The pancreas is an organ containing two distinct populations of cells, the exocrine cells that secrete enzymes into the digestive tract, and the endocrine cells that secrete hormones into the bloodstream. It arises from the endoderm as a dorsal and a ventral bud which fuse together to form the single organ. Mammals, birds, reptiles and amphibians have a pancreas with similar histology and mode of development, while in some fish, the islet cells are segregated as Brockmann bodies. Invertebrates do not have a pancreas, but comparable endocrine cells may be found in the gut or the brain. The early pancreatic bud shows uniform expression of the homeobox gene IPF-1 (also known as IDX-1, STF-1 or PDX), which when mutated to inactivity leads to total absence of the organ. The occurrence of heterotopic pancreas in the embryo, and also the metaplasias that can be displayed by a regenerating pancreas in the adult, both suggest that only a few gene products distinguish the pancreatic cell state from that of the surrounding tissues of duodenum, gall bladder and liver. In the developing pancreatic buds, the endocrine cells start to differentiate before the exocrine cells, and co-expression of different hormones by the same cell is often observed at early stages. Although pancreatic endocrine cells produce many gene products also characteristic of neurons, evidence from in vitro cultures and from quailchick grafts shows that they are of endogenous and not of neural crest origin. Observational studies suggest strongly that both endocrine and exocrine cells arise from the same endodermal rudiment. Development of the pancreas in embryonic life requires a trophic stimulus from the associated mesenchyme. In postnatal life, all cell types in the pancreas continue to grow. Destruction of acinar tissue by duct ligation or ethionine treatment is followed by rapid regeneration. Surgical removal of parts of the pancreas is followed by moderate but incomplete regeneration of both acini and islets. Poisoning with alloxan or streptozotocin can lead to permanent depletion of beta cells. Although the cell kinetics of the pancreas are not understood, it seems likely that there is a continuous slow turnover of cells, fed from a stem cells population in the ducts, and that the controls on the production rate of each cell type are local rather than systemic.

Reference

Alpert
S.
,
Hanahan
D.
,
Teitelman
G.
(
1988
)
Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons.
Cell,
53
,
295
308
Andrew
A.
(
1976
)
An experimental investigation into the possible neural crest origin of pancreatic APUD (islet) cells.
J. Embryol. Exp. Morph
35
,
577
593
Bonner-Weir
S.
,
Trent
D. F.
,
Honey
R. N.
,
Weir
G. C.
(
1981
)
Responses of neonatal rat islets to streptozotocin.
Diabetes
30
,
64
69
Branch
C. D.
,
Gross
R. E.
(
1935
)
Aberrant pancreatic tissue in the gastrointestinal tract.
Arch. Surg
31
,
200
224
Brockenbrough
J.
,
Weir
G. C.
,
Bonner-Weir
S.
(
1988
)
Discordance of exocrine and endocrine growth after 90% pancreatectomy in rats.
Diabetes
37
,
232
236
Brosky
G.
,
Logothetopoulos
J.
(
1969
)
Streptozotocin diabetes in the mouse and the guinea pig.
Diabetes
18
,
606
611
De Castro Barbosa
J. J.
,
Dockerty
M. B.
,
Waugh
J. M.
(
1946
)
Pancreatic heterotopia.
Surg. Gyn. Obs
82
,
527
542
Deltour
L.
,
Leduque
P.
,
Blume
N.
,
Madsen
O.
,
Dubois
P.
,
Jami
J.
,
Bucchine
D.
(
1993
)
Differential expression of the two non-allelic proinsulin genes in the developing mouse embryo.
Proc. Natl. Acad. Sci. USA
90
,
527
531
Deltour
L.
,
Leduque
P.
,
Paldi
A.
,
Ripoche
M. A.
,
Dubois
P.
,
Jami
J.
(
1991
)
Polyclonal origin of pancreatic islets in aggregation mouse chimaeras.
Development
112
,
1115
1121
Devaskar
S. U.
,
Singh
B. S.
,
Carnaghi
L. R.
,
Rajakumar
P. A.
,
Giddings
S. J.
(
1993
)
Insulin-II gene expression in rat central nervous system.
Regulatory Peptides
48
,
55
63
Edwards
B. J.
,
Morley
J. E.
(
1992
)
Amylin.
Life Sci
51
,
1899
1912
Elsässer
H. P.
,
Biederbick
A.
,
Kern
H. F.
(
1994
)
Growth of rat pancreatic acinar cells quantitated with a monoclonal antibody against the proliferating cell nuclear antigen.
