Beta cell adaptation in pregnancy: a tribute to Claes Hellerström

Abstract

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.

Regulation of integrin α6A by lactogenic hormones in rat pancreatic β‐cells: Implications for the physiological adaptation to pregnancy

“…It has been shown that normalization of blood glucose by insulin treatment in pregnant rats did not change the PL levels, but prevented β‐cell proliferation . Thus, in spite of elevated levels of lactogens, PRLR and integrin α6, there is a decline in β‐cell proliferation in late pregnancy indicating that the insulin production is sufficient to maintain normoglycaemia, which is in accordance with the observation that hyperglycemia is a prerequisite for expansion of the β‐cell mass . Other factors seem also to be involved in the reversal of the β‐cell proliferation, for example, progesterone, glucocorticoids and serotonin receptor subtypes …”

“…Prolactin (PRL), placental lactogen (PL) and growth hormone (GH) are the most potent mitogens reported for primary rodent β‐cells and insulinoma cell lines in vitro . Physiologically, these hormones are particularly relevant in the adaptive β‐cell growth during pregnancy, where the β‐cell mass is markedly increased . Global depletion of PRL receptors (PRLR) in mice have been shown to impair glucose tolerance and β‐cell proliferation during pregnancy and conditional β‐cell‐specific inactivation resulted in gestational diabetes mellitus (GDM) .…”

Heterogeneity of Metabolic Defects in Type 2 Diabetes and Its Relation to Reactive Oxygen Species and Alterations in Beta-Cell Mass

“…In adulthood there are in particular two physiological conditions which lead to an increase in beta-cell mass; pregnancy and obesity (Van Assche et al, 1978; Kloppel et al, 1985; Butler et al, 2010; Hanley et al, 2010; Saisho et al, 2013). The alterations of beta-cell mass during pregnancy are elegantly reviewed by Nielsen (2016). Of importance, beta-cell mass has been found to be increased by 50% in obese individuals when compared to lean individuals (Rahier et al, 1983; Kloppel et al, 1985; Hanley et al, 2010; Saisho et al, 2013).…”

Histological and Metabolic State of Dams Suckling Small Litter or MSG-Treated Pups

“…As such, the histological analysis in our study confirms that SL Dams and MSG Dams present reduced MG development and, probably, milk synthesis. In this regard, studies have demonstrated that the metabolic activity of the MG is a major factor in plasma insulin regulation during the suckling period via a mechanism involving prolactin, the primary hormone in the milk synthesis, and with a known effect on insulin secretion and synthesis [31, 32]. Moreover, the sealing of all teats in dams or litter removal during lactation produces increased plasma insulin levels in lactating dams [33, 34].…”