Morphological and functional adaptations of pancreatic alpha-cells during late pregnancy in the mouse

Quesada-Candela, Cristina; Tudurí, Eva; Marroquí, Laura; Alonso-Magdalena, Paloma; Quesada, Iván; Nadal, Ángel

doi:10.1016/j.metabol.2019.153963

Cited by 23 publications

(30 citation statements)

References 63 publications

(152 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4b). This is supported by the plastic capacity of the alpha-cell population described in relation to different stress situations, such as pregnancy [14], fasting periods [15], or liver resistance to glucagon i n m i c e [ 1 6 ] . T h e a n a t o m i c a l a n d f u n c t i o n a l Fig.…”

Section: Discussionmentioning

confidence: 99%

Glucagon-Producing Cell Expansion in Wistar Rats. Changes to Islet Architecture After Sleeve Gastrectomy

et al. 2021

View full text Add to dashboard Cite

Purpose Many studies about bariatric surgery have analyzed the effect of sleeve gastrectomy (SG) on glucose improvement, beta-cell mass, and islet size modification. The effects of SG on the other endocrine cells of the pancreas, such as the alpha-cell population, and their regulatory mechanisms remain less studied. Materials and Methods We focused our work on the changes in the alpha-cell population after SG in a healthy model of Wistar rats. We measured alpha-cell mass, glucose tolerance, and insulin release after oral glucose tolerance tests and plasma glucagon secretion patterns after insulin infusion. Three Wistar rat groups were employed: SG-operated, surgical control (Sham), and fasting control. Results The results obtained showed significant increases in the alpha-cell population after SG. The result was an increase in beta-cell transdifferentiation; it was shown by some expressed molecules (the loss of expression of Pdx-1 and the increase in Arx and Pax6 cells/mm2 of islet). The serum results were enhanced plasma glucagon secretion pattern after insulin infusion assays and normal glucose tolerance and insulin release after OGTT. Conclusion We concluded that SG leads to an expansion of the alpha-cell population, at expense of beta-cell; this expansion of alpha-cells is related to transdifferentiation. Plasma glucose level was not affected due to an increased glucagon response.

show abstract

Section: Discussionmentioning

confidence: 99%

Glucagon-Producing Cell Expansion in Wistar Rats. Changes to Islet Architecture After Sleeve Gastrectomy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The decline in α-cell proliferation likely follows similar progesterone-mediated inhibition that has been shown to occur in β-cells at late pregnancy. 32,51 A previous study determined that α-cell proliferation is mediated by placental lactogens and prolactin, similarly to what has been observed in β-cells. 32 However, earlier timepoints were not examined in this study 32 which could have provided crucial information as pregnancy hormones have been shown to mediate changes in pancreatic β-cells at GD9.5 to prepare the pancreas for adaptive BCM expansion at GD18.5.…”

Section: Discussionmentioning

confidence: 63%

“…This supports findings from a previous study that showed pregnant animals exhibited hypoglucagonemia and impaired glucagon secretion at GD18.5. 32 This likely occurs as a protective effect to prevent hyperglycemia in the presence of insulin resistance at late pregnancy. However, in our study, there was less suppression of serum glucagon in LP mice at GD18.5, contributing to glucose intolerance in these animals as has been shown to occur at late pregnancy in women with GDM.…”

Section: Discussionmentioning

confidence: 99%

“…Although there is evidence that a-cells contribute to hyperglycemia in patients with type 2 diabetes mellitus (T2DM) via hyperglucagonemia, [27][28][29][30][31] the dynamics of pancreatic a-cells in pregnancy have only recently been explored. 8,32 The changes in a-cell abundance during the endocrine adaptation to pregnancy were described with an expansion of a-cell mass (ACM) at GD18.5 in mice 8,32 which was impaired in glucose-intolerant pregnancies. 8 One source of new b-cells during pregnancy could derive from a molecular re-programming of glucagon-producing a-cells as part of dynamic changes in the a-cell population.…”

Section: Impact Statementmentioning

confidence: 99%

“…37 For aim 1, manual cell counting analysis determined the percentage of Insulin þ Glucagon þ (insulin and glucagon double-positive) cells as a marker for ato b-cell transitional cells. 32,[38][39][40] Alpha-cell proliferation was determined by manually counting glucagon and Ki-67 doublepositive cells. For aim 2, manual cell counting analysis determined the percentage of Insulin þ YFP þ Glucagon þ cells as a marker for a possible intermediate, transitional cell type between an a-cell and a b-cell ( Figure 1).…”

Section: Cell Counting Analysismentioning

confidence: 99%

See 2 more Smart Citations

Increased alpha and beta cell mass during mouse pregnancy is not dependent on transdifferentiation

Szlapinski

Bennett

Strutt

et al. 2020

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Maternal pancreatic beta-cell mass (BCM) increases during pregnancy to compensate for relative insulin resistance. If BCM expansion is suboptimal, gestational diabetes mellitus can develop. Alpha-cell mass (ACM) also changes during pregnancy, but there is a lack of information about α-cell plasticity in pregnancy and whether α- to β-cell transdifferentiation can occur. To investigate this, we used a mouse model of gestational glucose intolerance induced by feeding low-protein (LP) diet from conception until weaning and compared pregnant female offspring to control diet-fed animals. Control and LP pancreata were collected for immunohistochemical analysis and serum glucagon levels were measured. In order to lineage trace α- to β-cell conversion, we utilized transgenic mice expressing yellow fluorescent protein behind the proglucagon gene promoter (Gcg-Cre/YFP) and collected pancreata for histology at various gestational timepoints. Alpha-cell proliferation increased significantly at gestational day (GD) 9.5 in control pregnancies resulting in an increased ACM at GD18.5, and this was significantly reduced in LP animals. Despite these changes, serum glucagon was higher in LP mice at GD18.5. Pregnant Gcg-Cre/YFP mice showed no increase in the abundance of insulin+YFP+glucagon– cells (phenotypic β-cells). A second population of insulin+YFP+glucagon+ cells was identified which also did not alter during pregnancy. However, there was an altered anatomical distribution within islets with fewer insulin+YFP+glucagon– cells but more insulin+YFP+glucagon+ cells being present in the islet mantle at GD18.5. These findings demonstrate that dynamic changes in ACM occur during normal pregnancy and were altered in glucose-intolerant pregnancies.

show abstract

Pancreatic islet cell type–specific transcriptomic changes during pregnancy and postpartum

Chung¹,

Ma²,

Zhang³

et al. 2023

iScience

View full text Add to dashboard Cite

Morphological and functional adaptations of pancreatic alpha-cells during late pregnancy in the mouse

Cited by 23 publications

References 63 publications

Glucagon-Producing Cell Expansion in Wistar Rats. Changes to Islet Architecture After Sleeve Gastrectomy

Glucagon-Producing Cell Expansion in Wistar Rats. Changes to Islet Architecture After Sleeve Gastrectomy

Increased alpha and beta cell mass during mouse pregnancy is not dependent on transdifferentiation

Pancreatic islet cell type–specific transcriptomic changes during pregnancy and postpartum

Contact Info

Product

Resources

About