Cell Replication in the Islets of Langerhans of Adult Rats: Effects of Pregnancy, Ovariectomy and Treatment With Steroid Hormones

Green, I. C.; Seifi, S. El; Perrin, David; Howell, S. L.

doi:10.1677/joe.0.0880219

Cited by 38 publications

(24 citation statements)

References 11 publications

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“…All in all, it appears that progesterone treatment promotes proliferation of already differentiated endocrine cells, rather than the process of differentiation of non-endocrine stem cells to endocrine cells. This situation is similar to the condition of pregnancy, where increased progesterone levels (36) are associated with increased islet-cell proliferation (10,(37)(38)(39) and not with islet neogenesis (40).…”

Section: Discussionsupporting

confidence: 54%

“…of these gonadal factor(s) might also explain the discrepancy between the stimulation of islet-cell proliferation by progesterone in vivo, as shown in the present study, and the inhibitory effects of progesterone on islet-cell proliferation in vitro (12)(13)(14), under which conditions such factors are absent.…”

Section: Discussioncontrasting

confidence: 51%

“…Therefore, at first sight, the physiological significance of the seemingly unspecific effect of progesterone on pancreatic cell proliferation remains undefined. It is suggested that, in the female, progesterone may prepare the pancreas for increased activity during reproduction by stimulating cell proliferation (10,(37)(38)(39). For the expression of this effect of progesterone, gonadal factor(s) play(s) an essential role.…”

Section: Discussionmentioning

confidence: 99%

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Progesterone stimulates pancreatic cell proliferation in vivo

Nieuwenhuizen

Schuiling²,

Liem³

et al. 1999

European Journal of Endocrinology

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Treatment of cyclic and pregnant rats with progesterone stimulates cell proliferation within the islets of Langerhans. It was investigated whether this effect of progesterone depends on sex and/or the presence of the gonads or the presence of oestradiol. For this purpose, Silastic tubes containing progesterone were inserted s.c. in intact and gonadectomized male and female rats, and in gonadectomized female rats treated with oestradiol. After 6 days of progesterone treatment, rats were infused for 24 h with 5-bromo-2 0 -deoxyuridine (BrdU) and dividing cells were identified in pancreatic sections by immunostaining for BrdU. Progesterone treatment increased islet-cell proliferation in intact male and female rats (P<0.05), but not in gonadectomized male and female rats or in gonadectomized female rats supplemented with oestradiol. Furthermore, in intact male and female rats, progesterone treatment also stimulated cell proliferation in extra-islet pancreatic tissue (P<0.05). Identification of the proliferating cells, by double-immunocytochemistry, revealed that progesterone treatment stimulated proliferation of both a and b cells within the pancreatic islets. In extra-islet pancreatic tissue, progesterone treatment stimulated proliferation in both duct (cytokeratin 20-immunoreactive) and non-duct cells. Progesterone treatment did not increase the number of single glucagon or insulincontaining cells outside the pancreatic islets, nor that of cytokeratin 20/insulin double-positive cells, suggesting that progesterone treatment did not stimulate differentiation of duct cells into endocrine cells. Progesterone treatment did not affect insulin responses to an i.v. glucose load (0.5 g/kg body weight). It is concluded that progesterone stimulates pancreatic cell proliferation indirectly; gonadal factor(s), not identical to oestradiol, is (are) probably involved.

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Section: Discussionsupporting

confidence: 54%

Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

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Progesterone stimulates pancreatic cell proliferation in vivo

Nieuwenhuizen

Schuiling²,

Liem³

et al. 1999

European Journal of Endocrinology

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“…Adult ␤-cell proliferation has been observed among pregnant and obese individuals for whom the demand for insulin is increased (40). During ␤-cell or pancreatic injuries, mitotic activity of ␤ cells is also increased (4,6,7,20,22,40). It has been suggested that after injury, ␤-cell regeneration may be the result of progenitor cell proliferation and differentiation (5).…”

mentioning

confidence: 99%

Selective Deletion of Pten in Pancreatic β Cells Leads to Increased Islet Mass and Resistance to STZ-Induced Diabetes

