Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy

Nalla, Amarnadh; Ringholm, Lene; Søstrup, Brigitte; Højrup, Peter; Thim, Lars; Levery, Steven B.; Vakhrushev, Sergey Y.; Billestrup, Nils; Mathiesen, Elisabeth R.; Damm, Peter; Nielsen, Jens Høiriis

doi:10.1111/aogs.12505

Cited by 8 publications

(7 citation statements)

References 42 publications

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“…We have found that serum from non-diabetic pregnant can induce Ngn3 expression in pancreas from fetal rats in vitro [ 9 ] suggesting that circulating factors are involved in promoting beta cell formation during pregnancy. We have identified a number of peptides in serum from healthy pregnant women that may be involved in the increase in beta cell mass [ 23 ]. Recently we found that certain integrins are involved in the beta cell adaptation to pregnancy in the rat [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Possible mechanisms involved in improved beta cell function in pregnant women with type 1 diabetes

Nalla

Ringholm

Sørensen

et al. 2020

Heliyon

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Pregnancy is known to be associated with an increased demand for insulin that is normally compensated by an increased beta cell mass and insulin secretion. Recent studies have suggested enhanced beta cell function during pregnancy in women with type 1 diabetes (T1D). To explore the possible mechanisms behind enhanced beta cell function during pregnancy in women with T1D we investigated the impact of circulating factors in serum from nine women from each group of pregnant women with and without T1D, after pregnancy and non-diabetic non-pregnant women on rat islet cell proliferation and apoptosis, and on T-lymphocyte activation. In addition, circulating levels of pancreatic hormones and selected cytokines and adipokines were measured. Rat islet cell proliferation was higher in serum from pregnant women with T1D (p < 0.05) compared to T1D women after pregnancy. Apoptosis in INS-1E cell was lower (p < 0.05) in serum from pregnant women with T1D compared to T1D women after pregnancy. T-lymphocyte cell (Jurkat) proliferation was reduced by serum from pregnant women without T1D only (p < 0.05). Higher C-peptide levels and lower levels of ghrelin, IL-6, MCP-1, IL-8 and adipsin were observed in pregnant women with T1D compared to T1D women after pregnancy. In conclusion, the improved beta cell function in women with T1D during pregnancy may be due to lower levels of proinflammatory cytokines and/or higher levels of pregnancy-associated growth factors.

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Section: Discussionmentioning

confidence: 99%

Possible mechanisms involved in improved beta cell function in pregnant women with type 1 diabetes

Nalla

Ringholm

Sørensen

et al. 2020

Heliyon

Self Cite

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“…When we added serum from pregnant women in third trimester to cultures of dispersed fetal rat pancreas isolated at gestational day 21.5 we found a marked increase in Ngn-3 mRNA expression, in particular in the fibroblast-like monolayer ( 30 ). We are currently searching for factors in serum from pregnant women that influence beta cell growth and function ( 33 ).…”

Section: Role Of Beta Cell Neogenesismentioning

confidence: 99%

Beta cell adaptation in pregnancy: a tribute to Claes Hellerström

Nielsen

2016

Upsala Journal of Medical Sciences

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Pregnancy is associated with a compensatory increase in beta cell mass. It is well established that somatolactogenic hormones contribute to the expansion both indirectly by their insulin antagonistic effects and directly by their mitogenic effects on the beta cells via receptors for prolactin and growth hormone expressed in rodent beta cells. However, the beta cell expansion in human pregnancy seems to occur by neogenesis of beta cells from putative progenitor cells rather than by proliferation of existing beta cells. Claes Hellerström has pioneered the research on beta cell growth for decades, but the mechanisms involved are still not clarified. In this review the information obtained in previous studies is recapitulated together with some of the current attempts to resolve the controversy in the field: identification of the putative progenitor cells, identification of the factors involved in the expansion of the beta cell mass in human pregnancy, and the relative roles of endocrine factors and nutrients.

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“…Isolated proliferative fractions contained PL, kininogen-1, fibrinogen-α-chain, α1-antitrypsin, apolipoprotein-A1, angiotensinogen, and serum albumin. Furthermore, the authors also discovered that the fractions had an inhibiting effect on insulinoma cell proliferation, suggesting that the activity of those factors could significantly contribute to the regulation of metabolic adaptations throughout pregnancy [42].…”

Section: Role In Pancreatic Beta Cellsmentioning

confidence: 99%

“…Human studies suggest that lactogens are less effective in the regulation of beta cell adaptations to pregnancy. For example, Nalla et al collected serum samples from pregnant (early and late pregnancy) and non-pregnant women [42]. Subsequently, the effect of the sample administration was examined on rat neonatal β-cells and the rat insulinoma cell line.…”

Section: Role In Pancreatic Beta Cellsmentioning

confidence: 99%

“…Moreover, it simultaneously acts as a stimulator of beta cell proliferation and has an anti-apoptotic effect on islet beta cells. However, it is important to mention that its proliferative effect on the population of human beta cells is less pronounced [40][41][42][43]45,46]. The mechanisms of the biological activity of placental lactogen (PL) in pancreatic β-cells.…”

Section: Role In Pancreatic Beta Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Placental Lactogen as a Marker of Maternal Obesity, Diabetes, and Fetal Growth Abnormalities: Current Knowledge and Clinical Perspectives

Sibiak

Jankowski

Gutaj

et al. 2020

JCM

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Placental lactogen (PL) is a peptide hormone secreted throughout pregnancy by both animal and human specialized endocrine cells. PL plays an important role in the regulation of insulin secretion in pancreatic β-cells, stimulating their proliferation and promoting the expression of anti-apoptotic proteins. Cases of pregnancy affected by metabolic conditions, including obesity and diabetes, are related to alterations in the PL secretion pattern. Whereas obesity is most often associated with lower PL serum concentrations, diabetes results in increased PL blood levels. Disruptions in PL secretion are thought to be associated with an increased prevalence of gestational complications, such as placental dysfunction, diabetic retinopathy, and abnormalities in fetal growth. PL is believed to be positively correlated with birth weight. The impaired regulation of PL secretion could contribute to an increased incidence of both growth retardation and fetal macrosomia. Moreover, the dysregulation of PL production during the intrauterine period could affect the metabolic status in adulthood. PL concentration measurement could be useful in the prediction of fetal macrosomia in women with normal oral glucose tolerance test (OGTT) results or in evaluating the risk of fetal growth restriction, but its application in standard clinical practice seems to be limited in the era of ultrasonography.

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Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy

Abstract: Pregnancy serum is able to stimulate proliferation of rat beta cells. We have identified several circulating factors that may contribute to beta cell adaptation to pregnancy. Further studies are needed to elucidate their possible role in glucose homeostasis in the mother and her offspring.

Cited by 8 publications

References 42 publications

Possible mechanisms involved in improved beta cell function in pregnant women with type 1 diabetes

Possible mechanisms involved in improved beta cell function in pregnant women with type 1 diabetes

Beta cell adaptation in pregnancy: a tribute to Claes Hellerström

Placental Lactogen as a Marker of Maternal Obesity, Diabetes, and Fetal Growth Abnormalities: Current Knowledge and Clinical Perspectives

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