Malprogramming of β-Cell Function by a Dietary Modification in the Immediate Postnatal Period
Pp. 84-106 (23)
Mulchand S. Patel and Saleh Mahmood
The development of the structure and function of the endocrine pancreas is
known to be influenced by altered nutritional experience during the fetal period.
Nutritional modifications in the suckling period are also recognized as contributing
factors to developmental programming of the endocrine pancreas. In this chapter we
describe the malprogramming of rat pancreatic islet structure and β cell functions in
response to an increased intake of carbohydrate-derived calories in a milk formula
(HC) during the suckling period. Alterations in β cell function of HC rat pups result in
the development of hyperinsulinemia due to β cell plasticity in the immediate postnatal
period. These modifications include: altered islet architecture and increased insulinproducing
mass, increased insulin secretion capacity with a leftward shift in glucosestimulated
insulin secretion, insulin secretion in the absence of glucose and/or Ca2+,
increased gene transcription of several genes crucial for β cell development and
function, and increased parasympathetic input, as well as malprogramming of
orexigenic circuitry in the hypothalamus. Interestingly, these alterations in β cell
function are maintained even after weaning of HC rats on a standard rodent chow,
resulting in adult-onset obesity due to development of hyperphagia. It is possible that
early introduction of carbohydrate-rich infant supplemental foods could contribute to
modified β cell functions in infants which could, in turn, over a longer period
predispose to the development of childhood obesity and/or adult-onset obesity and its
associated metabolic complications including type 2 diabetes.
Artificial rearing of rat pups, β cell neogenesis, β cell proliferation,
Hyperinsulinemia, Hypothalamic programming, Insulin secretion, Metabolic
programming, Nutritional modification, Obesity, Pdx-1 gene expression.
Department of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, USA.