Introduction A network of transcription factors controls the differentiation of islet cells during pancreas organogenesis (for a review, see Cano et al . (2013) ). Neurog3 is central in this process as this gene is essential for determining the
Laure Nivlet, Joel Herrmann, Delia Esteban Martin, Aline Meunier, Christophe Orvain and Gérard Gradwohl
Nils Wierup, Frank Sundler and R Scott Heller
) made a corresponding description of B-cells of normal human pancreas. The granules of the B-cells are characterised by a dense core of crystalline structure in humans and round to ovoid in rodents, surrounded by an electron lucent halo between the
Riccarda Granata, Alessandra Baragli, Fabio Settanni, Francesca Scarlatti and Ezio Ghigo
tissues, including the gastrointestinal tract, pancreas, brain, pituitary gland, kidney, lung, heart, and placenta. Similarly, GHS-R1a is expressed in a variety of tissues (suggesting that AG may target them) besides the hypothalamus and pituitary ( Kojima
Sucharitha Iyer and Sunita K Agarwal
2009 Cellular functions of menin . In SuperMEN1 Pituitary, Parathyroid and Pancreas . pp 37–50. Eds. K Balogh & A Patocs. New York: Springer , New York, NY ( https://doi.org/10.1007/978-1-4419-1664-8 ) Huang J Gurung B Wan B Matkar S
Pierre Moulin, Yves Guiot, Jean-Christophe Jonas, Jacques Rahier, Olivier Devuyst and Jean-Claude Henquin
at the apical pole of epithelial cells in kidney ( Chambrey et al. 1998 ), intestine ( Chu et al. 2002 ) and duct cells of salivary glands and pancreas ( Lee et al. 1998 , 2000 ), where they play a role in Na + and fluid absorption, and
PS Leung and PO Carlsson
The classical concept of the renin-angiotensin system (RAS) is that of a blood-borne cascade, whose final and bioactive product, angiotensin II, plays an important endocrine role in the maintenance of blood pressure and electrolyte as well as fluid balance. In addition to this circulating RAS, there are an increasing number of studies to suggest the existence of a local angiotensin-generating system in several tissues. The so-called tissue RAS can act locally as a paracrine and/or autocrine factor in meeting specific needs for individual tissues and it can operate, in whole or in part, independently of the circulating counterpart. Recent studies on the expression and localization of key RAS components, particularly angiotensinogen and renin, have provided solid evidence for the existence of an intrinsic, angiotensin-generating system in the pancreas. The tissue RAS has a potential role in finely regulating exocrine and endocrine functions of the pancreas such as ductal anion secretion and islet hormonal secretion. Some of these effects may be exerted via the markedly vasoconstrictive effects of RAS. Of particular interest in this context are the recent epidemiological data showing that administration of angiotensin-converting enzyme inhibitors appears to be protective against the development of diabetes in hypertensive patients. Moreover, the upregulation of pancreatic RAS has been shown to occur during chronic hypoxia. The significance of changes in pancreatic RAS could have a potential role in acute pancreatitis, islet transplantation and in different shock states, by causing a further decrease of blood perfusion in the pancreas.
J Hogg, D J Hill and V K M Han
Insulin is important for optimal fetal and neonatal growth and development. Its continued availability is due, in part, to ongoing islet cell growth within the pancreas. IGFs and IGF-binding proteins (IGFBPs) have been implicated as paracrine regulators of islet cell growth within the developing pancreas. The purpose of this study was to determine whether the intact rat pancreas expresses mRNAs for IGF-I, IGF-II and IGFBPs, and how these might change with development. Liver was studied as a control tissue. Pancreas and liver were taken from fetal rats at 20–22 days of gestation, from postnatal rats at 1–21 days and from adult animals, and mRNAs for IGFs-I and -II and IGFBPs-1 to -6 were detected by Northern blot hybridization. The amount of IGF-II mRNA was greatest in the liver and pancreas of the fetal rat, and declined in both tissues during the neonatal period. Conversely, IGF-I mRNA levels were low but detectable in fetal life, and rose to adult levels within 2 weeks of birth. Both IGFBP-1 and IGFBP-2 mRNAs were present in fetal rat liver, increasing in amount over the first week of life, and declining in the adult. However, within the pancreas, IGFBP-1 mRNA was undetectable and IGFBP-2 mRNA was very low in the fetus and neonate. Both IGFBP-1 and IGFBP-2 mRNAs transiently appeared in the pancreas between postnatal weeks 2 and 3 and declined in the adult. IGFBP-3 and IGFBP-4 mRNAs were detected in both the liver and pancreas throughout the developmental period studied. IGFBP-3 mRNA increased in amount immediately following birth, while the quantity of IGFBP-4 mRNA increased sharply in liver from postnatal day 21, but declined in the pancreas. mRNA for IGFBP-5 or -6 was undetectable in either tissue.