Cell Tissue Res
276
,
603
609
Fisher
N. F.
(
1924
)
Regeneration of the pancreas from the pancreatic duct.
J. Am. Med. Assoc
83
,
502
503
Fitzgerald
P. J.
,
Carol
B. M.
,
Rosenstock
L.
(
1966
)
Pancreatic acinar cell regeneration.
Nature
212
,
594
596
Friedmann
N. B.
,
Marble
A.
(
1941
)
Island hyperplasia in the partially depancreatized rat.
Endocrinology
29
,
577
582
Giddings
S. J.
,
King
C. D.
,
Harman
K. W.
,
Carnaghi
L. R.
(
1994
)
Allele specific inactivation of insulin 1 and 2, in the mouse yolk sac, indicates imprinting.
Nature Genetics
6
,
310
313
Githens
S.
(
1988
)
The pancreatic duct cell: proliferative capabilities, specific characteristics, metaplasia, isolation and culture. J. Pediat. Gastroenterol.
Nutrition
7
,
486
506
Gittes
G. K.
,
Rutter
W. J.
(
1992
)
Onset of cell-specific gene expression in the developing mouse pancreas.
Proc. Natl. Acad. Sci. USA
89
,
1128
1132
Grauer
T. P.
(
1926
)
Regeneration in the pancreas of the rabbit.
Am. J. Anat
38
,
233
253
Gu
D.
,
Lee
M. S.
,
Krahl
T.
,
Sarvetnick
N.
(
1994
)
Transitional cells in the regenerating pancreas.
Development
120
,
1873
1881
Gu
D.
,
Sarvetnick
N.
(
1993
)
Epithelial cell proliferation and islet neogenesis in IFNtransgenic mice.
Development
118
,
33
46
Guz
Y.
,
Montminy
M. R.
,
Stein
R.
,
Leonard
J.
,
Gamer
L. W.
,
Wright
C. V. E.
,
Teitelman
G.
(
1995
)
Expression of murine STF-1, a putative insulin gene transcription factor, incells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny.
Development
121
,
11
18
Hamming
N. A.
,
Reynolds
W. A.
(
1977
)
DNA synthesis in pancreatic islet and acinar cells in rats with streptozotocin induced diabetes.
Horm. Metab. Res
9
,
114
116
Herrera
P. L.
,
Huarte
J.
,
Sanvito
F.
,
Meda
P.
,
Orci
L.
,
Vassalli
J. D.
(
1991
)
Embryogenesis of the murine endocrine pancreas; early expression of pancreatic polypeptide gene.
Development
113
,
1257
1265
Herrera
P. L.
,
Huarte
J.
,
Zuffery
R.
,
Nichols
A.
,
Mermillod
B.
,
Philippe
J.
,
Muniesa
P.
,
Sanvito
F.
,
Orci
L.
,
Vassalli
J. D.
(
1994
)
Ablation of islet endocrine cells by targeted expression of hormone promoter-driven toxigenes.
Proc. Natl. Acad. Sci. USA
91
,
12999
13003
Hughes
H.
(
1956
)
An experimental study of regeneration in the islets of Langerhans with reference to the theory of balance.
Acta Anatomica
27
,
1
61
Jhappan
C.
,
Stahle
C.
,
Harkins
R. N.
,
Fausto
N.
,
Smith
G. H.
,
Merlino
G. T.
(
1990
)
TGFoverexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas.
Cell
61
,
1137
1146
Jonsson
J.
,
Carlsson
L.
,
Edlund
T.
,
Edlund
H.
(
1994
)
Insulin promoter-factor 1 is required for pancreas development in mice.
Nature
371
,
606
609
Kaung
H. L. C.
(
1994
)
Growth dynamics of pancreatic islet cell populations during fetal and neonatal development of the rat.
Dev. Dyn
200
,
163
175
Kruse
F.
,
Rose
S. D.
,
Swift
G. H.
,
Hammer
R. E.
,
MacDonald
R. J.
(
1993
)
An endocrine-specific element is an integral component of an exocrine-specific pancreatic enhancer.
Genes Dev
7
,
774
786
Le Douarin
N. M.
(
1988
)
On the origin of pancreatic endocrine cells.
Cell
53
,
169
171
Le Douarin
N. M.
,
Teillet
M. A.
(
1973
)
The migration of neural crest cells to the wall of the digestive tract in avian embryos.
J. Embryol. Exp. Morph
30
,
31
48
Lehv
M.
