606 



Ontogeny of Endocrine Correlation 



the growth process is independent of cir- 

 culating hormones, the growth-regulating 

 hormones gradually take over via the sys- 

 temic circulation the function of coordi- 

 nating and regulating in final size and form 

 the expression of the intrinsic growth pattern 

 of the developing organism and its parts. To 

 paraphrase a passage of D'Arcy Thompson 

 ('42, p. 264), hormonal regulation of growth 

 processes is neither simple nor specific, but 

 implies a far-reaching and complicated in- 

 fluence on metabolism of already established 

 growth patterns of the developing body and 

 its parts. The actual growth expression is also 

 dependent upon environmental factors, since 

 nutrients, oxygen supply, temperature, etc. 

 have an effect on the physicochemical back- 

 ground in which the synthetic processes of 

 growth take place. 



ISLETS OF LANGERHANS 



Concerning the problem of the develop- 

 ment of functional activity of the endocrine 

 portion of the pancreas, the islets of Langer- 

 hans, little or no precise information is 

 available. Nevertheless, an attempt will be 

 made in this section to direct attention to 

 and to analyze so far as the evidence permits 

 such major problems as (a) the initiation of 

 insulin production and (b) the unfolding of 

 mechanisms of regulation of insulin secretion 

 into the blood circulation. (See Table 27.) 



MORPHOGENESIS, CYTOGENESIS, AND 



INITIATION OF INSULIN 



PRODUCTION 



As a basis for a proper imderstanding of 

 the functional development of the islets, it 

 is first of all essential to examine the normal 

 course of morphogenesis of the islet tissue 

 and the cytogenesis of the cell types. The 

 sequential steps in these processes have been 

 especially well worked out for the fetal and 

 early postnatal stages of the albino rat by 

 Hard ('44). Generally speaking, the islets 

 originate as cellular outgrowths from the 

 epithelium of the dorsal and ventral pan- 

 creatic lobes during their union and trans- 

 formation into the branching system of ducts 

 and terminal acini, which comprise the 

 exocrine glandular portion of the pancreas. 

 A very few islets are first identified as 

 offsets from the solid dorsal and ventral 

 lobes, respectively, on the thirteenth and 

 fourteenth days of gestation. The majority 

 of embryonic islets, however, are set off from 

 the epithelium of the primitive pancreatic 



tubules (formed by a rearrangement of cells 

 of the coalescing pancreatic lobes), which 

 are the progenitors of series of repeated units 

 of exocrine ducts, ductules, and acini. Such 

 islets, which are first apparent on the fif- 

 teenth day, increase rapidly in number and 

 in size with advance in fetal age, becoming 

 most marked in an 18-day fetus. During the 

 first week of postnatal life a very active 

 formation of new islets occurs. The majority 

 of these arise from the terminal portions of 

 the ducts at the bases of the acini.* It is of 

 interest to note that the potency for islet 

 formation, although present during the en- 

 tire course of morphogenesis of the exocrine 

 gland, tends to shift progressively to the 

 more terminal portions of the ducts as they 

 arise. 



With respect to the sequence of differen- 

 tiation of the islet cell types, the beta cell, 

 generally accepted as the source of insulin 

 in adult animals, is the only cell type to 

 arise during fetal life of the rat. The alpha 

 cell does not appear until the second day 

 after birth. The so-called delta cell (inter- 

 preted by some as a stem cell) has not been 

 identified during the developmental stages 

 under consideration. 



The beta cell is first identified in the 



* The apparent sequential development of two 

 main groups of islets in the rat seems to be in gen- 

 eral agreement with the older findings on several 

 mammalian species (for review, see Bargmann, 

 '39). According to the older investigators the first 

 group of islets, the so-called islets of Laguesse, de- 

 generate and disappear, while the second group is 

 retained as the definitive islets of Langerhans. The 

 validity of this view may be questioned on the basis 

 of the difficulty in distinguishing the islets as to 

 their exact source of origin and in following their 

 subsequent fate. Moreover, in the rat, although 

 there is a sequence in generation of islet tissue, the 

 set of embryonic islets persists into the postnatal 

 period and apparently differs in no essential partic- 

 ular from the second group except as to position of 

 origin. Similarly, in the development of the chick a 

 sequence in the generation of islets has been de- 

 scribed by Potvin and Aron ('27), the transitory 

 islets appearing at 8 days of incubation, the defini- 

 tive islets two days later. A more recent investiga- 

 tion by Villamil ('42), however, indicates that the 

 pattern of islet formation in the chick is actually 

 more complex, in that two types of islets — the so- 

 called "light" and "dark" islets — are simultane- 

 ously present on the eighth day. These islets exhibit 

 a differential behavior from the beginning. The 

 dark islets give rise to alpha and delta cells begin- 

 ning, respectively, on the eighth and fourteenth 

 days, whereas the light islets begin on the twelfth 

 day either to degenerate or to give rise to cells 

 with beta granules. The ultimate fates of these two 

 kinds of islets need to be worked out. 