The results show that both IGF-I and IGF-II are expressed by rat pancreas from at least 20 days of gestation, the latter being predominant in fetal life and the former during postnatal development. In addition, at least four IGFBP mRNAs (IGFBPs-1, -2, -3 and -4) were expressed within the pancreas with distinct developmental patterns. IGFBP-3 and -4 were predominant in the fetal and neonatal periods, while increased expression of IGFBPs-1 and -2 occurred 2–3 weeks after birth. The ontogeny of IGFBP mRNA expression in pancreas differed from that in liver. The temporal and spatially specific pattern of IGF and IGFBP gene expression within the developing pancreas supports a paracrine role for the IGF—IGFBP axis during pancreatic development in the rat.
SP Ip, TP Wong, SJ Tsai and PS Leung
Previous studies have shown that the expression of the major components from a local pancreatic renin-angiotensin system (RAS) was upregulated after chronic exposure to oxygen deprivation (10% oxygen). In the present study, the reversibility of expression for the pancreatic RAS affected by chronic hypoxia was investigated in the pancreas. Rats were first subject to hypoxia for one Month and they were then returned to normoxic conditions for a varying period of time (1, 2, 3 and 4 weeks). The degree of recovery in the expression of RAS components was analyzed with standard curve-quantitative competitive-reverse transcription-polymerase chain reaction (SC-QC-RT-PCR), Western blot analysis and a specific assay for angiotensin-converting enzyme (ACE) activity. Results from SC-QC-RT-PCR showed that the upregulated expression of angiotensin II type 1 (AT(1)) receptor mRNA following chronic hypoxia could be completely restored to the control level after the rats were returned to the normoxic condition for 3 weeks. The reversibility of mRNA expression for angiotensin II type 2 (AT(2)) receptor and angiotensinogen was observed after the return to normoxic conditions for 2 and 3 weeks respectively when compared with that of their respective controls. Results from Western blot analysis further confirmed that the expression of AT(1) receptor protein was also reversible after return to normoxic conditions for 4 weeks. In addition, the activation of ACE activity returned to its normal level in a time-dependent manner. These data indicate that the upregulation of a local pancreatic RAS affected by chronic hypoxia could be recoverable. The significance of its reversibility and adaptability following chronic hypoxia may be of physiological relevance to the pancreas.
E L Calvo, G Bernatchez, G Pelletier, J L Iovanna and J Morisset
Insulin-like growth factors (IGFs) are important peptides involved in the regulation of cell growth and differentiation in many tissues. The ontogeny of IGF-I was examined in pancreata from 19-day rat fetuses, newborns and 5-, 11-, 26- and 70-day-old rats. For the regeneration studies two models were used: (i) 90% pancreatectomy was carried out and the rats were killed at 1, 2, 3 and 6 days after resection; (ii) acute pancreatitis was induced with caerulein (12μg/body weight three times a day every 8 h for 2 days) and the rats were killed at 1, 2, 5, 7 and 9 days after the first injection. Total RNA was extracted by the guanidinium isothiocyanate method and Northern blots were performed using total RNA and labeled cRNA probes. Abundance of the different mRNA transcripts was estimated by densitometric scanning and normalized to the abundance of 18 S rRNA for each time point. Northern blot analysis during ontogeny showed four (0·8–1·2, 1·9, 4·7 and 7·5 kb) major transcripts in the rat pancreas and liver. Total IGF-I mRNA was 40-fold higher in the adult liver than in the adult pancreas. Moreover, in the liver, IGF-I mRNA levels were higher in the adult than in the fetus, whereas in the pancreas, the highest levels were observed around birth. During the first 3 days after pancreatectomy, a peak of maximal expression was observed after the second day. Densitometric analysis of each IGF-I mRNA species showed concomitant increases in all transcripts. After 6 days, all transcripts had returned to near-control values. IGF-I mRNA expression 2 days after pancreatectomy was 3·5-fold higher than in the newborn. During the first 2 days of acute pancreatitis induction, overexpression of IGF-I mRNA was observed. However, soon after the second day of caerulein treatment, the 7·5 kb transcripts remained elevated whereas those of the others regressed toward control values. Our results show that IGF-I mRNA is overexpressed in both models of pancreatic regeneration but downregulated in the normal adult pancreas.
Laura de Miguel-Santos, Elisa Fernández-Millán, María Ángeles Martín, Fernando Escrivá and Carmen Álvarez
Introduction It is generally accepted that the developing endocrine pancreas undergoes substantial remodeling during the neonatal period and that replication, neogenesis, and apoptosis play main roles in this process. In rodents, many of the β