,
Fitzgerald
P. J.
(
1968
)
Pancreatic acinar cell regeneration IV. Regeneration after surgical resection.
Am. J. Pathol
53
,
513
535
Lienhard
G. E.
(
1994
)
Life without the IRS.
Nature
372
,
128
129
McEvoy
R. C.
(
1981
)
Changes in the volumes of the A-, B-and D-cell populations in the pancreatic islets during the postnatal development of the rat.
Diabetes
30
,
813
817
Miller
C. P.
,
McGehee
R. E.
,
Habener
J. F.
(
1994
)
IDX-1: a new homeodomain transcription factor expressed in rat pancreatic islets and duodenum that transactivates the somatostatin gene.
EMBO J
13
,
1145
1156
Monaghan
A. P.
,
Kaestner
K. H.
,
Grau
E.
,
Schutz
G.
(
1993
)
Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3, andgenes in determination of the definitive endoderm, chordamesoderm and neurectoderm.
Development
119
,
567
578
Muller
R.
,
Laucke
R.
,
Trimper
B.
,
Cossel
L.
(
1990
)
Pancreatic cell proliferation in normal rats studied by in vivo autoradiography with 3H-thymidine.
Virchows Arch. B
59
,
133
136
Nielsen
F. C.
(
1992
)
The molecular and cellular biology of insulin like growth factor II.
Prog. Growth Factor Res
4
,
257
290
Ohlsson
H.
,
Karlsson
K.
,
Edlund
T.
(
1993
)
IPF-1, a homeodomain-containing transactivator of the insulin gene.
EMBO J
12
,
4251
4259
Oliver
G.
,
Sosa-Pineda
B.
,
Geisendorf
S.
,
Spana
E. P.
,
Doe
C. Q.
,
Gruss
P.
(
1993
)
Prox 1, a prospero-related homeobox gene expressed during mouse development.
Mech. Dev
44
,
3
16
Palmiter
R. D.
,
Behringer
R. R.
,
Quaife
C. J.
,
Maxwell
F.
,
Maxwell
I. H.
,
Brinster
R. L.
(
1987
)
Cell lineage ablation in transgenic mice by cell specific expression of a toxin gene.
Cell
50
,
435
443
Pictet
R. L.
,
Clarke
W. R.
,
Williams
R. H.
,
Rutter
W. J.
(
1972
)
An ultrastructural analysis of the developing embryonic pancreas.
Dev. Biol
29
,
436
467
Raju
K.
,
Tang
S.
,
Dube
I. D.
,
Kamel-Reid
S.
,
Bryce
D. M.
,
Breitman
M. L.
(
1993
)
Characterization and developmental expression of Tlx-1, the murine homolog of HOX11.
Mech. Dev
44
,
51
64
Rao
M. S.
,
Dwivedi
R. S.
,
Yeldandi
A. V.
,
Subbarao
V.
,
Tan
X.
,
Usman
M. I.
,
Thangada
S.
,
Nemali
M. R.
,
Kumar
S.
,
Scarpelli
D. G.
,
Reddy
J. K.
(
1989
)
Role of periductal and ductular epithelial cells of the adult rat pancreas in pancreatic hepatocyte lineage.
Am. J. Pathol
134
,
1069
1086
Rink
T. J.
,
Beaumont
K.
,
Koda
J.
,
Young
A.
(
1993
)
Structure and biology of amylin.
Trends Pharmacol. Sci
14
,
113
118
Ronzio
R. A.
,
Rutter
W. J.
(
1973
)
Effects of a partially purified factor from chick embryos on macromolecular synthesis of embryonic pancreatic epithelia.
Dev. Biol
30
,
307
320
Rosenberg
L.
,
Brown
R. A.
,
Duguid
W. P.
(
1983
)
A new approach to the induction of duct epithelial hyperplasia and nesidioblastosis by cellophane wrapping of the hamster pancreas.
J. Surg. Res
35
,
63
72
Sandgren
E. P.
,
Luettke
N. C.
,
Palmiter
R. D.
,
Brinster
R. L.
,
Lee
D. C.
(
1990
)
Overexpression of TGFin transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia and carcinoma of the breast.
Cell
61
,
1121
1135
Sanvito
F.
,
Herrera
P. L.
,
Huarte
J.
,
Nichols
A.
,
Montesano
R.
,
Orci
L.
,
Vassalli
J. D.
(
1994
)
TGF-1 influences the relative development of the exocrine and endocrine pancreas in vitro.
