Postnatal Neogenesis of Islets of Langerhans in the Mouse

Bunnag, S

doi:10.2337/diab.15.7.480

Cited by 32 publications

(12 citation statements)

References 10 publications

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“…The calculation of new cell birth rate (CBR) was based on [3H]-thymidine labeling indices and the assumption that the S-phase of all 4 islet cell types is 6 hr in length and remains as 6 hr throughout the developmental period. This number was based on the data for B-cells for adult mice as reported by Bunnag (1966) and Logothetopoulos (1972) and for fetal mice reported by Denffer (1970). More recent publication (Swenne, 1982) on cultured fetal rat islet cells further showed that fetal rat B-cell also has a DNA synthesis phase of 6 hr, adding credence to the result of analysis for B-cells in the present study.…”

Section: Discussionmentioning

confidence: 50%

“…Using differential stain and radioautography Bunnag (1966) and Denffer (1970) were the earlier workers who studied the cell proliferation of pancreatic B-cells in rodents. Denffer (1970) showed that [3H]-thymidine labeling indices were highest during the last few days of gestation in mice.…”

Section: Cell Proliferative Activitiesmentioning

confidence: 99%

“…The report of Denffer (1970) showing a maximum of 21% of [3H]-thymidine labeling indices in beta cell population of fetal and neonatal mice and that of Bunnag (1966) showing 0.5% of labeling index in adult mouse islets were the first reports to establish that normal differentiated beta cells do divide and can contribute to the final beta cell population in rodents.…”

Section: Introductionmentioning

confidence: 99%

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Growth dynamics of pancreatic islet cell populations during fetal and neonatal development of the rat

Kaung

1994

Developmental Dynamics

136

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Rats from 18 days fetal to 28 days neonatal ages were studied for the total population sizes and cell proliferation activities of insulin secreting B cells, glucagon secreting A cells, somatostatin secreting D cells, and pancreatic polypeptide secreting PP cells. Cell population sizes were assessed by morphometric quantitation of immunohistochemically stained cells by a linear scanning method and cell proliferation activities were estimated by r3HI-thymidine labeling indices of these cell populations. There was a continuous increase in population sizes for all 4 islet cell types, with the fastest increase occurring in the last 4 days of gestation. The accelerated growth of these islet cell populations during late gestation was accomplished by a high cell proliferative activity at 20-22 days of gestation and a large influx of undifferentiated epithelial cells differentiating into the specific islet cell populations during this period. There was a reduction of population growth and cell proliferation for all islet cell types during the first 3-4 days of life. Growth activities continued for all islet cell populations after the 4th postnatal day, with a renewed acceleration in growth activities for B and A cells at this time. After the 10th neonatal day, the cell proliferation and total population growth continued at slow rates for all 4 islet cell types. The contribution from undifferentiated epithelial cells into the specific islet cell populations was negligible for B and A cells but continued at a low rate for PP and D cells during the first 10 days after birth. For B and A cell populations, there was a possibility that some cell loss occurred during the first 10 days of neonatal life. These dynamic changes of the growth characteristics provide a basis for understanding the abnormal growth of the endocrine pancreas. 0 1994 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 50%

Section: Cell Proliferative Activitiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Growth dynamics of pancreatic islet cell populations during fetal and neonatal development of the rat

Kaung

1994

Developmental Dynamics

136

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“…It has been suggested that new lobes, including new islets, are constantly generated in the adult pancreas 13,32 . In contrast, the data presented here support the idea that the number of islets during adult life is fixed, with homeostatic responses (for example, b-cell expansion) being performed by differentiated cells residing in these structural units.…”

