Placental endocrine malfunction alters maternal β-cell adaptation during pregnancy in mice

Pyruvate carboxylase (PC) activity is enhanced in the islets of obese rats, but it is reduced in the islets of type 2 diabetic rats, suggesting the importance of PC in β-cell adaptation to insulin resistance as well as the possibility that PC reduction might lead to hyperglycemia. However, the causality is currently unknown. We used obese Agouti mice (AyL) as a model to show enhanced β-cell adaptation, and type 2 diabetic db/db mice as a model to show severe β-cell failure. After comparison of the two models, a less severe type 2 diabetic Agouti-K (AyK) mouse model was used to show the changes in islet PC activity during the development of type 2 diabetes mellitus (T2DM). AyK mice were separated into two groups: mildly (AyK-M, blood glucose <250 mg/dl) and severely (AyK-S, blood glucose >250 mg/dl) hyperglycemic. Islet PC activity, but not protein level, was increased 1.7-fold in AyK-M mice; in AyK-S mice, islet PC activity and protein level were reduced. All other changes including insulin secretion and islet morphology in AyK-M mice were similar to those observed in AyL mice, but they were worse in AyK-S mice where these parameters closely matched those in db/db mice. In 2-day treated islets, PC activity was inhibited by high glucose but not by palmitate. Our findings suggest that islet PC might play a role in the development of T2DM where reduction of PC activity might be a consequence of mild hyperglycemia and a cause for severe hyperglycemia.

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β−cell adaptation/dysfunction in an animal model of dyslipidemia and insulin resistance induced by the chronic administration of a sucrose-rich diet

Islets ◽

10.4161/isl.2.6.13869 ◽

2010 ◽

Vol 2 (6) ◽

pp. 367-373 ◽

Cited By ~ 6

Author(s):

Maria del Rosario Ferreira ◽

Yolanda B. Lombardo ◽

Adriana Chicco

Keyword(s):

Insulin Resistance ◽

Animal Model ◽

Chronic Administration ◽

Β Cell ◽

Cell Adaptation

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Adipose tissue macrophages orchestrate β cell adaptation in obesity through secreting miRNA-containing extracellular vesicles

10.1101/2020.06.12.148809 ◽

2020 ◽

Author(s):

Hong Gao ◽

Zhenlong Luo ◽

Zhongmou Jin ◽

Yudong Ji ◽

Wei Ying

Keyword(s):

Adipose Tissue ◽

Insulin Secretion ◽

Extracellular Vesicles ◽

Critical Role ◽

Β Cells ◽

Β Cell ◽

Cell Adaptation ◽

Cell Functions ◽

Cell Responses ◽

Adipose Tissue Macrophages

AbstractObesity induces an adaptive expansion of β cell mass and insulin secretion abnormality. Here, we explore a novel role of adipose tissue macrophages (ATMs) in mediating obesity-induced β cell function and proliferation through releasing miRNA-containing extracellular vesicles (EVs). ATM EVs derived from obese mice notably suppress insulin secretion in both in vivo and in vitro experiments, whereas there are more proliferating β cells in the islets treated with obese ATM EVs. Depletion of miRNAs blunts the ability of obese ATM EVs to regulate β cell responses. miR-155, a highly enriched miRNA within obese ATM EVs, exerts profound regulation on β cell functions, as evidenced by impaired insulin secretion and increased β cell proliferation after miR-155 overexpression in β cells. By contrast, knockout of miR-155 can attenuate the regulation of obese ATM EVs on β cell responses. We further demonstrate that the miR-155-Mafb axis plays a critical role in controlling β cell responses. Taken together, these studies show a novel mechanism by which ATM-derived EVs act as endocrine cargoes delivering miRNAs and subsequently mediating β cell adaptation and functional dysfunction in obesity.

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Oxytocin signal contributes to the adaptative growth of islets during gestation

Endocrine Connections ◽

10.1530/ec-21-0043 ◽

2021 ◽

Author(s):

Ping Gu ◽

Yuege Lin ◽

Qi Wan ◽

Dongming Su ◽

Qun Shu

Keyword(s):

Insulin Secretion ◽

Pregnant Women ◽

Cell Function ◽

Pancreatic Β Cell ◽

Β Cells ◽

Β Cell ◽

Pancreatic Β Cells ◽

Cell Adaptation ◽

Β Cell Function ◽

Insulinoma Cells

Background: Increased insulin production and secretion by pancreatic β-cells are important for ensuring the high insulin demand during gestation. However, the underlying mechanism of β-cell adaptation during gestation or in gestational diabetes mellitus (GDM) remains unclear. Oxytocin is an important physiological hormone in gestation and delivery, and it also contributes to the maintenance of β-cell function. The aim of this study was to investigate the role of oxytocin in β-cell adaptation during pregnancy. Methods: The relationship between the blood oxytocin level and pancreatic β-cell function in patients with GDM and healthy pregnant women was investigated. Gestating and non-gestating mice were used to evaluate the in vivo effect of oxytocin signal on β-cells during pregnancy. In vitro experiments were performed on INS-1 insulinoma cells. Results: The blood oxytocin levels were lower in patients with GDM than in healthy pregnant women and were associated with impaired pancreatic β-cell function. Acute administration of oxytocin increased insulin secretion in both gestating and non-gestating mice. A three-week oxytocin treatment promoted the proliferation of pancreatic β-cells and increased the β-cell mass in gestating but not non-gestating mice. Antagonism of oxytocin receptors by atosiban impaired insulin secretion and induced GDM in gestating but not non-gestating mice. Oxytocin enhanced glucose-stimulated insulin secretion, activated the mitogen-activated protein kinase pathway, and promoted cell proliferation in INS-1 cells. Conclusions: These findings provide strong evidence that oxytocin is needed for β-cell adaptation during pregnancy to maintain β-cell function, and lack of oxytocin could be associated with the risk of GDM.

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