Selective effect of INGAP-PP upon mouse embryonic stem cell differentiation toward islet cells

Francini, Flavio; Zotto, Hector Herminio del; Massa, María Laura; Gagliardino, Juan José

doi:10.1016/j.regpep.2008.12.006

Cited by 6 publications

(8 citation statements)

References 37 publications

(45 reference statements)

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“…12 In the field of tissue engineering, ES-D3 cells have been used to generate 3D tissue-like structures in vitro, such as beating cardiomyocytes in a scaffold of collagen I and matrigel, 13 and to generate endodermal cells on fibronectin-coated collagen I gels.…”

Section: Introductionmentioning

confidence: 99%

Fibronectin-mediated upregulation of α5β1 integrin and cell adhesion during differentiation of mouse embryonic stem cells

Pimton

Sarkar

Sheth

et al. 2011

Cell Adhesion & Migration

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Section: Introductionmentioning

confidence: 99%

Fibronectin-mediated upregulation of α5β1 integrin and cell adhesion during differentiation of mouse embryonic stem cells

Pimton

Sarkar

Sheth

et al. 2011

Cell Adhesion & Migration

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“…This allows for β‐cells to maintain plasticity by increasing or decreasing in number, as required, to maintain glucose homeostasis throughout adulthood. The hypothesis that Reg plays a role that is independent of BCR is also suggested by the work of two research teams that programmed exocrine tissue using MafA and PDX‐1 into β‐cells, with the β‐cells not housed within multicellular islets 53,54 . Zhou et al 53 .…”

Section: Transcription Factor Expression In Bcrmentioning

confidence: 94%

“…The hypothesis that Reg plays a role that is independent of BCR is also suggested by the work of two research teams that programmed exocrine tissue using MafA and PDX‐1 into β‐cells, with the β‐cells not housed within multicellular islets 53,54 . Zhou et al 53 . used MafA, PDX‐1, and NGN3, whereas Kaneto et al 54 .…”

Section: Transcription Factor Expression In Bcrmentioning

confidence: 98%

“…The hypothesis that Reg plays a role that is independent of BCR is also suggested by the work of two research teams that programmed exocrine tissue using MafA and PDX-1 into b-cells, with the b-cells not housed within multicellular islets. 53,54 Zhou et al 53 used MafA, PDX-1, and NGN3, whereas Kaneto et al 54 combined MafA, PDX-1, and NeuroD to form new b-cells. MafA, PDX-1 and NeuroD were found to directly bind to the insulin gene promoter 54 (Fig.…”

Section: Identification Of Potential Triggers For Islet Neogenesis Anmentioning

confidence: 99%

“…Tissue neoplasia and hypoglycemia have not been seen in preclinical trials using Reg-derived islet neogenesis agents. 28,29,41,43,47,[50][51][52][53][54][65][66][67] The Reg proteins are delivered as short-lived triggers in the islet neogenesis pathway, which has many protective and redundant rate-limiting feedback loops to prevent hypoglycemia.…”

Section: Metabolic Milieumentioning

confidence: 99%

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Distinctions between islet neogenesis and β‐cell replication: Implications for reversal of Type 1 and 2 diabetes

Levetan

2010

Journal of Diabetes

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The terms “islet” and “β‐cell” are often used interchangeably, yet islets are highly complex multicellular organelles that contain the insulin‐producing β‐cells and four other cells types, all of which play a role in maintaining glucose homeostasis within a very narrow range. Although the formation of new islets in adults is rare, occurring primarily in response to pancreatic injury and major stress to the pancreas, β‐cell replication from existing cells occurs throughout adulthood. An understanding of the regulatory factors controlling pancreatic development has more clearly defined the differences between new islet formation from progenitor cells located throughout the adult pancreas and β‐cell replication occurring within existing islets. The present review sets forth to more clearly distinguish the differences between the postnatal pathways of islet neogenesis and β‐cell replication with a discussion of the potential implications for reversal of Type 1 and 2 diabetic patients using islet neogenesis agents that are now in development. For Type 1 diabetic patients, an immune tolerance agent in conjunction with an islet neogenesis agent may allow achievement of adequate islet mass, perhaps with subsequent potential to withdraw medications. For Type 2 diabetic patients, lifestyle changes and/or medications may sustain the production of new islets and limit the accelerated β‐cell apoptosis characteristic of the condition.

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Enhanced islet expansion by β‐cell proliferation in young diabetes‐prone rats fed a protective diet

Wang

Kauri

Patrick

et al. 2010

Journal Cellular Physiology

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Type 1 diabetes is inhibited in diabetes-prone BioBreeding (BBdp) rats fed a low-antigen hydrolyzed casein (HC) diet. In cereal-fed BBdp rats, islet expansion is defective accompanied by a futile upregulation of islet neogenesis without increased islet mass, due to a subtle blockage in islet cell cycle. We hypothesized that islet growth is enhanced before insulitis in HC-fed young BBdp rats and that islet neogenesis could be stimulated by a trophic factor, islet neogenesis-associated protein (INGAP). beta-Cell homeostasis was analyzed using immunohistochemistry, morphometry, laser capture microdissection and RT-PCR in BBdp rats fed HC or cereal diets. beta-cell proliferation in small and medium islets, and the number and area fraction of medium and large islets were increased in HC-fed animals. In situ islet cell cycle analysis revealed an increased proportion of proliferating S + G2 cells in medium and large islets of 25-45 day HC-fed rats. Expression of the cell cycle inhibitor, p16(INK4a) correlated with islet size and the percentage of p16(INK4a+) beta-cells increased in HC-fed BBdp rats, likely reflecting an increase in large islet area fraction. In HC-fed rats, extra-islet insulin(+) clusters (EIC), insulin(+) duct cells, large islet area fraction, and beta-cell mass were increased. Neurogenin-3 and Pdx-1, markers of beta-cell progenitors, were increased in EIC of weanling HC-fed rats. Daily injection of INGAP (30-45 days) increased the number of small islets, total islets, and insulin(+) cells in small ducts. Thus, in BBdp rats fed a protective HC diet, beta-cell expansion is enhanced through increased beta-cell proliferation and stimulation of islet neogenesis.

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Selective effect of INGAP-PP upon mouse embryonic stem cell differentiation toward islet cells

Cited by 6 publications

References 37 publications

Fibronectin-mediated upregulation of α5β1 integrin and cell adhesion during differentiation of mouse embryonic stem cells

Fibronectin-mediated upregulation of α5β1 integrin and cell adhesion during differentiation of mouse embryonic stem cells

Distinctions between islet neogenesis and β‐cell replication: Implications for reversal of Type 1 and 2 diabetes

Enhanced islet expansion by β‐cell proliferation in young diabetes‐prone rats fed a protective diet

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