The Role of Non-Placental Signals in the Adaptation of Islets to Pregnancy

Drynda, Robert; Peters, Catherine; Jones, Peter M.; Bowe, James

doi:10.1055/s-0034-1395691

Cited by 18 publications

(23 citation statements)

References 32 publications

(57 reference statements)

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“…On gd12, a time of rapid β-cell expansion [6], 79 out of 126 known islet GPCR ligand mRNAs were expressed at detectable levels in mouse placental extracts, as shown in Fig. 3 and (see online suppl.…”

Section: Resultsmentioning

confidence: 99%

“…Table 5. Analysis of the expression of the same mRNA species in placental extracts at gd18, when β-cell expansion has ceased [6], indicated expression of 62 GPCR ligand mRNAs (Fig. 4, see online suppl.…”

Section: Resultsmentioning

confidence: 99%

“…Tissue samples were prepared at two stages of pregnancy: gestational day (gd) 12 in mid-pregnancy when β-cell mass expansion is maximal; and gd18 in late pregnancy when the β-cell mass is no longer expanding [6]. Placenta were removed and extracted immediately while islets were isolated from whole pancreas by collagenase digestion, as described previously [15].…”

Section: Methodsmentioning

confidence: 99%

“…Failure of the β-cells to adapt appropriately leads to glucose intolerance and the eventual development of overt gestational diabetes mellitus (GDM) [2-4]. In rodents, the β-cell expansion during gestation occurs over a relatively short and well-defined period [5, 6], offering a useful experimental model in which to study the regulation of functional β-cell mass. Islet β-cell adaptive responses occur after placentation and are rapidly reversed post-partum, consistent with placental signals playing a major role in informing β-cells of the gestational stage via circulating mediators.…”

Section: Introductionmentioning

confidence: 99%

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The Placental Secretome: Identifying Potential Cross-Talk Between Placenta and Islet β-Cells

Drynda¹,

Persaud²,

Bowe³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Insulin-secreting islet β-cells adapt to the insulin resistance associated with pregnancy by increasing functional β-cell mass, but the placental signals involved in this process are not well defined. In the current study, we analysed expression of G-protein coupled receptor (GPCR) mRNAs in mouse islets and islet GPCR ligand mRNAs in placenta during pregnancy to generate an atlas of potential interactions between the placenta and β-cells to inform future functional studies of islet adaptive responses to pregnancy. Methods: Quantative RT-PCR arrays were used to measure mRNA expression levels of: (i) 342 GPCRs in islets from non-pregnant mice, and in islets isolated from mice on gestational days 12 and 18; (ii) 126 islet GPCR ligands in mouse placenta at gestational days 12 and 18. Results: At gestational day 12, a time of rapid expansion of the β-cell mass, 189 islet GPCR mRNAs were quantifiable, while 79 of the 126 known islet GPCR ligand mRNAs were detectable in placental extracts. Approximately half of the quantifiable placental GPCR ligand genes were of unknown function in β-cells. The expression of some islet GPCR and placental ligand mRNAs varied during pregnancy, with altered expression of both GPCR and ligand mRNAs by gestational day 18. Conclusion: The current study has revealed numerous potential routes for interaction between the placenta and islets, and offers an atlas to inform further functional studies of their roles in adaptive responses to pregnancy, and in the regulation of the β-cell mass.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Placental Secretome: Identifying Potential Cross-Talk Between Placenta and Islet β-Cells

Drynda¹,

Persaud²,

Bowe³

et al. 2018

Cell Physiol Biochem

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“…The hormone prolactin is known to increase pancreatic β-cell mass and function during human pregnancy, but effects on β cells during the peripartum and postpartum periods have not been delineated. In mice, a higher rate of maternal β-cell proliferation was reported in lactating groups than in nonlactating groups (36). In postpartum women with recent GDM, lactation enhances β-cell compensation for insulin resistance, resulting in better insulin sensitivity, glucose effectiveness, and first-phase insulin response to glucose according to the Bergman Minimal Model (9).…”

