EFFECTS OF LONG TERM ADMINISTRATION OF GLUCAGON ON THE PANCREATIC ISLET TISSUE OF RATS AND GUINEA-PIGS

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Abstract
Rats and guinea-pigs were injected every eight hours with crystalline glucagon (0.3-0.6 mg/kg) and killed after different periods of treatment up to 30 days. Immature animals (glucagon treatment commenced on the second postnatal day) were also included among the rats investigated. While the immature glucagon treated rats grew almost as well as their litter mate controls, there was a marked reduction of the body and adrenal weights, when the injections were started at a more adult age. In the latter rats the total islet volume was significantly reduced and the A1/A2 cell number ratio increased from 0.24 [plus or minus] 0.02 to 0.32 [plus or minus]0.02. In the guinea-pigs the glucagon treatment resulted in a considerable decrease in both the body and pancreatic weights. These changes were associated with a significant increase in the relative amount of the endocrine pancreas, the total islet volume being unchanged. While the A1 cells appeared unaffected by the glucagon treatment, the A2 cells were markedly atrophied. After an apparent initial increase there was a subsequent progressive diminution of the silvery-white dark field granulation of the A2 cells during the glucagon treatment. The postcoupled benzylidene reaction for tryptophane also decreased and became insignificant in guinea-pigs injected with glucagon for a long period. In the latter animals the percentage of A2 cells was only 3.4 [plus or minus] 0.2 as compared with 24.4 [plus or minus] 1.3 for the controls. As a consequence of this, the A1/A2 cell number ratio was about 6 times as high in the glucagon treated guinea-pigs. The data obtained for the longer term adaptation of the islets of Langerhans to the administration of glucagon support the concept that this hormone is secreted by the silver-negative A2 cells.