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[FUNCTIONAL STATE OF THE HYPOTHALAMIC SIGNALING SYSTEMS IN RATS WITH TYPE 2 DIABETES MELLITUS TREATED WITH INTRANASAL
Zhurnal Evoliutsionnoi Biokhimii I Fiziologii
|January 30, 2019
Summary
Intranasal insulin (II) treatment improved glucose control and restored hypothalamic signaling in diabetic rats. This suggests II may enhance insulin sensitivity and energy metabolism by modulating key neurotransmitter pathways.
Area of Science:
- Endocrinology
- Neuroscience
- Metabolic Disorders
Background:
- Intranasal insulin (II) is used for cognitive disorders but its mechanisms in type 2 diabetes mellitus (DM2) are unclear.
- The effect of II on hypothalamic signaling, crucial for energy metabolism, requires further investigation.
- Understanding II's impact on DM2 could reveal new therapeutic strategies.
Purpose of the Study:
- To investigate the effects of five-week intranasal insulin (II) treatment on metabolic parameters in a neonatal rat model of type 2 diabetes mellitus (DM2).
- To assess the functional activity of hypothalamic signaling systems, including melanocortin, dopamine, and serotonin pathways, following II treatment in DM2 rats.
Main Methods:
- Male rats with a neonatal model of DM2 were treated with intranasal insulin (0.48 IU/rat) for five weeks.
- Metabolic parameters (plasma glucose, glucose tolerance, utilization) were measured.
- Hypothalamic adenylyl cyclase (AC) activity and gene expression of relevant receptors (MC4R, D2-DAR, 5-HT1BR, insulin receptor, IRS2) were analyzed.
Main Results:
- II treatment normalized plasma glucose, restored glucose tolerance and utilization in diabetic rats.
- II normalized the regulatory effects of MC4R, D2-DAR, and 5-HT1BR agonists on hypothalamic AC activity.
- II increased 5-HT1BR and MC4R gene expression, while attenuating D1-DAR agonist effects and decreasing Drdl gene expression.
Conclusions:
- Intranasal insulin (II) partially restores hypothalamic AC signaling pathways regulated by melanocortins, serotonin, and dopamine in a neonatal type 2 diabetes mellitus (DM2) rat model.
- These restored signaling pathways represent a potential mechanism for II's positive influence on energy metabolism and peripheral insulin sensitivity.
- II treatment offers a promising therapeutic avenue for managing metabolic dysregulation in type 2 diabetes mellitus.
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