Autonomic involvement in the permanent metabolic programming of hyperinsulinemia in the high-carbohydrate rat model.

  title={Autonomic involvement in the permanent metabolic programming of hyperinsulinemia in the high-carbohydrate rat model.},
  author={Paul Mitrani and Malathi Srinivasan and Catherine Dodds and Mulchand S Patel},
  journal={American journal of physiology. Endocrinology and metabolism},
  volume={292 5},
Exposure to a high-carbohydrate (HC) milk formula during the suckling period results in permanent metabolic programming of hyperinsulinemia in HC rats. Previous studies have shown that hyperinsulinemia in HC rats involves a programmed hyperresponsiveness to glucose. However, the immediate onset and persistence of enhanced insulin secretion throughout life suggests a role for numerous factors that control insulin secretion. Present in vivo and in vitro studies have shown a role for altered… 

Involvement of the cholinergic pathway in glucocorticoid-induced hyperinsulinemia in rats.

Impaired Sympathoadrenal Axis Function Contributes to Enhanced Insulin Secretion in Prediabetic Obese Rats

It is suggested that low sympathoadrenal activity contributes to impaired glycaemic control in prediabetic obese rats.


The metabolic programmed mice, when submitted to vagotomy, showed improved glucose tolerance, associated with an increase of plasma insulin concentration as result of insulin clearance reduction and reduction on glucagonemia, improving glucose tolerance.

A high-carbohydrate diet in the immediate postnatal life of rats induces adaptations predisposing to adult-onset obesity.

The results suggest that hypothalamic neuropeptides respond to the increased carbohydrate availability with associated hormonal alterations during the period of dietary modulation and that these adaptations by persisting in the post-weaning period predispose the HC rats for adult-onset obesity.

Impaired muscarinic type 3 (M3) receptor/PKC and PKA pathways in islets from MSG-obese rats

The data suggest that MSG islets, whilst showing a compensatory increase in glucose-induced insulin release, demonstrate decreased islet M3/PKC and adenylate cyclase/PKA activation, possibly predisposing these prediabetic rodents to the early development of β-cell dysfunction.

Insulin Oversecretion in MSG-Obese Rats is Related to Alterations in Cholinergic Muscarinic Receptor Subtypes in Pancreatic Islets

Functional changes in and altered content of the mAChR (M1-M4) subtypes are pivotal to the demand for high pancreatic beta cell insulin secretion in MSG-obese rats, which is directly associated with vagal hyperactivity and peripheral insulin resistance.

Metabolic programming effects initiated in the suckling period predisposing for adult-onset obesity cannot be reversed by calorie restriction.

Although calorie restriction resulted in reduction in body weight gain and normalized the serum hormonal pattern, the programed predisposition for the hypersecretory capacity of islets and the hypothalamic hyperphagic response in the HC rats could not be permanently overcome by the pair-feeding imposed on HC rats.

Moderate Exercise Restores Pancreatic Beta-Cell Function and Autonomic Nervous System Activity in Obese Rats Induced by High-Fat Diet

Investigating the effects of moderate exercise training on pancreatic beta-cell function and autonomic nervous system activity in rats fed a high-fat diet found it prevented obesity, insulin resistance, and liver steatosis as well as improved total cholesterol, ALT, and AST levels.

Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

  • J. Janssen
  • Medicine, Biology
    International journal of molecular sciences
  • 2021
Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer, and drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases.

Swimming exercise at weaning improves glycemic control and inhibits the onset of monosodium L-glutamate-obesity in mice.

Results show that attenuation of MSG-hypothalamic obesity onset is caused, at least in part, by modulation of sympathoadrenal axis activity imposed by early exercise, which may be associated with subsequent glucose metabolism improvement.



Role of the autonomic nervous system in the development of hyperinsulinemia by high-carbohydrate formula feeding to neonatal rats.

Altered autonomic regulation of insulin secretion, due to the HC nutritional intervention, contributes to the development of hyperinsulinemia in 12-day-old HC rats.

Involvement of the autonomic nervous system in the in vivo memory to glucose of pancreatic beta cell in rats.

Chronic hyperglycemia brings about changes in the activity of the autonomic nervous system, which in turn are responsible, at least in part, for the generation of enhanced beta cell responsiveness to glucose in vivo.

Adaptive changes in insulin secretion by islets from neonatal rats raised on a high-carbohydrate formula.

It is shown that significant alterations at proximal and distal sites of the insulin secretory pathway in HC islets may support the hyperinsulinemic state of these rats.

Programming into adulthood of islet adaptations induced by early nutritional intervention in the rat.

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.

Altered Activity of the Autonomous Nervous System as a Determinant of the Impaired β-Cell Secretory Response after Protein-Energy Restriction in the Rat.

Whether protein-energy restriction starting after weaning could alter sympathetic and/or parasympathetic nerve activities, and whether these changes could be responsible for the lack of response to glucose of their β-cells in vivo are determined.

Altered activity of the autonomous nervous system as a determinant of the impaired beta-cell secretory response after protein-energy restriction in the rat.

It is concluded that protein-energy restriction starting early in life in rats brings about changes in the overall activity of the autonomic nervous system that, in turn, are responsible at least in part for the acquisition/maintenance of decreased beta-cell reactivity to glucose in vivo.

Muscarinic stimulation maintains in vivo insulin secretion in response to glucose after prolonged hyperglycemia.

It is concluded that prolonged hyperglycemia produces exaggerated muscarinic activation of the beta-cells that will persist > or = 3 h after the termination of the glucose infusion and normalizes in vivo insulin secretion.

Long-term effects on pancreatic function of feeding a HC formula to rats during the preweaning period.

The results show that consumption of a HC formula during the suckling period influences pancreatic islet morphology resulting in hyperinsulinemia which eventually leads to the development of obesity later in adult life.

Differential effects of prolonged hyperglycemia on in vivo and in vitro insulin secretion in rats.

Analysis of the effects of a 48-h glucose infusion in unrestrained catheterized healthy rats suggests that humoral and/or nervous interferences can counterbalance the possible perturbing effects of prolonged hyperglycemia on the normal B cell responsiveness to glucose.

Parasympathetic activity changes insulin response to glucose and neurotransmitters.

Data suggested that parasympathetic modulation is important to insulin secretion control in islets isolated from monosodium L-glutamate-obese rats.