, excessive proliferation of ductal cells could block the passage of digestive enzymes secreted from the exocrine pancreas. Indeed, concerns about pancreatic inflammation were revealed following several case reports of pancreatitis in patients treated with
Benjamin J Lamont and Sofianos Andrikopoulos
C Chakraborty, S Sharma, N Katsumata, L J Murphy, I C Schroedter, M C Robertson, R P C Shiu, and H G Friesen
The secretion of peptide 23 by rat pituitary cells is stimulated by growth hormone-releasing hormone and inhibited by somatostatin. Recent cloning of the cognate cDNA for peptide 23 revealed that it is identical to pancreatitis-associated protein (PAP). In the present study, the clearance and tissue uptake of recombinant peptide 23/PAP in normal adult male rats was assessed. The plasma half-life of recombinant peptide 23/PAP was 4·8 ±1·4 (s.d.) min. Maximal accumulation of radiolabelled peptide 23/PAP was observed in the kidney, stomach, small intestine and pancreas whereas negligible uptake was seen in the liver, lung or heart. Peptide 23/PAP was detected in a variety of tissue extracts using a radioimmunoassay. Extracts of ileum contained the highest concentrations of peptide 23/PAP. In situ hybridization analysis showed that peptide 23/PAP mRNA was highly expressed in the columnar epithelial cells of ileum, jejunum and duodenum. These observations demonstrate that peptide 23/PAP, a protein previously thought to be of pituitary origin, is widely expressed in the gastrointestinal tract and that it is rapidly removed from the circulation by the kidney and by tissues which express peptide 23/PAP.
Journal of Endocrinology (1995) 145, 461–469
H Kayed, J Kleeff, S Keleg, MW Buchler, and H Friess
Indian hedgehog (IHH) and its receptors patched (PTC) and smoothened (SMO) belong to the hedgehog family of signaling molecules, which are essential for a variety of patterning events during mammalian tIssue development. IHH plays a role in pancreas organogenesis and differentiation, as well as in the regulation of insulin production. In the present study, the expression of IHH and its receptors was analyzed in normal human pancreatic and chronic pancreatitis (CP) tIssues using Northern blotting, immunohistochemistry and Western blotting, and was correlated with clinicopathological parameters. In addition, the effects of inhibition and stimulation of the hedgehog signaling pathway on cell growth were determined in TAKA-1 normal pancreatic ductal cells. IHH mRNA was expressed in the normal human pancreas and CP tIssues, with slightly higher expression levels in CP. Using immunohistochemistry, IHH and its receptors were localized mainly in the islet cells of the normal pancreas. In CP, IHH and its receptors were present in the cells forming tubular complexes and in the islets with a different signal pattern compared with the islets in the normal pancreas. Correlation between diabetic and non-diabetic CP patients revealed no significant difference in IHH, SMO, or PTC immunoreactivity. Inhibition of hedgehog signaling in TAKA-1 pancreatic ductal cells using cyclopamine significantly reduced their growth through cell cycle arrest, while stimulation of the IHH pathway enhanced the growth of these cells. In conclusion, IHH and its receptors are expressed in the normal human pancreas and in CP, yet with a different distribution and cellular localization. IHH signaling may be involved in the pathogenesis of CP, i.e. in the formation and proliferation of tubular complexes and in islet cell dysfunction.
S Yoshioka, S Fujii, JS Richards, and LL Espey
The ovulatory process in mammals involves gross physiological events in the ovary that cause transient deterioration of the ovarian connective tissue and rupture of the apical walls of mature follicles. This gonadotropin-induced process has features similar to an acute inflammatory reaction that affects most of the ovary. The present study reveals that the ovulatory events include induction of mRNA for pancreatitis-associated protein-III (PAP-III). Immature Wistar rats were primed with 10 IU equine chorionic gonadotropin s.c., and 48 h later the 12-h ovulatory process was initiated by 10 IU human chorionic gonadotropin (hCG) s.c. Ovarian RNA was extracted at 0, 2, 4, 8, 12 and 24 h after the animals were injected with hCG. The RNA extracts were used for RT-PCR differential display to detect PAP-III gene expression in the stimulated ovarian tissue. Northern blotting showed that transcription was significantly greater at 4-12 h after the ovaries had been stimulated by hCG. In situ hybridization indicated that PAP-III mRNA expression was limited mainly to the hilar region of the ovarian stroma, with most of the signal emanating from endothelial cells that lined the inner walls of blood vessels, and from small secondary follicles. Treatment of the animals with ovulation-blocking doses of indomethacin (an inhibitor of prostanoid synthesis) or epostane (an inhibitor of progesterone synthesis) revealed that ovarian transcription of PAP-III mRNA was moderately dependent on ovarian progesterone synthesis. In conclusion, the present evidence of an increase in PAP-III gene expression in gonadotropin-stimulated ovaries provides further evidence that the ovulatory process is comparable to an inflammatory reaction.
G Burnstock and I Novak
. 1985 , Laurent et al . 1999 ). Adenosine may be protective in pancreatitis (see below) and as indicated by the following experiments. Infusion of homocysteine, a risk factor for atherosclerosis, altered cholinergic endothelium-mediated vasodilation
Kook Hwan Kim and Myung-Shik Lee
toxin-induced injury. It remains to be determined whether FGF21 regulates activity and expression of the detoxification enzyme or whether this action exerts a protective effect against toxin-induced injury. FGF21 and pancreatitis It has been reported
Richard W Nelson and Claudia E Reusch
. Less severe changes involving the pancreatic islets and β-cells may predispose the adult dog to diabetes mellitus after the dog has been exposed to environmental factors, such as insulin-antagonistic diseases and drugs, and pancreatitis. The etiology of
Maria Petropavlovskaia, Julia Makhlin, John Sampalis, and Lawrence Rosenberg
proteins identified in rat, mouse, hamster, and humans and of a recently isolated human Reg4 protein, have not been well defined. These proteins expressed in various parts of the digestive system, have been associated with acute pancreatitis, inflammatory
E N Fazio, M Everest, R Colman, R Wang, and C L Pin
octapeptide (CCK-8) can help to regenerate exocrine tissue in cases of pancreatitis, but insulin is required for this regeneration as diabetic rats do not possess CCK-8-mediated regenerative ability. In these diabetic rats, administration of exogenous insulin
G M Ledda-Columbano, A Perra, M Pibiri, F Molotzu, and A Columbano
enzymes known to be released in the serum during pancreatitis, were determined. As shown in Table 1 , no increase in the activity of either of the enzymes was observed in T3-treated rats, the values being 184 U/l and 18 U/l for α-amylase and lipase