The sand rat, when its diet is changed from pure vegetable to a mixed diet of vegetables and laboratory chow, often develops a diabetic syndrome, but may remain euglycemic or intermittently hyperglycemic. In the present study, insulin secretion by incubated pieces of pancreatic tissue from euglycemic and intermittently hyperglycemic animals fed a mixed diet was higher than that of control animals fed a pure vegetable diet. In the euglycemic and intermittently hyperglycemic rats, increased responsiveness of the pancreatic tissue to glucose, both in vitro and in vivo, was accompanied by morphologic signs of increased protein synthetic activity of the beta cells. Evidence of enlarged islets was often striking and beta cell degranulation was variable, so that the total insulin content of the pancreas remains generally normal or may be increased. In severely diabetic rats, the rate of insulin secretion induced by glucose in vitro was reduced; however, relative to the markedly reduced insulin content of the pancreas, a greater mobilization of the stored hormone is observed. The beta cells of these animals were filled with glycogen, and a reduction of the granular endoplasmic reticulum and other cell organelles was seen. It is suggested that the insufficient insulin supply and severe hyperglycemia at this stage of frank diabetes could be chiefly due to impaired insulin synthesis.

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