Communication Dans Un Congrès Année : 2025

The offspring's β-cell maturation process during the suckling period and their insulin sensitivity in adulthood are differently impacted depending from hyperglycemic or euglycemic dams

Résumé

Gestational Diabetes Mellitus (GDM) is associated with a higher risk of type 2 diabetes (T2D) in offspring later in life, likely involving disruptions in pancreatic islets development and function in the newborn. During the breast-feeding period, β-cells undergo a maturation process that enhances their insulin secretory capacity. Furthermore, epidemiologic evidence highlights (1) the benefits of extended breastfeeding in reducing the risk of T2D in children born to mothers with GDM and (2) adaptations in the composition of GDM breast milk. However, the impact of breast milk composition during the critical βcell maturation period in the context of GDM remains unknown, even though breastfeeding represents a potential intervention target to mitigate t the effects of maternal hyperglycaemia. We developed a rodent model of maternal hyperglycaemia induced by a High Fat High Sucrose (HFHS) diet during gestation alone (4HFHS), or during gestation and lactation (7HFHS), compared to a Chow diet (euglycaemic CTL rats). Milk composition was characterised at postnatal day 1 (PND1) and at PND14 through analyses of fatty acids, amino acids, sphingolipids and lipidome profiles. The independent effects of the gestation and lactation periods were investigated by cross-fostering pups at PND0 among CTL, 4HFHS and 7HFHS dams. Pancreatic islets were isolated from offspring at PND0, PND14 and PND 220. Offspring insulin-sensitivity was studied in adulthood through oral glucose tolerance tests (OGTT) at PND60 and PND210, as well as euglycemic-hyperinsulinemic clamps at PND200, in response to hypercaloric challenge administered from PND120 to PND220. Colostrum from 4HFHS; 7HFHS and CTL dams showed 3 distinct metabotypes. These differences in composition were maintained at PND14 in 7HFHS vs CTL milk. At PND0, pups born to hyperglycaemic mothers showed islet hypertrophy and hyperplasia associated with a reduced percentage of beta cells. At PND14, the expression of genes involved in islet maturation (NeuroD, Glut2, Ins2) was increased, as well as plasma insulinemia and HOMA-β in pups adopted and suckled by 7HFHS versus 4HFHS dams. Moreover, at D220, offspring born to HFHS dams and suckled by CTL dams showed hyperglycemia (in males) and an insulin-sensitivity lower trend (in females) to in response to hypercaloric challenge. These preliminary results confirm that hyperglycaemia during gestation-lactation is associated with an adaptation of milk composition, and would have repercussions on offspring's β-cell maturation and metabolic trajectory later in their adult life according to their maternal glycemic status during gestation and lactation.

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Dates et versions

hal-05313843 , version 1 (14-10-2025)

Identifiants

  • HAL Id : hal-05313843 , version 1

Citer

Paul Bobin, Isabelle Grit, Corentin Massias, Pierre de Coppet, Agnès David-Sochard, et al.. The offspring's β-cell maturation process during the suckling period and their insulin sensitivity in adulthood are differently impacted depending from hyperglycemic or euglycemic dams. International Congress of Nutrition IUNS-ICN, International Society of Nutrition, Aug 2025, Paris, France. ⟨hal-05313843⟩
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