Expression of PDX-1 Is Reduced in Pancreatic Islets from Pups of Rat Dams Fed a Low Protein Diet during Gestation and Lactation

Abstract

Intrauterine and early postnatal malnutrition has profound consequences on fetal and postnatal development in both humans and animals. In addition, low birth weight has been reported to be associated with impaired insulin secretion, insulin resistance and diminished area of pancreatic islets. Because the transcription factor pancreatic and duodenal homeobox 1 (PDX-1) is important for the maintenance of B-cell physiology, PDX-1 expression and islet area were assessed in neonatal rats of dams fed low (6%) or normal (17%) protein diets during pregnancy. PDX-1 protein and mRNA levels, as well as insulin secretion and islet area, were measured after 28 d of life in normal, low protein and recovered rats whose dams consumed a normal protein diet after delivery. Insulin secretion by isolated islets in response to 2.8 and 16.7 mmol glucose/L was reduced in 28-d-old low protein rats compared with the control (P < 0.05). At birth and after 28 d of life, the islet area and PDX-1 protein expression were also reduced (P < 0.05). In contrast, PDX-1 mRNA levels in islets from 28-d-old low protein rats were not different from control rats. PDX-1 protein expression in pancreatic islets, the area of islets and insulin secretion were restored in recovered rats, whereas PDX-1 mRNA levels were higher than in normal rats (P < 0.05). These results suggest a link among diminished PDX-1 protein expression, a reduction in islet area and impaired insulin secretion in low protein rats. The reintroduction of a normal diet early in life restored islet area and cell physiology.

Experimental Intrauterine Growth Restriction Induces Alterations in DNA Methylation and Gene Expression in Pancreatic Islets of Rats

“…In this report, we use the * This work was supported, in whole or in part, by National Institutes of Health Grants HG004401 and HD044078 (to J. M. G.), DK55704 and DK062965 (to R. A. S.), and AG21654 and AG18381 (to N. B. 4 The abbreviations used are: T2DM, type 2 diabetes mellitus; IUGR, intrauterine growth restriction; HELP, HpaII tiny fragment enrichment by ligation-mediated PCR; CpG/CG, cytosine-guanine dinucleotide; RT, reverse transcription. …”

“…Perturbations in the intrauterine environment resulting in poor fetal growth increase the susceptibility for age-related diseases, particularly type 2 diabetes mellitus (T2DM) 4 and cardiovascular disease (1,2). Moreover, intrauterine growth restriction (IUGR) can cause permanent and progressive changes in gene expression, affecting important metabolically active tissues such as pancreatic islets (3)(4)(5)(6).…”

“…Moreover, intrauterine growth restriction (IUGR) can cause permanent and progressive changes in gene expression, affecting important metabolically active tissues such as pancreatic islets (3)(4)(5)(6). These changes are often present at birth or during early life, and can precede the development of overt disease in rodents by months and in humans by decades.…”

Metabolic Syndrome Development in Relation to Low Birth Weight

“…Research on different animals reveals that there is a higher chance of non-insulin dependent diabetes mellitus in low birth weight offspring (Rich-Edwards et al, 1999;Lindsay et al, 2000;Miet al, 2000). Research on animals proves that nutrition restriction before birth effect birth weight and metabolism of insulin and glucose in adult or later age (Arantes et al, 2002;Holness, 1996;Hales et al, 1996). There is increased risk of onset of non-insulin dependent diabetes mellitus in humans and decreased secretion of insulin and abnormal glucose metabolism in rats and sheep ( Limesand et al, 2006;Hale and Ozanne, 2003).…”

The effects of intrauterine undernutrition on pancreas ghrelin and insulin expression in neonate rats

“…Although these adaptations may be beneficial for short-term survival, they can lead to permanent alterations in body structure and metabolism, and thereby to cardiovascular and metabolic diseases in adult life (Arantes et al 2002). There is a genetic component underlying the balance between insulin and ghrelin in regulating glucose metabolism.…”