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Updated: Mar 10, 2026

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
Published on: January 4, 2018
Cephalic phase, reflex insulin secretion neuroanatomical and physiological characterization
H R Berthoud1,2, D A Bereiter1,2, E R Trimble1,2
1Laboratoires de Recherches Métaboliques, Institut de Biochimie Clinique, Switzerland.
The sweet taste of saccharin triggers a cephalic phase insulin response (CPIR) in rats, mediated by the autonomic nervous system. This reflex is crucial for normal glucose tolerance and may influence food behavior and obesity.
Area of Science:
- Neuroendocrinology
- Physiology
- Metabolic research
Background:
- The cephalic phase insulin response (CPIR) is an anticipatory release of insulin triggered by sensory stimuli associated with food.
- The neural pathways and physiological significance of CPIR, particularly in response to sweet tastes, require further elucidation.
Purpose of the Study:
- To investigate the neural mediation of the sweet taste-induced CPIR in rats.
- To explore the central neural pathways involved in this reflex.
- To assess the physiological relevance of CPIR in glucose tolerance and its potential role in dietary obesity.
Main Methods:
- Utilized chronically catheterized, freely moving male Wistar rats.
- Employed streptozotocin-induced diabetes model with intrahepatic islet transplantation for denervated beta-cell preparations.
- Conducted electrophysiological recordings and semi-micro central nervous system manipulations.
- Assessed oral glucose tolerance and behavioral responses to palatable foods.
Main Results:
- Saccharin reliably triggered CPIR without altering glycemia, indicating neural mediation via the autonomic nervous system.
- Denervated beta-cell preparations showed a complete lack of CPIR, confirming the absence of gastrointestinal hormonal involvement.
- CPIR demonstrated resistance to extinction, suggesting an unconditioned reflex component.
- Preliminary findings suggest CPIR organization at the brain stem/midbrain level with diencephalic modulation.
- Lack of CPIR led to pathological oral glucose tolerance; exaggerated CPIR was linked to behavioral reactions and dietary obesity.
Conclusions:
- The sweet taste-induced CPIR is neurally mediated by the peripheral autonomic nervous system, independent of gastrointestinal hormones.
- CPIR plays a significant physiological role in maintaining normal oral glucose tolerance.
- Dysregulation of CPIR may contribute to maladaptive eating behaviors and the development of obesity.
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