Development of β-cell mass in fetuses of rats deprived of protein and/or energy in last trimester of pregnancy

Abstract

. Development of ␤-cell mass in fetuses of rats deprived of protein and/or energy in last trimester of pregnancy. Am J Physiol Regul Integr Comp Physiol 283: R623-R630, 2002. First published May 16, 2002 10.1152 10. / ajpregu.00037.2002 malnutrition is now proposed as a risk factor of later obesity and type II diabetes. We previously analyzed the long-term impact of reduced protein and/or energy intake strictly limited to the last week of pregnancy in Wistar rats. Three protocols of gestational malnutrition were used: 1) low-protein isocaloric diet (5 instead of 15%) with pair feeding to the mothers receiving the control diet, 2) restricted diet (50% of control diet), and 3) low protein-restricted diet (50% of low-protein diet). Only isolated protein restriction induced a long-term ␤-cell mass decrease. In the present study, we used the same protocols of food restriction to analyze their short-term impact (on day 21.5 of pregnancy) on ␤-cell mass development. A 50% ␤-cell mass decrease was present in the three restricted groups, but low-protein diet, either associated or not to energy restriction, increased fetal ␤-cell insulin content. Among all the parameters analyzed to further explain our results, we found that the fetal plasma level of taurine was lowered by lowprotein diet and was the main predictor of the fetal plasma insulin level (r ϭ 0.63, P Ͻ 0.01). In conclusion, rat fetuses exposed to protein and/or energy restriction during the third part of pregnancy have a similar dramatic decrease in ␤-cell mass, and their ability to recover ␤-cell mass development retardation depends on the type of malnutrition used. Moreover, our results support the hypothesis that taurine might play an important role in fetal ␤-cell mass function. endocrine pancreas EPIDEMIOLOGICAL DATA IN VARIOUS human populations show that low birth weight and especially thinness at birth are associated with susceptibility to the development of impaired glucose tolerance/type II diabetes in adult life (16,23,26,28,31,32). This association has been interpreted as reflecting long-term effects of nutritional factors that reduce fetal growth and impair the development of tissues regulating glucose metabolism (14,29,36).Among these tissues, the endocrine pancreas, and especially ␤-cells, could suffer from fetal malnutrition. Babies with intrauterine growth retardation have a marked reduction in the size of their endocrine pancreas (41). Animal studies also report that fetal malnutrition is associated with persistently impaired pancreatic ␤-cell function and development (11,13). With the use of a low-protein diet during whole rat pregnancy, reduced proliferation rate, size, and insulin content of pancreas islets were observed in fetuses at the end of pregnancy (11,38).However, human data did not highlight a clear relationship between body weight or ponderal index (weight/height 3 ) at birth and ␤-cell function in adult age (8), and human fetal malnutrition was reported to be more strongly related to insulin resistance (5,9,10,23,26,31,40). Some...

Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet

“…The normal corticosterone levels we observed in the fetuses exposed to the low-protein diet are in agreement with previous findings [26,38] and sustain the normal level of PDX-1-and NEUROG3-positive cells observed in the LP and LPL pancreas. However, Langley-Evans and Nwagwu [39] indicated by indirect methods that glucocorticoids levels were increased in protein-restricted fetuses.…”

“…Protein as well as energy restriction dramatically decreased the beta cell mass in 21-day-old fetuses. This is consistent with the significant reduction previously described in fetuses exposed to a 50% energy restriction during the last week of gestation or exposed to a low-protein diet throughout gestation [17,22,26,27]. The impact of the low-energy diet on the beta cell mass was more noticeable when this diet was given during the entire gestation.…”

Is the Fetal Origins Hypothesis of Diabetes Supported by Animal Research? A Systematic Review and Meta-Analysis of the Evidence

“…Twenty-six studies reported on protein restriction, one using a mouse model [4], and twenty-five using a rat model . Twenty-four reported on general (caloric) undernutrition, one study using guinea pigs [30] and two on a mouse model [31,32], five using a sheep model [33][34][35][36][37] and 16 studies on rats [7,8,13,[38][39][40][41][42][43][44][45][46][47][48][49][50][51] .…”

“…Twenty-one studies were performed using rats [7][8][9][10][11][12][13][14][15][16][18][19][20][21][23][24][25][26][27][28][29], one using mice [4]. Using the random effects model we found a higher mean plasma glucose level in prenatally undernourished animals compared to the control group: a mean difference of 0.42 mmol/l (95% CI 0.07 to 0.77) ( Figure 2).…”

Adiposity in children born small for gestational age

“…Intrauterine growth retardation (IUGR) can be induced in experimental animal models by energy restriction, 16 or by feeding an isoenergetic low-protein diet [17][18] during pregnancy. Decreased foetal nutritional delivery can also be induced by ligation of uterine arteries of pregnant rats.…”