Section: Discussionmentioning

confidence: 99%

Lactation and Progression to Type 2 Diabetes Mellitus After Gestational Diabetes Mellitus

et al. 2015

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Background Lactation improves glucose metabolism, but its role in preventing type 2 diabetes mellitus (DM) after gestational diabetes mellitus (GDM) remains uncertain. Objective To evaluate lactation and the 2-year incidence of DM after GDM pregnancy. Design Prospective, observational cohort of women with recent GDM. (ClinicalTrials.gov: NCT01967030) Setting Integrated health care system. Participants 1035 women diagnosed with GDM who delivered singletons at 35 weeks' gestation or later and enrolled in the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy from 2008 to 2011. Measurements Three in-person research examinations from 6 to 9 weeks after delivery (baseline) and annual follow-up for 2 years that included 2-hour, 75-g oral glucose tolerance testing; anthropometry; and interviews. Multivariable Weibull regression models evaluated independent associations of lactation measures with incident DM adjusted for potential confounders. Results Of 1010 women without diabetes at baseline, 959 (95%) were evaluated up to 2 years later; 113 (11.8%) developed incident DM. There were graded inverse associations for lactation intensity at baseline with incident DM and adjusted hazard ratios of 0.64, 0.54, and 0.46 for mostly formula or mixed/inconsistent, mostly lactation, and exclusive lactation versus exclusive formula feeding, respectively (P trend = 0.016). Time-dependent lactation duration showed graded inverse associations with incident DM and adjusted hazard ratios of 0.55, 0.50, and 0.43 for greater than 2 to 5 months, greater than 5 to 10 months, and greater than 10 months, respectively, versus 0 to 2 months (P trend = 0.007). Weight change slightly attenuated hazard ratios. Limitation Randomized design is not feasible or desirable for clinical studies of lactation. Conclusion Higher lactation intensity and longer duration were independently associated with lower 2-year incidences of DM after GDM pregnancy. Lactation may prevent DM after GDM delivery.

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Lactation Duration and Progression to Diabetes in Women Across the Childbearing Years

et al. 2018

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IMPORTANCE Lactation duration has shown weak protective associations with incident diabetes (3%-15% lower incidence per year of lactation) in older women based solely on self-report of diabetes, studies initiated beyond the reproductive period are vulnerable to unmeasured confounding or reverse causation from antecedent biochemical risk status, perinatal outcomes, and behaviors across the childbearing years.OBJECTIVE To evaluate the association between lactation and progression to diabetes using biochemical testing both before and after pregnancy and accounting for prepregnancy cardiometabolic measures, gestational diabetes (GD), and lifestyle behaviors.DESIGN, SETTING, AND PARTICIPANTS For this US multicenter, community-based 30-year prospective cohort study, there were 1238 women from the Coronary Artery Risk Development in Young Adults (CARDIA) study of young black and white women ages 18 to 30 years without diabetes at baseline (1985)(1986) who had 1 or more live births after baseline, reported lactation duration, and were screened for diabetes up to 7 times during 30 years after baseline .EXPOSURES Time-dependent lactation duration categories (none, >0 to 6 months, >6 to <12 months, and Ն12 months) across all births since baseline through 30 years.MAIN OUTCOMES AND MEASURES Diabetes incidence rates per 1000 person-years and adjusted relative hazards (RH) with corresponding 95% CIs, as well as proportional hazards regression models adjusted for biochemical, sociodemographic, and reproductive risk factors, as well as family history of diabetes, lifestyle, and weight change during follow-up. RESULTSOverall 1238 women were included in this analysis (mean [SD] age, 24.2 [3.7] years; 615 black women). There were 182 incident diabetes cases during 27 598 person-years for an overall incidence rate of 6.6 cases per 1000 person-years (95% CI, 5.6-7.6); and rates for women with GD and without GD were 18.0 (95% CI, 13.3-22.8) and 5.1 (95% CI, 4.2-6.0), respectively (P for difference < .001). Lactation duration showed a strong, graded inverse association with diabetes incidence: adjusted RH for more than 0 to 6 months, 0.75 (95% CI, 0.51-1.09); more than 6 months to less than 12 months, 0.52 (95% CI, 0.31-0.87), and 12 months or more 0.53 (0.29-0.98) vs none (0 days) (P for trend = .01). There was no evidence of effect modification by race, GD, or parity. CONCLUSIONS AND RELEVANCEThis study provides longitudinal biochemical evidence that lactation duration is independently associated with lower incidence of diabetes. Further investigation is required to elucidate mechanisms that may explain this relationship.

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The Role of Non-Placental Signals in the Adaptation of Islets to Pregnancy

Cited by 18 publications

References 32 publications

The Placental Secretome: Identifying Potential Cross-Talk Between Placenta and Islet β-Cells

The Placental Secretome: Identifying Potential Cross-Talk Between Placenta and Islet β-Cells

Lactation and Progression to Type 2 Diabetes Mellitus After Gestational Diabetes Mellitus

Lactation Duration and Progression to Diabetes in Women Across the Childbearing Years

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