608 



Ontogeny of Endocrine Correlation 



by an examination of the developmental 

 changes in blood sugar and liver glycogen 

 with the time that insulin secretory activity 

 of the beta cells is cytologically indicated. 



Although the causal relations between the 

 accumulation of carbohydi'ates in the blood 

 and liver and the histogenesis of the cell 

 types of the islets have not been explored on 

 a scale commenstirate with the importance 

 of this problem, some suggestive information 

 is available for examination. In the normal 

 chick embryo, Konigsberg ('54) finds by 

 quantitative microchemical methods that the 

 blood sugar rises from 87.1±:2.8 mg. per 

 cent on the eighth day to a level of 112±:5.5 

 per cent on the tenth day, remaining some- 

 what constant at this level until about the 

 fourteenth day. Following this plateau, the 

 blood sugar again rises to an average level 

 of 151.9±6.5 mg. per cent on the sixteenth 

 day. These findings are in general agreement 

 with those of Leibson and Leibson ('43) 

 with respect to the periods of increase and 

 the plateau in blood sugar level, save for 

 the additional point that the blood sugar 

 level apparently reaches a still higher peak 

 after the eighteenth day. Similar parallel 

 changes likewise take place in the amount 

 of liver glycogen. Initially present as traces 

 on the sixth day, the amount of liver glyco- 

 gen tends to increase gradually until the 

 ninth day, then declines, becoming most 

 marked on the twelfth day (Dalton, '37) — 

 according to Konigsberg changing from 3.90 

 ±0.62 per cent (dry weight) on the tenth 

 day to 2.32±:0.35 per cent on the twelfth 

 day, and to a value of 7.17±0.63 per cent 

 on the fourteenth day. Beginning on the 

 thirteenth day the glycogen content of the 

 liver rises rapidly to its highest value on 

 the nineteenth day and then appears to drop 

 precipitously at about the time of hatching 

 (Dalton, '37; Leibson, '50). It is significant 

 to note that immediately prior to the time 

 of onset of the second rise in carbohydrate 

 accumulation in the blood and liver a few 

 beta cells are first identified on the twelfth 

 day according to Villamil ('42). Whether 

 subsequently the number of beta cells in- 

 creases concomitantly with the rapid rise in 

 carbohydrates has not been worked out. 



In the albino rat fetus at relatively late 

 stages (ca. 16 days to term), according to 

 Corey ('32), the blood sugar increases quan- 

 titatively with advance in fetal age, more 

 or less gradually at first, followed by a period 

 of very rapid increase (20± day to term.) 

 This period of rapid increase coincides in 

 time not only with the initiation of beta cell 



differentiation and a most rapid increase in 

 their number, but also with a prominent 

 development of the capillary network within 

 the larger islets. A similar pattern of quan- 

 titative increase in liver glycogen is exhib- 

 ited in fetuses between the 16± day and 

 term (Corey, '35). 



By way of generalization, both blood sugar 

 and liver glycogen are definitely present in 

 measurable quantities at a time before beta 

 cells can be distingviished cytologically by 

 secretory granules and in the case of blood 

 sugar (probably present from the beginning 

 of vascular circulation) even before the islets 

 are formed. It is clear, therefore, that the 

 early accumulation of carbohydrate in the 

 blood and liver is independent of insulin 

 secretory activity of the islets. At later stages 

 in development, at about the time that the 

 rate of increase in blood sugar and liver 

 glycogen somewhat abruptly become mark- 

 edly accelerated, beta cell differentiation is 

 initiated. However, whether the striking cor- 

 respondence in time betw^een these events is 

 a true index of onset of insulin regulation 

 remains problematical. 



On the problem of the time in the course 

 of development that hormones of the anterior 

 pituitary and other endocrine glands be- 

 come interrelated with the functional ac- 

 tivity of the islets, the evidence is so scanty 

 as scarcely to permit consideration. Never- 

 theless, on the basis of considerable evidence 

 bearing on such interrelations in adult mam- 

 mals, it seems worth while to outline at 

 least briefly some of the specific kinds of 

 problems that challenge the embryologist. 



The current view that certain anterior 

 pituitary hormones act directly and/or in- 

 directly in exerting physiological effects 

 which are opposite to that of insulin poses 

 the problem as to when such opposing effects 

 arise in the course of development. In pitui- 

 taryless chick embryos (produced by removal 

 of the forebrain region at 33 to 38 hours) 

 profound changes from the normal occur 

 in (1) accumulation of carbohydrates in the 

 blood and liver, (2) the adrenal cortex, and 

 (3) the thyroid. The amount of blood sugar 

 is increased over normal values (see Fig. 213) 

 from the eighth to the thirteenth day, with 

 a drop on the fourteenth day; the amount 

 of liver glycogen increases from the tenth 

 to the fomteenth day (Konigsberg, '54).* 

 Furthermore, pituitary removal leads to sub- 

 normal activity of the thyroid and adrenal 



* Cf. Jost ('51a) for evidence that the quantity of 

 liver glycogen is markedly reduced after pituitary 

 removal (decapitation) in the rabbit fetus. 



