Insulin administered intranasally, but not proinsulin C-peptide, normalises hormonal parameters and hypothalamic gene expression in male rats with type 2 diabetes and obesity
DOI:
https://doi.org/10.33910/2687-1270-2022-3-1-41-57Keywords:
insulin, proinsulin C-peptide, intranasal administration, type 2 diabetes, obesity, hyperinsulinemia, hypothalamus, leptin, glucose tolerance, thyroid statusAbstract
Type 2 diabetes mellitus (DM2) is characterised by changes in brain signalling systems, including those regulated by insulin. Intranasally administered insulin (II) can be used to restore brain insulin signalling. The effectiveness of II, as we have shown earlier in DM1 and insulin-deficient DM2, increases when combined with intranasally administered C-peptide (IC). The aim of this work was to study the effect of a 9-day treatment of rats with diet-induced DM2, obesity and hyperinsulinemia with II (0.5 IU/rat/day) and combined II and IC (36 μg/rat/day) on rats’ metabolic parameters, basal and glucose-stimulated levels of insulin, adipokines, glucagon-like peptide-1 and ghrelin, hormonal status of the thyroid and gonadal systems, intrahypothalamic insulin and leptin levels, and expression of hypothalamic genes encoding receptors and nutritional factors. II monotherapy normalised hypothalamic insulin levels lowered in DM2, improved glucose homeostasis, thyroid status and insulin, leptin and incretin responses to glucose, restored the expression of hypothalamic proopiomelanocortin and M4-melanocortin receptor genes responsible for reducing appetite, and reduced the gene expression of orexigenic neuropeptide Y. The combined use of II and IC did not improve the effect of II. IC monotherapy was ineffective and even worsened subject metabolic parameters. Thus, in DM2 rats with hyperinsulinemia, II improved metabolic and hormonal parameters. This is due to normalisation of the brain insulin levels that had been reduced as a result of weaker receptor-mediated transport of insulin across the blood-brain barrier. IC, however, was ineffective, including in combination with II.
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