Altered pancreas remodeling following glucose intolerance in pregnancy in mice

Abstract

Gestational diabetes mellitus increases the risk of dysglycemia postpartum, in part, due to pancreatic β-cell dysfunction. However, no histological evidence exists comparing endocrine pancreas after healthy and glucose-intolerant pregnancies. This study sought to address this knowledge gap, in addition to exploring the contribution of an inflammatory environment to changes in endocrine pancreas after parturition. We used a previously established mouse model of gestational glucose intolerance induced by dietary low protein insult from conception until weaning. Pancreas and adipose samples were collected at 7, 30 and 90 days postpartum for histomorphometric and cytokine analyses, respectively. Glucose tolerance tests were performed prior to euthanasia and blood was collected via cardiac puncture. Pregnant female mice born to dams fed a low protein diet previously shown to develop glucose intolerance at late gestation relative to controls continued to be glucose intolerant until 1 month postpartum. However, glucose tolerance normalized by 3 months postpartum. Glucose intolerance at 7 days postpartum was associated with lower beta- and alpha-cell fractional areas and higher adipose levels of pro-inflammatory cytokine, interleukin-6. By 3 months postpartum, a compensatory increase in the number of small islets and a higher insulin to glucagon ratio likely enabled euglycemia to be attained in the previously glucose-intolerant mice. The results show that impairments in endocrine pancreas compensation in hyperglycemic pregnancy persist after parturition and contribute to prolonged glucose intolerance. These impairments may increase the susceptibility to development of future type 2 diabetes.

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

“…GDM is described as diabetes that first appears during pregnancy, which regresses postpartum in most cases. Nonetheless, GDM is associated with adverse short- and long-term fetal and maternal health outcomes 14–18 necessitating the development of effective methods of intervention. Current treatments for GDM, such as lifestyle behavioral change or administration of insulin or metformin, aim to decrease hyperglycemia but do not treat the underlying causes including a suboptimal BCM.…”

“…GDM is described as diabetes that first appears during pregnancy, which regresses postpartum in most cases. Nonetheless, GDM is associated with adverse short-and long-term fetal and maternal health outcomes [14][15][16][17][18] necessitating the development of effective methods of intervention. Current treatments for GDM, such as…”

Acetone Ingestion Mimics a Fasting State to Improve Glucose Tolerance in a Mouse Model of Gestational Hyperglycemia

“…We chose GD18.5 based on previous findings that this was a time point where glucose intolerance and reduced BCM were present. We also investigated mice after parturition at PPD7.5 due to findings from a previous study showing that glucose intolerance persisted until 1 month post-partum in this model [ 6 ]. These animals were subsequently separated into an artemisinin-treated group, vehicle group, or non-treated group (non-treated non-pregnant and GD18.5 data retrieved from [ 12 ], non-treated PPD7.5 data retrieved from [ 6 ]).…”

“…We also investigated mice after parturition at PPD7.5 due to findings from a previous study showing that glucose intolerance persisted until 1 month post-partum in this model [ 6 ]. These animals were subsequently separated into an artemisinin-treated group, vehicle group, or non-treated group (non-treated non-pregnant and GD18.5 data retrieved from [ 12 ], non-treated PPD7.5 data retrieved from [ 6 ]). All pregnant-grouped females were time-mated with control diet-fed males.…”

“…GDM is diabetes that first appears during pregnancy and which normally regresses post-partum. Nonetheless, GDM is associated with adverse short-term outcomes to the offspring, such as macrosomia and respiratory distress syndrome, and longer-term issues such as childhood obesity and adult type 2 diabetes mellitus (T2DM) [ 2 , 3 , 4 , 5 , 6 ]. GDM is also a risk factor for subsequent T2DM in the mother.…”