Pancreatic Development and Maturation of the Islet B Cell

Madsen, Ole; Jensen, Jan; Blume, Niels; Petersen, Helle V.; Lund, Kaare; Karlsen, Christina; Andersen, Frank G.; Jensen, Per Bo; Larsson, Lars‐Inge; Serup, Palle

doi:10.1111/j.1432-1033.1996.435rr.x

Cited by 51 publications

(18 citation statements)

References 113 publications

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“…In agreement with previous ultrastructural studies, the present findings showed that glucagon was co-localized with all the other hormones examined, which supports, but does not prove, this hypothesis (8,13,23). Recent studies on transcriptional regulation of rat pancreatic endocrine cells suggest, however, that insulin cells do not derive from a glucagon progenitor cell (35)(36)(37)(38).…”

Section: Journal Of Endocrinology (1999) 141supporting

confidence: 81%

Co-localization of neuroendocrine hormones in the human fetal pancreas

Portela-Gomes

Johansson²,

Olding³

et al. 1999

European Journal of Endocrinology

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Objective and Design: Co-localization of the four major pancreatic hormones, and also of islet amyloid polypeptide (IAPP), peptide tyrosine tyrosine (PYY), secretin and neurotensin, has been studied in the endocrine pancreas of human fetuses at 16, 18 and 22 weeks of gestation. Methods: Double and triple immunofluorescence stainings have been used. Results: All three fetal pancreata contained cells that showed insulin, glucagon, somatostatin, pancreatic polypeptide (PP), IAPP, secretin and PYY immunoreactivity. Neurotensin cells were found in the youngest fetus and gastric inhibitory polypeptide (GIP) in the two older fetuses. Colocalization of two hormones occurred in most of the endocrine cell types in the three fetuses examined, but three hormones occurred in only a few cells and especially in the youngest fetus. Somatostatin cells were the only cell type which was largely monohormonal. Our findings showed that there are two different co-localization patterns: insulin was co-localized mainly with IAPP and glucagon, while secretin and PYY occurred together with glucagon and PP. Conclusions: These data are the first to describe secretin and neurotensin in the fetal pancreas. Two different co-localization patterns could be distinguished: insulin, IAPP and glucagon, and glucagon, secretin, PP and PYY.

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Section: Journal Of Endocrinology (1999) 141supporting

confidence: 81%

Co-localization of neuroendocrine hormones in the human fetal pancreas

Portela-Gomes

Johansson²,

Olding³

et al. 1999

European Journal of Endocrinology

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“…By 14.5 dpc in mice, the endocrine pancreas has started to develop, although islets are not yet fully formed (27,28). At this stage, the pancreata of TNDM29 mice displayed a significant reduction in all four endocrine cell types.…”

Section: Figurementioning

confidence: 99%

Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM

Ma¹,

Shield²,

Dean³

et al. 2004

J. Clin. Invest.

128

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Transient neonatal diabetes mellitus (TNDM) is a rare inherited diabetic syndrome apparent in the first weeks of life and again during early adulthood. The relative contributions of reduced islet β cell number and impaired β cell function to the observed hypoinsulinemia are unclear. The inheritance pattern of this imprinted disorder implicates overexpression of one or both genes within the TNDM locus: ZAC, which encodes a proapoptotic zinc finger protein, and HYMAI, which encodes an untranslated mRNA. To investigate the consequences for pancreatic function, we have developed a high-copy transgenic mouse line, TNDM29, carrying the human TNDM locus. TNDM29 neonates display hyperglycemia, and older adults, impaired glucose tolerance. Neonatal hyperglycemia occurs only on paternal transmission, analogous to paternal dependence of TNDM in humans. Embryonic pancreata of TNDM29 mice showed reductions in expression of endocrine differentiation factors and numbers of insulin-staining structures. By contrast, β cell mass was normal or elevated at all postnatal stages, whereas pancreatic insulin content in neonates and peak serum insulin levels after glucose infusion in adults were reduced. Expression of human ZAC and HYMAI in these transgenic mice thus recapitulates key features of TNDM and implicates impaired development of the endocrine pancreas and β cell function in disease pathogenesis.

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“…The question, therefore, arises as to what function embryonic insulin might fulfill during development. For instance, one might ask whether insulin plays an autocrine or paracrine role in pancreatic islet cell growth and differentiation, since insulin is synthesized with other hormones in developing islet cell types (1)(2)(3). Recently, this question has been addressed in a few transgenic studies.…”

mentioning

confidence: 99%

Phenotypic alterations in insulin-deficient mutant mice

Duvillié

Cordonnier

Deltour

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

254

199

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Two mouse insulin genes, Ins1 and Ins2, were disrupted and lacZ was inserted at the Ins2 locus by gene targeting. Double nullizygous insulin-deficient pups were growth-retarded. They did not show any glycosuria at birth but soon after suckling developed diabetes mellitus with ketoacidosis and liver steatosis and died within 48 h. Interestingly, insulin deficiency did not preclude pancreas organogenesis and the appearance of the various cell types of the endocrine pancreas. The presence of lacZ expressing ␤ cells and glucagon-positive ␣ cells was demonstrated by cytochemistry and immunocytochemistry. Reverse transcriptioncoupled PCR analysis showed that somatostatin and pancreatic polypeptide mRNAs were present, although at reduced levels, accounting for the presence also of ␦ and pancreatic polypeptide cells, respectively. Morphometric analysis revealed enlarged islets of Langherans in the pancreas from insulin-deficient pups, suggesting that insulin might function as a negative regulator of islet cell growth. Whether insulin controls the growth of specific islet cell types and the molecular basis for this action remain to be elucidated.Insulin is synthesized, stored, and secreted by the pancreatic islet ␤ cells in a highly regulated manner and plays a vital role in glucose homeostasis. Insulin action also results in several other pleiotropic effects that are less well documented. Embryonic insulin synthesis begins early in gestation, but fetal glycemia closely follows maternal blood glucose levels. The question, therefore, arises as to what function embryonic insulin might fulfill during development. For instance, one might ask whether insulin plays an autocrine or paracrine role in pancreatic islet cell growth and differentiation, since insulin is synthesized with other hormones in developing islet cell types (1-3). Recently, this question has been addressed in a few transgenic studies. For instance, the gene encoding PDX-1 (4, 5), a homeodomain transcription factor synthesized in adult ␤ cells and capable of transactivating insulin gene expression, has been inactivated by targeted disruption (6, 7). Agenesis of pancreas resulting from PDX-1 deficiency precluded from addressing the question of the possible role of insulin in islet cell growth and differentiation. Similarly, mice lacking the LIM homeodomain transcription factor ISL1, synthesized in all classes of islet cells in the adult, were arrested in development soon after embryonic day 9.5 (8). The requirement of ISL1 in pancreatic epithelium for the differentiation of all islet cell types was, however, demonstrated by in vitro culture of explants from ISL1-deficient embryonic day 9.5 embryos that gave rise to cells that were negative for glucagon, insulin, and somatostatin. In another study, transgenic mouse embryos expressing the gene encoding the diphteria toxin A chain under control of the rat Ins2 promoter were generated (9). The resulting genetic ablation of the insulin-producing cells did not appear to alter the development of the nontarget...

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Pancreatic Development and Maturation of the Islet B Cell

Cited by 51 publications

References 113 publications

Co-localization of neuroendocrine hormones in the human fetal pancreas

Co-localization of neuroendocrine hormones in the human fetal pancreas

Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM

Phenotypic alterations in insulin-deficient mutant mice

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