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Cited by 476Pancreatic function and diabetesGrowth Hormone and Insulin-like Growth FactorsGestational Diabetes Research and Management

Adaptation of islets of Langerhans to pregnancy: increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion

Parsons, J. A.·1992·Endocrinology
DOI 10.1210/en.130.3.1459
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Abstract

To elucidate the temporal profile of adaptive changes of the islets of Langerhans to the increased insulin demands of pregnancy, we have studied islet cell proliferation and insulin secretion during gestation in the rat. 5-Bromo-2'-deoxyuridine incorporation into dividing islet cells was significantly (P less than 0.05) increased over age-matched controls by day 10, rose continuously to a peak at day 14, and then returned to control levels by day 18. By day 20, cell division was significantly inhibited (P less than 0.05). The pattern of changes in insulin secretory profiles observed with perfused pancreata of pregnant animals was similar to that obtained for islet cell proliferation. Both the threshold of glucose-stimulated insulin secretion and the amount of above threshold insulin secretion began to diverge from controls by day 10. By day 12, the glucose-stimulation threshold was significantly decreased from 5.7 mM glucose to 3.3 mM (P less than 0.05), remained at this low level through day 15, and returned toward normal by day 20. Concomitant with the increased sensitivity of B cells to glucose, the above threshold insulin secretion was significantly increased by day 12 (P less than 0.05), peaked at day 15, and returned to control levels by day 20. This insulin secretory data demonstrates that the increased sensitivity of B cells to glucose is an important component of the adaptation of islets during pregnancy to the increased demand for insulin at physiological concentrations of plasma glucose. To correlate the above changes in islet cell proliferation and insulin secretion with levels of placental lactogen (PL), serum lactogenic hormone activity was measured by Nb2 lymphoma cell replication assays. This analysis revealed the expected biphasic pattern: a midpregnancy peak at day 12, followed by a nadir at day 14, and then continuously elevated levels until term. The bioassay data agreed with the known secretory profiles of rat (r) PL-I (midpregnancy) and rPL-II (late pregnancy). Our results provide the first systematic evaluation of changes in islet function during pregnancy in the rat. In addition, they provide evidence that rPL-I may be the critical hormonal signal which triggers the primary adaptive changes in islet function characteristic of pregnancy. The return to normal values of insulin secretion and inhibition of cell division observed at day 20 in the presence of high concentrations of rPL-II suggests that other inhibitory influences become dominant in the later stages of rat pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)

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  • Pregnant women compensate for pregnancy-induced insulin resistance through hypertrophy and hyperplasia of pancreatic β-cells and increased glucose-stimulated insulin secretion.

    “Evidence in animals suggests that, in order to maintain glucose homeostasis, pregnant women compensate for these changes through hypertrophy and hyperplasia of pancreatic β-cells, as well as increased glucose-stimulated insulin secretion (GSIS) [8].”

    From The Pathophysiology of Gestational Diabetes Mellitus (2018) · cites this paper as [8]

  • β-cell replication and hypertrophy occur during periods of intense metabolic demand in young mice and humans.

    “There is now growing evidence suggesting that β-cell replication and hypertrophy, in both young mice and humans, occurs during periods of intense metabolic demand [6,9–11], e.g. in hyperglycemia after β-cell ablation [12,13] and in the neonatal period [14–18] (Figure 1b).”

    From Expansion of β-cell mass in response to pregnancy (2010) · cites this paper as [9]

  • Lactogenic activity is vital for β-cells to increase proliferation and function in response to pregnancy.

    “Notably, this peak in DNA synthesis coincides with increased lactogen levels, suggesting that lactogenic activity is vital for the ability of β-cells to enhance proliferation and function in response to pregnancy [9].”

    From Expansion of β-cell mass in response to pregnancy (2010) · cites this paper as [9]

  • The peak in DNA synthesis coincides with increased lactogen levels.

    “Notably, this peak in DNA synthesis coincides with increased lactogen levels, suggesting that lactogenic activity is vital for the ability of β-cells to enhance proliferation and function in response to pregnancy [9].”

    From Expansion of β-cell mass in response to pregnancy (2010) · cites this paper as [9]

  • The peak of BrdU incorporation occurs about two-thirds of the way through gestation, and labeling returns to pre-pregnancy levels shortly before parturition.

    “The peak of bromodeoxyuridine (BrdU) incorporation, an indicator of DNA synthesis during S-phase, occurs about two-thirds of the way through the gestational period, with labeling returning to pre-pregnancy levels shortly before parturition.”

    From Expansion of β-cell mass in response to pregnancy (2010) · cites this paper as [9]

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Authors
Parsons, J. A.
Affiliations
University of Minnesota (US)
Venue
Endocrinology
Publisher
The Endocrine Society
Published
1992-03-01
Volume
130
Issue
3
Pages
1459-1466
ISSN
0013-7227 (ISSN-L)
DOI
10.1210/en.130.3.1459
OpenAlex
W1982391086
Cited by
476
References
0
Citations by year
2026: 4 · 2025: 10 · 2024: 15 · 2023: 21 · 2022: 28 · 2021: 26 · 2020: 24 · 2019: 16 · 2018: 17 · 2017: 21 · 2016: 16 · 2015: 26 · 2014: 26 · 2013: 21 · 2012: 17
FWCI
6.37
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Center of Excellence for Learning in Education, Science and Technology
  • National Institutes of Health (5r01dk033655-20)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-33655)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
Keywords
pancreatic islets, pregnancy, islet cell proliferation, insulin secretion, placental lactogen, beta-cell glucose sensitivity, glucose-stimulated insulin secretion
MeSH terms
Animals, Cell Division, Female, Glucose, Immunohistochemistry, Insulin, Islets of Langerhans, Placental Lactogen, Pregnancy, Pregnancy, Animal, Rats, Inbred Strains, Rats

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