Impact of Low Dose Prenatal Ethanol Exposure on Glucose Homeostasis in Sprague-Dawley Rats Aged up to Eight Months

Abstract

Excessive exposure to alcohol prenatally has a myriad of detrimental effects on the health and well-being of the offspring. It is unknown whether chronic low-moderate exposure of alcohol prenatally has similar and lasting effects on the adult offspring’s health. Using our recently developed Sprague-Dawley rat model of 6% chronic prenatal ethanol exposure, this study aimed to determine if this modest level of exposure adversely affects glucose homeostasis in male and female offspring aged up to eight months. Plasma glucose concentrations were measured in late fetal and postnatal life. The pancreas of 30 day old offspring was analysed for β-cell mass. Glucose handling and insulin action was measured at four months using an intraperitoneal glucose tolerance test and insulin challenge, respectively. Body composition and metabolic gene expression were measured at eight months. Despite normoglycaemia in ethanol consuming dams, ethanol-exposed fetuses were hypoglycaemic at embryonic day 20. Ethanol-exposed offspring were normoglycaemic and normoinsulinaemic under basal fasting conditions and had normal pancreatic β-cell mass at postnatal day 30. However, during a glucose tolerance test, male ethanol-exposed offspring were hyperinsulinaemic with increased first phase insulin secretion. Female ethanol-exposed offspring displayed enhanced glucose clearance during an insulin challenge. Body composition and hepatic, muscle and adipose tissue metabolic gene expression levels at eight months were not altered by prenatal ethanol exposure. Low-moderate chronic prenatal ethanol exposure has subtle, sex specific effects on glucose homeostasis in the young adult rat. As aging is associated with glucose dysregulation, further studies will clarify the long lasting effects of prenatal ethanol exposure.

Metabolic effects following periconceptional alcohol exposure in rat adult offspring: modulations by a postnatal western diet

“…Indeed, persistent hyperinsulinemia is reported to occur from the first day of postnatal life in the rat following maternal EtOH-exposure throughout pregnancy (25% in drinking water, >30E%) . This is consistent with our own data that more moderate maternal alcohol consumption (6% v/v via a liquid diet, ~15E% daily) throughout pregnancy results in hyperinsulinemia in male, but not female rat offspring at 4 months of age (Probyn et al, 2013c). Collectively, these studies highlight that maternal alcohol consumption during pregnancy can alter glucose metabolism in offspring.…”

“…Glucose (1g/kg body weight) and insulin (0.75 U/kg body weight) tolerance tests (GTT & ITT) were performed at 6 months (n = 10-11 per group) as described previously (Probyn et al, 2013c). Plasma glucose levels were determined using a Cobas Integra 400 Plus Chemistry Analyzer and insulin concentrations by rat insulin RIA kit (Cat#RI-13K, Millipore Australia, Kilsyth, VIC, AUS).…”

“…Indeed, fetuses exposed to a range of adverse intrauterine environments including malnutrition , placental insufficiency , and alcohol (Chen and Nyomba, 2003b, Probyn et al, 2013c have an increased risk of adult onset metabolic dysfunction. Low birth weight, insulin resistance, and altered regulation of hepatic glucose output are commonly demonstrated in these models (Chen and Nyomba, 2003b, Probyn et al, 2013c. Intriguingly, these effects are often programmed in a sex-specific manner, with males consistently more adversely affected than females (Probyn et al, 2013c).…”

“…Low birth weight, insulin resistance, and altered regulation of hepatic glucose output are commonly demonstrated in these models (Chen and Nyomba, 2003b, Probyn et al, 2013c. Intriguingly, these effects are often programmed in a sex-specific manner, with males consistently more adversely affected than females (Probyn et al, 2013c). The periconceptional period appears to be a particularly susceptible developmental window for programming of disease .…”

“…Animal models of undernutrition (Jaquiery et al, 2012), low protein diet (Bol et al, 2009) and uteroplacental insufficiency (Joss- Moore et al, 2010) in various species have confirmed this. Prenatal alcohol exposure has been extensively investigated in relation to alterations in glucose and insulin metabolism (Probyn et al, 2013c, Chen and Nyomba, 2003a. Considering the strong links between insulin resistance, obesity and inflammation Spiegelman, 1998, Fantuzzi, 2005), relatively less is known about the consequences of maternal alcohol consumption on adult obesity (Dobson et al, 2012), especially when consumed around conception only.…”