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Programming into adulthood of islet adaptations induced by early nutritional intervention in the rat
R Aalinkeel1, M Srinivasan, F Song
1Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA.
Insights
High carbohydrate intake in neonatal rats programs pancreatic islet function, leading to sustained hyperinsulinemia and obesity in adulthood. This early nutrition impacts long-term metabolic health.
Area of Science:
- Endocrinology
- Developmental Biology
- Nutritional Science
Background:
- Early life nutrition significantly influences long-term metabolic health.
- Pancreatic islet function is crucial for glucose homeostasis and insulin secretion.
Purpose of the Study:
- To investigate the long-term effects of high carbohydrate (HC) intake during the suckling period on pancreatic islet function in adult rats.
- To understand the molecular mechanisms underlying altered insulin secretion due to early HC exposure.
Main Methods:
- Neonatal rats were artificially reared on a high carbohydrate (HC) milk formula.
- Pancreatic islet function, including glucose-stimulated insulin secretion, was assessed in adult rats.
- Gene expression analysis (mRNA levels) of key pancreatic genes was performed.
Main Results:
- Adult rats exposed to HC formula exhibited sustained hyperinsulinemia.
- HC islets showed an altered glucose-stimulated insulin secretion pattern and insulin release without glucose.
- Increased mRNA levels of preproinsulin, transcription factors, and GLUT-2 were observed in HC islets.
Conclusions:
- Early life high carbohydrate consumption programs pancreatic islet function, leading to hyperinsulinemia.
- These adaptations in pancreatic islets contribute to the development of obesity in adult life.
- Nutritional programming during the suckling period has lasting metabolic consequences.
Abstract:
To investigate the influence of a high carbohydrate (HC) intake during the suckling period on pancreatic function in adult life, neonatal rats were artificially reared on a HC milk formula during the preweaning period and then weaned onto lab chow. In the adult HC rat, hyperinsulinemia is sustained by a variety of biochemical and molecular adaptations induced in the HC islets during the suckling period. The adult HC islets showed a distinct left shift in the glucose-stimulated insulin-secretory pattern. HC islets were also able to secrete moderate levels of insulin in the absence of glucose and in the presence of Ca(2+) channel inhibitors. In addition, the mRNA levels of preproinsulin, somatostatin transcription factor-1, upstream stimulatory factor-1, stress-activated protein kinase-2, phosphatidylinositol kinase, and GLUT-2 genes were significantly increased in HC islets. These results show that consumption of a HC formula during the suckling period programs pancreatic islet function in adult rats, resulting in the maintenance of hyperinsulinemia in the postweaning period and eventually leading to the development of obesity in adult life.