Section: Discussionmentioning

confidence: 99%

Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation

Dor

Brown

Martinez

et al. 2004

Nature

2,124

1,823

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generate and maintain the correct number of cells is a fundamental problem in biology. In principle, tissue turnover can occur by the differentiation of stem cells, as is well documented for blood, skin and intestine, or by the duplication of existing differentiated cells. Recent work on adult stem cells has highlighted their potential contribution to organ maintenance and repair. However, the extent to which stem cells actually participate in these processes in vivo is not clear. Here we introduce a method for genetic lineage tracing to determine the contribution of stem cells to a tissue of interest. We focus on pancreatic b-cells, whose postnatal origins remain controversial. Our analysis shows that pre-existing b-cells, rather than pluripotent stem cells, are the major source of new b-cells during adult life and after pancreatectomy in mice. These results suggest that terminally differentiated b-cells retain a significant proliferative capacity in vivo and cast doubt on the idea that adult stem cells have a significant role in b-cell replenishment.The literature on pancreatic b-cells and islets of Langerhans is replete with studies suggesting various mechanisms for b-cell homeostasis and regenerative repair. Early studies on patterns of [ 3 H]thymidine incorporation indicated that adult pancreatic endocrine cells belong to a class of tissues that could be maintained by the self-duplication of differentiated cells [1][2][3] . More recent immunohistochemical observations suggest a stem-cell origin for islet cells, including insulin-expressing b-cells 4 . It has been proposed that these adult pancreatic stem or progenitor cells reside in the epithelium of pancreatic ducts 5,6 , inside islets 7 or in the bone marrow 8 . Others have suggested that b-cells form in the adult by transdifferentiation of pancreatic acinar cells 9 , islet cells that express hormones other than insulin 10 , or splenocytes 11 . In addition to explaining the formation of new b-cells within existing islets, it has also been suggested that whole new islets form (islet neogenesis) by clustering of new b-cells that are derived from stem cells 5,12,13 . However, all of these models and suggestions are, for the most part, based on the interpretation of static histological data rather than direct lineage analysis 14 .We developed a simple method for distinguishing stem-cellderived b-cells from the progeny of pre-existing b-cells. Fully differentiated b-cells, defined here as post-natal cells transcribing the insulin gene, are heritably labelled in transgenic mice with a tamoxifen-inducible Cre/lox system ('pulse'). The label is the expression of the human alkaline phosphatase protein, which can be detected by a histochemical stain. After a long period, during which turnover occurs ('chase'), b-cells are examined for the presence of the label. Cells generated after the pulse are labelled if and only if they are the progeny of pre-existing (labelled) b-cells; new b-cells derived from any non-b source, including stem cells, are not labelled. Differ...

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“…This is in con¬ trast to the studies of Ziegler et al (1974) and Koncz et al (1976) in which rats successfully transplanted with adult islets of Langerhans occasionally relapsed into a diabetic state. This may reflect the decreased ability of adult islets to divide compared with foetal and neonatal tissue (Blum et al 1963) or the absence of grafted duct tissue which may be the source of new ß cells (Bunnag, 1966). Duct tissue is present in the neonatal islet transplants.…”

Section: Discussionmentioning

confidence: 98%

Neonatal Islet Cell Transplantation in the Diabetic Rat: Effect on Hepatic Enzyme Activity and Glucose Homeostasis

Y¹,

Smythe²,

Slater³

et al. 1977

Journal of Endocrinology

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Intraperitoneal transplantation of collagenase-digested, isogeneic, neonatal rat pancreatic tissue successfully reversed streptozotocin-induced diabetes in 77% of recipients. The low serum immunoreactive insulin, hyperglycaemia, glycosuria and weight loss, characteristic of the diabetic animal, were corrected and the reduced activities of hepatic glucokinase and pyruvate kinase, and the low glycogen concentration of the liver of diabetic rats were restored to normal. Forty-three per cent of the successfully transplanted rats became normoglycaemic within 1 month of transplantation whereas 57% took from 1 to 6 months to achieve normoglycaemia and displayed a mild glucose intolerance when subjected to a glucose load. The rats which had not become normoglycaemic 6 months after transplantation showed some amelioration of the diabetic state, as shown by increased serum immunoreactive insulin and hepatic glycogen concentration and a slow weight gain compared with diabetic controls.

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Postnatal Neogenesis of Islets of Langerhans in the Mouse

Cited by 32 publications

References 10 publications

Growth dynamics of pancreatic islet cell populations during fetal and neonatal development of the rat

Growth dynamics of pancreatic islet cell populations during fetal and neonatal development of the rat

Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation

Neonatal Islet Cell Transplantation in the Diabetic Rat: Effect on Hepatic Enzyme Activity and Glucose Homeostasis

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