C. H. BEST 



of the pancreas in many instances of human diabetes. On the other 

 hand, there is no convincing proof that the islet cells are really normal 

 in these cases; and many investigators feel that the burden of proof 

 that the pancreas is not primarily or secondarily involved rests with 

 those who make this assertion. Careful estimations of the insulin 

 content of pancreas, if it were possible to do this under reasonably 

 standard conditions in autopsies on diabetics, would yield valuable 

 results. It is obvious, however, that the opportunities to make this 

 study in uncomplicated cases will be rare. The administration of 

 insulin or fasting will lower the insulin content of the pancreas in 

 normal animals, a point which must be considered when insulin 

 estimations are made. 



In experimental animals, permanent diabetes can be produced 

 by three procedures: by pancreatectomy, by destruction of the islet 

 tissue by the diabetogenic material of the anterior pituitary gland, and 

 by the administration of alloxan. All three methods effect removal 

 or practically complete destruction of the beta cells of the islands of 

 Langerhans. Substances are, however, present in the anterior 

 pituitary gland which aggravate diabetes in the completely depan- 

 creatized organism. A part of this effect appears to be due to a 

 deficient carbohydrate utilization in peripheral tissues. 



Apart from the possibility of developmental defects in islet 

 structure which would presumably appear in very young children and 

 the well-established arteriosclerotic changes in the pancreas of older 

 individuals, there is little real evidence on which a reasonable theory 

 of the etiology of diabetes may be supported. The association of the 

 diabetic state with overactivity of the anterior pituitary lobe of the 

 pituitary, as in the acromegalic, encourages further study along a 

 path which has already been well outlined. We must develop accurate 

 procedures for the assay of the diabetogenic materials in blood. It 

 has recently been shown that diabetes may be most favorably affected 

 by removal of the exciting cause which, in a few clinical cases, has 

 been found in one of the adrenal glands. Extracts containing the 

 hormones of the cortex of the adrenal may produce diabetes in the 

 partially depancreatized animal, and it is well established that, under 

 certain conditions, removal of the adrenal cortices ameliorates the 

 diabetic state caused by pancreatectomy in much the same way as 

 does removal of the anterior lobe of the pituitary. 