Development
120
,
3451
3462
Scarpelli
D. G.
,
Rao
M. S.
(
1981
)
Differentiation of regenerating pancreatic cells into hepatocyte like cells.
Proc. Natl. Acad. Sci. USA
78
,
2577
2581
Shaw
J. W.
,
Latimer
E. O.
(
1926
)
Regeneration of pancreatic tissue from the transplanted pancreatic duct in the dog.
Am. J. Physiol
76
,
49
53
Siddle
K.
(
1992
)
The insulin receptor and type I IGF receptor: comparison of structure and function.
Prog. Growth Factor Res
4
,
301
320
Spooner
B. S.
,
Walther
B. T.
,
Rutter
W. J.
(
1970
)
The development of the dorsal and ventral mammalian pancreas in vivo and in vitro.
J. Cell Biol
47
,
235
246
Steiner
H.
,
Oelz
O.
,
Zahnd
G.
,
Froesch
E. R.
(
1970
)
Studies on islet cell regeneration, hyperplasia and intrainsular cellular interactions in long lasting streptozotocin diabetes in the rat.
Diabetologia
6
,
558
564
Teitelman
G.
(
1990
)
Insulin cells of the pancreas extend neurites but do not arise from the neurectoderm.
Dev. Biol
142
,
368
379
Teitelman
G.
,
Lee
J. K.
(
1987
)
Cell lineage analysis of pancreatic islet cell development: glucagon and insulin cells arise from catecholaminergic precursors present in the pancreatic ducts.
Dev. Biol
121
,
454
466
Teitelman
G.
,
Alpert
S.
,
Polak
J. M.
,
Martinez
A.
,
Hanahan
D.
(
1993
)
Precursor cells of mouse endocrine pancreas coexpress insulin, glucagon, and the neuronal proteins tyrosine hydroxylase and neuropeptide Y but not pancreatic polypeptide.
Development
118
,
1031
1039
Terazono
K.
,
Yamamoto
H.
,
Takasawa
S.
,
Shiga
K.
,
Yonemura
Y.
,
Tochino
Y.
,
Okamoto
H.
(
1988
)
A novel gene active in regenerating islets.
J. Biol. Chem
263
,
2111
2114
Thor
S.
,
Ericson
J.
,
Brännström
T.
,
Edlund
T.
(
1991
)
The homeodomain LIM protein isl-1 is expressed in subsets of neurons and endocrine cells in the adult rat.
Neuron
7
,
881
889
Turque
N.
,
Plaza
S.
,
Radvanyi
F.
,
Carriere
C.
,
Saule
S.
(
1994
)
Pax-QNR/Pax-6, a paired box-and homeobox-containing gene expressed in neurons, is also expressed in pancreatic endocrine cells.
Mol. Endocrinol
8
,
929
938
Unno
M.
,
Yonekura
H.
,
Nakagawara
K.
,
Watanabe
T.
,
Miyashita
H.
,
Moriizumi
S.
,
Okamoto
H.
(
1993
)
Structure, chromosomal location and expression of the mouse reg genes, regI and regII.
J. Biol. Chem
268
,
15974
15982
Upchurch
B. H.
,
Aponte
G. W.
,
Leiter
A. B.
(
1994
)
Expression of peptide YY in all four islet cell types in the developing mouse pancreas suggests a common peptide YY-producing progenitor.
Development
120
,
245
252
Wessells
N. K.
,
Cohen
J. H.
(
1967
)
Early pancreas organogenesis: morphogenesis, tissue interactions, and mass effects.
Dev. Biol
15
,
237
270
Wright
C. V. E.
,
Schnegelsberg
P.
,
de Robertis
E. M.
(
1988
)
XlHbox-8: a novel Xenopus homeoprotein restricted to a narrow band of endoderm.
Development
104
,
787
794
Yasuda
H.
,
Inoue
K.
,
Shibata
H.
,
Takeuchi
T.
,
Eto
Y.
,
Hasegawa
Y.
,
Sekine
N.
,
Totsuka
Y.
,
Mine
T.
,
Ogata
E.
,
Kojima
I.
(
1993
)
Existence of activin A in A and D cells of rat pancreatic islet.
Endocrinology
133
,
624
630
Yonemura
Y.
,
Takashima
T.
,
Miwa
K.
,
Miyazaki
I.
,
Yamamoto
H.
,
Okamoto
H.
(
1984
)
Amelioration of diabetes mellitus in partially depancreatized rats by polyADP-ribose synthetase inhibitors.
Diabetes
33
,
401
404
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