The pancreatic β-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes

Abstract

. The pancreatic β-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes. Molecular and Cellular Endocrinology, Elsevier, 2009, 304 (1-2) Please cite this article as: Nadal, A., Alonso-Magdalena, P., Soriano, S., Quesada, I., Ropero, A.B., The pancreatic ␤-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes, Molecular and Cellular Endocrinology (2008), doi:10.1016/j.mce.2009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. THE PANCREATIC -CELL AS A TARGET OF ESTROGENS AND XENOESTROGENS: IMPLICATIONS FOR BLOOD GLUCOSE HOMEOSTASIS AND DIABETESAngel Rosen & Spiegelman, 2006;Fritsche et al., 2008). During the fasting state, insulin remains at low levels because plasma glucose concentration is low. In this situation, the levels of the counter-regulatory hormones, glucagon, adrenaline and corticosteroids are increased to promote hepatic glucose production. In contrast, insulin, the only hormone in the body able to decrease blood glucose levels, is increased during the fed state. Insulin decreases blood glucose by promoting adipocyte and muscle glucose uptake, as well as by preventing the liver from producing glucose by suppressing glycogenolysis and gluconeogenesis (Fritsche et al., 2008). neurotransmitters, hormones and nutrients, among which glucose is the most important.Normally, in response to short glucose stimulation, insulin biosynthesis is regulated by the increased translation of the preproinsulin transcript. After a prolonged glucose exposure, however, it is regulated via the insulin gene transcription (Orland et al., 1985;Permutt & Rotwein, 1983;Poitout et al., 2006). Both transcriptional and translational regulation of insulin biosynthesis is essential to maintain the intracellular stores of insulin on a long term basis.The secretory response of -cells depends on their electrical activity. This consists of oscillations of the membrane potential that range from electrically silent periods to depolarised plateaus on which Ca 2+ -action potentials originate (Rorsman et al., 2000).The classical stimulus-secretion coupling that drives insulin release involves the closure of K ATP channels by increasing the intracellular ATP/ADP ratio (Ashcroft et al., 1984) and diadenosine polyphosphates concentration (DPs) (Ripoll et al., 1996) oscillatory pattern is originated (Nadal et al., 1999;Santos et al., 1991;Valdeolmillos et al., 1989), which triggers a pulsatile insulin secretion (Barbosa et al., 1998;Gilon et al., 1993;Dyachok et al., 2008). Estrogens, estrogen receptors and blood glucose homeostasisT...

The Impact of Polycystic Ovarian Syndrome on Gestational Diabetes

“…One might raise the question whether the maternal endocrine status before placentation and/or after IVF stimulation possibly influences glucose tolerance in women with PCOS. Furthermore, elevated estrogen levels lead to an excessive stimulation of estrogen receptor alpha in the pancreatic beta cells, producing exaggerated insulin signaling that may cause an increased state of insulin resistance in peripheral tissues (Nadal et al, 2009). Moreover, IVF is known to lead to an increased risk for maternal complications, including GDM independently of the presence of PCOS (Pinborg et al, 2004) (Shevell et al, 2005).…”

Stanowisko Polskiego Towarzystwa Endokrynologicznego dotyczące związków endokrynnie czynnych (EDC)

“…Recent studies have shown the importance of oestradiol for energy balance and glucose homeostasis [76]. Therefore, EDCs may also play a key role in this pathophysiology.…”

“…Epidemiological data have pointed to a relationship between exposure to dioxins, impaired tissue glucose transport and utilisation, as well as diabetes [78]. BPA may affect the pancreatic cells [76]. It has been demonstrated that long exposure to BPA leads to tissue insulin resistance [79].…”

“…Estradiol może odgrywać kluczową rolę w utrzymaniu homeostazy gospodarki węglowodano-wej i równowagi energetycznej [76]. Związki endokrynnie czynne mogą więc również odgrywać rolę w jej patofizjologii.…”

“…Bisfenol A może wpływać na komórki b trzustki [76]. Wykazano również, że dłu-gotrwała ekspozycja na BPA może prowadzić do insulinooporności [79].…”