Proteins synthesized and secreted during rat pancreatic development.

Abstract

The synthesis and secretion of proteins during development of the pancreas was analyzed using two-dimensional gel electrophoresis. The pattern of synthesis of the total proteins of the pancreas was found to change very little from 14 to 18 d gestation . In addition, the protein synthetic pattern of the embryonic pancreas was very similar to the protein patterns of several other embryonic tissues (gut, lung, and mesenchyme). Between 18 d gestation and the adult stage, the synthesis of the majority of protein species fades as the synthesis of the secretory (pro)enzymes becomes dominant . Thus, the terminal differentiation of the pancreas appears to involve the dominant expression of a limited set of genes (coding, in part, for the digestive [pro)enzymes) while the pattern of expression of the remaining domain remains relatively unchanged . Many of the secretory (pro)enzymes were identified and their synthesis during development was monitored . The synthesis of several secretory proteins was detected between 15 and 18 d gestation (e .g ., amylase and chymotrypsinogen), whereas the synthesis of others was not detected until after 18 d gestation (i .e ., trypsinogen, ribonuclease, proelastase, and lipase) . Between 18 d gestation and the adult stage, the synthesis of the digestive (pro)enzymes increases to >90% of pancreatic protein synthesis. The secretion of digestive (pro)enzymes was detected as early as 15 d gestation . The selective release of a second set of proteins was detected in the early embryo . These proteins are not detected in the adult pancreas or in zymogen granules but are also released by several other embryonic tissues. The function of this set of proteins is unknown .Pancreatic differentiation has been extensively studied at both morphological (18, 19) and biochemical levels (5,14,23,25). Normal development requires interaction between epithelial and mesenchymal tissues (8,25). Early investigations suggested that pancreatic differentiation is a multiphasic process (4, 21, 23) . In the rat, the formation of the pancreatic rudiment from the gut at -11 d gestation is coupled to the appearance of very low levels of exocrine proteins and insulin (the primary transition) . During the next 3-4 d, acinar structures form and the low levels of exocrine secretory proteins and insulin are maintained ("protodifferentiated state") (22, 23) . A second differentiative transition is detectable beginning at 14-15 d gestation when there is a rapid increase in rough endoplasmic reticulum, a 103-to 10'-fold increase in the accumulation of the specific exocrine enzymes and insulin, coupled with the appearance of zymogen granules in acinar cells and,8 granules in B cells (4,21,23) accumulate in a parallel fashion but slightly preceding the secretory proteins (10,11,20) .We have now used two-dimensional gel electrophoresis to monitor protein synthesis and secretion during development of the embryonic pancreas . This method allows analysis of both the pancreas-specific products (the secretory (projenzymes) and t...

Pancreas organogenesis: From bud to plexus to gland

“…The terminally differentiated acinar cell is a factory dedicated to synthesis, storage, and regulated release of approximately 24 digestive enzymes and accessory proteins. Mammalian acinar cells are packed with rough endoplasmic reticulum, have a huge and very active Golgi apparatus, an apical region dominated by zymogen granules, and a massive mitochondrial complement with prodigious energy potential (Padfield and Scheele, 1993;van Nest et al, 1980). In comparison to endocrine development, fewer transcription factors have been shown to be involved in acinar development.…”

Sdmg1 is a component of secretory granules in mouse secretory exocrine tissues

“…During secretory granule exocytosis, there appears to be little diffusion from the secretory granule membrane into the plasma membrane and, once the secretory granule cargo is expelled, the membrane of the secretory granule remains distinct from the plasma membrane and is eventually endocytosed and recycled (Thorn et al, 2004). Around 80 -90% of all protein secretion in the secretory exocrine cells of the pancreas and parotid salivary gland occurs through secretory granule exocytosis (Van Nest et al, 1980;von Zastrow and Castle, 1987); therefore, proteins involved in the regulated secretory pathway are expressed at high levels in these secretory exocrine cells (Wang et al, 2004(Wang et al, , 2007.…”

LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function

“…Within acini, the majority of the protein synthetic capacity is used to synthesize secretory proteins and is supported by more ribosomes than any other cell type in the body and by numerous mitochondria to provide energy (Harding et al 1977;Van Nest et al 1980). In response to the post-prandial hormones cholecystokinin (CCK), secretin, and gastrin, the mixture of enzymes and fluid that compose the pancreatic fluid is released via the pancreatic duct into the duodenum to facilitate digestion.…”