Stiles¹,

Kuralwalla-Martinez

Guo³

et al. 2006

Molecular and Cellular Biology

121

136

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Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a lipid phosphatase. PTEN inhibits the action of phosphatidylinositol-3-kinase and reduces the levels of phosphatidylinositol triphosphate, a crucial second messenger for cell proliferation and survival, as well as insulin signaling. In this study, we deleted Pten specifically in the insulin producing ␤ cells during murine pancreatic development. Pten deletion leads to increased cell proliferation and decreased cell death, without significant alteration of ␤-cell differentiation. Consequently, the mutant pancreas generates more and larger islets, with a significant increase in total ␤-cell mass. PTEN loss also protects animals from developing streptozotocin-induced diabetes. Our data demonstrate that PTEN loss in ␤ cells is not tumorigenic but beneficial. This suggests that modulating the PTEN-controlled signaling pathway is a potential approach for ␤-cell protection and regeneration therapies.␤ cells are produced through neogenesis from precursor cells and/or replication of mature and differentiated ␤ cells. During embryonic development, both neogenesis and replication contribute to the growth of the pancreas. The proliferation rate of ␤ cells in the adult pancreas, however, is relatively low. The adult pancreas undergoes slow turnover, with only approximately 0.5% mitotic activity, primarily by replication of differentiated cells (16). Nutrient and growth factors, such as high glucose concentrations, insulin-like growth factor 1 (IGF-1), and growth hormone, can induce ␤-cell replication (6, 39). Adult ␤-cell proliferation has been observed among pregnant and obese individuals for whom the demand for insulin is increased (40). During ␤-cell or pancreatic injuries, mitotic activity of ␤ cells is also increased (4,6,7,20,22,40). It has been suggested that after injury, ␤-cell regeneration may be the result of progenitor cell proliferation and differentiation (5). However, recent findings by Dor et al. suggest that in murine islets, proliferation of preexisting ␤ cells is the major mechanism for regeneration under both physiological and injury conditions (15). Together, these findings suggest that ␤ cells in pancreatic islets have a significant potential for replication. However, little is known about the factors regulating ␤-cell mass during neogenesis and adult pancreas turnover.Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is an indispensable regulator for cell growth and survival (48, 51). PTEN functions as a lipid phosphatase to dephosphorylate phosphatidylinositol triphosphate, the product of phosphatidylinositol-3-kinase (PI3K) (35, 56). By antagonizing PI3K function, PTEN inhibits the signals of insulin, IGF-1, and platelet-derived growth factor, the major mitogenic and survival factors of ␤ cells (13). As a consequence of PTEN loss, AKT serine/threonine kinase and its downstream effectors are hyperactivated (48,51). AKT is critical for ␤-cell survival both in vitro and in transplantation models (1,10,12,33,34,46,54). Re...

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“…Pregnancy entails increased -cell proliferation with an associated increase in -cell mass, which attains a maximum at the end of pregnancy (Hellman 1960, Hellerström 1963, Van Assche 1974, Green et al 1981, Marynissen et al 1983, Parsons et al 1992, 1994. Placental lactogen, growth hormone and prolactin have emerged as the main candidates for mediating pregnancy-specific changes in the -cells (for a review, see Sorenson & Brelje 1997).…”

Section: Discussionmentioning

confidence: 99%

Pancreatic islet blood flow during pregnancy in the rat: an increased islet mass is associated with decreased islet blood flow

Svensson

Bodin²,

Andersson³

et al. 2004

Journal of Endocrinology

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Increased blood perfusion of pancreatic islets is seen during various conditions of increased demand for insulin secretion. Pregnancy confers an increased need for insulin secretion, met by increased islet mass and volume as well as a decreased threshold for glucose-induced insulin secretion. In the present study, whole pancreatic and islet blood flow were studied with a microsphere technique in Wistar rats on days 15, 18 and 20 of pregnancy and days 2 and 7 post-partum. There were no changes in total pancreatic blood flow during pregnancy and the first post-partum week. Total blood perfusion through islet tissue expressed as flow per weight of whole pancreas was higher at day 15 of pregnancy. When islet blood flow was expressed per gram of islet tissue there was a decrease at day 18 of pregnancy. This decrease of islet blood flow was concomitant to a short-lived increase of the islet mass at the end of pregnancy. We conclude that upregulation of insulin output during late pregnancy does not specifically include increased net blood perfusion through the islets. One possible reason for this might be lack of synchronization between the proliferation of endocrine cells and angiogenesis, resulting in a relative decrease in islet vascular density in the islets.

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Cell Replication in the Islets of Langerhans of Adult Rats: Effects of Pregnancy, Ovariectomy and Treatment With Steroid Hormones

Cited by 38 publications

References 11 publications

Progesterone stimulates pancreatic cell proliferation in vivo

Progesterone stimulates pancreatic cell proliferation in vivo

Selective Deletion of Pten in Pancreatic β Cells Leads to Increased Islet Mass and Resistance to STZ-Induced Diabetes

Pancreatic islet blood flow during pregnancy in the rat: an increased islet mass is associated with decreased islet blood flow

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