Relationship between two stages of prandial insulin release in rats.

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Abstract
The preabsorptive plasma immunoreactive insulin (IRI) and blood glucose (BG) levels of rats with denervated .beta.-cells were compared with those of normal rats. Preparation of rats with selectively denervated .beta.-cells was accomplished by transplantation of fetal pancreases into diabetic rats. Postabsorptive immunoreactive insulin and blood glucose levels were determined in 5 groups of unrestrained but caged rats. Normal rats were offered glucose by either an oral or gastric route of administration. The same oral dose was also given to ventromedial hypothalamic (VMH) nucleus-lesioned, transplanted and vagotomized rats. The insulin response and blood glucose changes were also determined in normal rats subjected to an i.v. glucose infusion that duplicated the BG rise produced by the oral intake selected. All measurements were performed in animals allowed free movement in their home cages and offered a free oral glucose intake. After successful transplantation of fetal pancreases into diabetic rats, the orally mediated peak of preabsorptive insulin release was abolished, the 2nd preabsorptive peak, elicited at the gastrointestinal level, was maintained. The insulin release reflexly triggered by food-related stimuli at the oral level was caused by a direct vagal stimulation of the .beta.-cells, but the insulin release induced at the gastrointestinal level was under an indirect vagal influence. Possible mechanisms are discussed. The results confirm and quantify the difference noted in the insulin response to orally administered glucose and to i.v. administered glucose, adjusted to produce an equivalent peripheral BG rise. There is also a potentiation of the postabsorptive release, reflexly induced by food-related stimuli at both the oral and enteral levels. Insulin released before the intestinal absorption of nutrients facilitates and accelerates the postabsorptive glucose uptake. The role of the vagus nerve and of the VMH nuclei in this process is discussed.