Key result
Hyperinsulinemic/hypoglycemic clamp significantly increased Fos positive cells in the PVN (191 vs 66) compared to controls, an effect prevented by maintaining euglycemia.
Why the study?
Does maintaining euglycemia prevent insulin-induced Fos expression in brain autonomic regulatory circuits in rats?
Does maintaining euglycemia prevent insulin-induced Fos expression in brain autonomic regulatory circuits in rats?
Absolute Event Rate: 191% vs 66%
Neuronal activation in autonomic regulatory nuclei following insulin administration is driven by hypoglycemia rather than a direct effect of insulin.
Hypoglycemia, not insulin, drives autonomic neuronal activation in rats; leaves open translation to human hypoglycemia unawareness or insulin therapy.
OBJECTIVE: Insulin-induced hypoglycemia activates neurons in hypothalamic and brain medullary nuclei involved in central autonomic regulation. We investigated whether these central neuronal activations relates to a deficiency of glucose supply. METHODS: Three groups of non-fasted, conscious rats received intravenous (iv) saline infusion (control), a hyperinsulinemic/hypoglycemic clamp, or a hyperinsulinemic/euglycemic clamp for 120 minutes and then the brains were collected for Fos immunohistochemistry. RESULTS: The number of Fos positive cells significantly increased in the paraventricular nucleus of the hypothalamus (PVN, 191 +/- 63 versus 66 +/- 18), pontine locus coeruleus (LC, 53 +/- 19 versus 5 +/- 2), brain medullary dorsal motor nucleus of the vagus (DMV, 26 +/- 4 versus 1 +/- 0), and nucleus tractus solitarii (NTS, 38 +/- 3 versus 10 +/- 35) in rats with hyperinsulinemic/hypoglycemic clamp compared with the controls. Maintaining blood glucose levels within physiological range by hyperinsulinemic/euglycemic clamp prevented insulin infusion-induced Fos expression in the PVN, DMV, and NTS. The numbers of Fos positive cells in these nuclei were significantly lower (-87%, -75%, and -51%, respectively) than that in the hypoglycemic rats. CONCLUSION: These results indicate that neuronal activation in hypothalamic and medullary autonomic regulatory nuclei induced by insulin administration is caused by hypoglycemia rather than a direct action of insulin. In addition, certain neurons in the medullary DMV and NTS respond to declines in glucose levels within physiological range.
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Ao et al. (2005) studied Insulin-induced hypoglycemia. Hyperinsulinemic/hypoglycemic clamp vs. Intravenous saline infusion was evaluated on Number of Fos positive cells in the paraventricular nucleus of the hypothalamus (PVN). Hyperinsulinemic/hypoglycemic clamp significantly increased Fos positive cells in the PVN (191 vs 66) compared to controls, an effect prevented by maintaining euglycemia.
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