Recombinant Lactococcus lactis expressing bioactive exendin-4 to promote insulin secretion and beta-cell proliferation in vitro

Background/Aims: Prevention of diabetes requires maintenance of a functional beta-cell mass, the postnatal growth of which depends on beta cell proliferation. Past studies have shown evidence of an effect of an incretin analogue, Exendin-4, in promoting beta cell proliferation, whereas the underlying molecular mechanisms are not completely understood. Methods: Here we studied the effects of Exendin-4 on beta cell proliferation in vitro and in vivo through analysing BrdU-incorporated beta cells. We also analysed the effects of Exendin-4 on beta cell mass in vivo, and on beta cell number in vitro. Then, we applied specific inhibitors of different signalling pathways and analysed their effects on Exendin-4-induced beta cell proliferation. Results: Exendin-4 increased beta cell proliferation in vitro and in vivo, resulting in significant increases in beta cell mass and beta cell number, respectively. Inhibition of PI3K/Akt signalling, but not inhibition of either ERK/MAPK pathway, or JNK pathway, significantly abolished the effects of Exendin-4 in promoting beta cell proliferation. Conclusion: Exendin-4 promotes beta cell proliferation via PI3k/Akt signaling pathway.

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Islet cells are the source of Wnts that can induce beta‐cell proliferation in vitro

Journal of Cellular Physiology ◽

10.1002/jcp.28584 ◽

2019 ◽

Vol 234 (11) ◽

pp. 19852-19865 ◽

Cited By ~ 1

Author(s):

Daniela A. Maschio ◽

Valquíria A. Matheus ◽

Carla B. Collares‐Buzato

Keyword(s):

Cell Proliferation ◽

Beta Cell ◽

Islet Cells ◽

Beta Cell Proliferation ◽

Proliferation In Vitro

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AAV8-mediated gene transfer of microRNA-132 improves beta cell function in mice fed a high-fat diet

Journal of Endocrinology ◽

10.1530/joe-18-0287 ◽

2019 ◽

Vol 240 (2) ◽

pp. 123-132 ◽

Cited By ~ 4

Author(s):

Niels L Mulder ◽

Rick Havinga ◽

Joost Kluiver ◽

Albert K Groen ◽

Janine K Kruit

Keyword(s):

Cell Proliferation ◽

Insulin Secretion ◽

Gene Transfer ◽

Beta Cell ◽

Beta Cells ◽

High Fat Diet ◽

Beta Cell Function ◽

Cell Function ◽

Beta Cell Proliferation ◽

High Fat

MicroRNAs have emerged as essential regulators of beta cell function and beta cell proliferation. One of these microRNAs, miR-132, is highly induced in several obesity models and increased expression of miR-132 in vitro modulates glucose-stimulated insulin secretion. The aim of this study was to investigate the therapeutic benefits of miR-132 overexpression on beta cell function in vivo. To overexpress miR-132 specifically in beta cells, we employed adeno-associated virus (AAV8)-mediated gene transfer using the rat insulin promoter in a double-stranded, self-complementary AAV vector to overexpress miR-132. Treatment of mice with dsAAV8-RIP-mir132 increased miR-132 expression in beta cells without impacting expression of miR-212 or miR-375. Surprisingly, overexpression of miR-132 did not impact glucose homeostasis in chow-fed animals. Overexpression of miR-132 did improve insulin secretion and hence glucose homeostasis in high-fat diet-fed mice. Furthermore, miR-132 overexpression increased beta cell proliferation in mice fed a high-fat diet. In conclusion, our data show that AAV8-mediated gene transfer of miR-132 to beta cells improves beta cell function in mice in response to a high-fat diet. This suggests that increased miR-132 expression is beneficial for beta cell function during hyperglycemia and obesity.

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Autonomic control of pancreatic beta cells: what is known on the regulation of insulin secretion and beta-cell proliferation in rodents and humans

Peptides ◽

10.1016/j.peptides.2021.170709 ◽

2021 ◽

pp. 170709

Author(s):

Valentine S. Moullé

Keyword(s):

Cell Proliferation ◽

Insulin Secretion ◽

Beta Cell ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Autonomic Control ◽

Beta Cell Proliferation

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Effect of glucose on beta cell proliferation and population size in organ culture of foetal and neonatal rat pancreases

Development ◽

10.1242/dev.75.1.303 ◽

1983 ◽

Vol 75 (1) ◽

pp. 303-312

Author(s):

Hue-Lee Cheng Kaung

Keyword(s):

Cell Proliferation ◽

Insulin Secretion ◽

Organ Culture ◽

Beta Cell ◽

Population Size ◽

Cell Population ◽

Beta Cell Proliferation ◽

Glucose Stimulation ◽

Foetal Tissue ◽

Effect Of Glucose

The effect of glucose on growth of the beta cell population was characterized in rat pancreatic organ culture. The effect was monitored by measuring [3H]thymidine labelling indices of beta cells during the culture period and by quantitation of beta cell population size at the end of the culture period. Foetal and neonatal pancreases and different glucose levels were compared. Glucose was found to be effective in stimulating the beta cell proliferation and beta cell population increase at 300 mg/100 ml in 18-day foetal pancreatic explants, but not in 3-day neonatal explants, when compared to the control level of 1OOmg/1OOml. A higher level of glucose (500 mg/100 ml) was ineffective and may even inhibit beta cell population growth. The higher than control levels of glucose (300 mg/100 ml and 500 mg/100 ml) were able to stimulate insulin secretion in neonatal tissue, but not in foetal tissue, although foetal tissue may develop such response later in culture. These results suggest that glucose stimulates beta cell proliferation and insulin secretion through different mechanisms. They further show that the potentiality for beta cell proliferation under glucose stimulation decreases with age of the explants and that the capacity for beta cell to proliferate as a function of glucose stimulation is limited.

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