We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Effects of Intranasally Administered Insulin and Gangliosides on Hypothalamic Signaling and Expression of Hepatic Gluconeogenesis Genes in Rats with Type 2 Diabetes Mellitus.
- Authors
Zakharova, I. O.; Bayunova, L. V.; Derkach, K. V.; Ilyasov, I. O.; