suggested that rat islets are not only larger in pregnancy, but that they possess a more sensitive mechanism for detecting and responding to glucose and other secretagogues.
SUMMARY The effects of diet on the altered insulin secretory responses of islets of Langerhans of pregnant rats have been investigated. The daily food intake of pregnant rats was found to exceed that of control non-pregnant rats by 20% on average. Depriving pregnant rats of this additional food resulted in an alteration in the pattern of insulin secretion seen in pregnancy, such that the sensitivity to stimulation by low glucose concentrations was abolished. The contribution made by different components of the diet to the secretory response in pregnancy was investigated. When additional carbohydrate, though not protein, was fed to pregnant rats on a restricted food intake, the sensitivity of the islets to glucose stimulation was restored. It was concluded that the quantity and in particular the carbohydrate content of food eaten by pregnant rats exerts an important influence on the changes in insulin secretion in pregnancy.
Since porcine islets are considered a likely tissue source for islet transplantation we have studied the insulin secretory responses to stimuli and some of the cell surface antigen characteristics of porcine islet cells. In a static incubation system, the threshold level of glucose required for the stimulation of insulin secretion from freshly isolated porcine islets was found to be between 2.8 and 4.2 mmol glucose/l. Arginine (5 mmol/l) and 3-isobutyl-l-methylxanthine (1 mmol/l) potentiated insulin release induced by 8.3 mmol glucose/l. Leucine (5 mmol/l) initiated release in the presence of 2 mmol glucose/l. Neither beta-hydroxybutyrate (10 mmol/l) nor octanoate (5 mmol/l) potentiated insulin release induced by 8.3 mmol glucose/l, but beta-hydroxybutyrate initiated release in the presence of 2 mmol glucose/l while octanoate did not. A 125I-labelled protein A binding assay and an enzyme-linked immunosorbent assay system were used to detect antibody binding to islet and non-islet cells. Monoclonal antibodies raised against intact rat islets were shown to bind to both porcine and rat islet cells but not to rat hepatoma tissue culture cells or rat insulinoma cells. The serum from recently diagnosed type I diabetics was shown to bind to rat islet cells in a 125I-labelled protein A binding assay, while serum from control subjects showed little, if any, binding. Porcine islet cells were unable to distinguish between the sera of recently diagnosed type I diabetics and controls in a similar assay. In conclusion, porcine islets respond to many of the major insulin secretagogues to which human islets are sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)
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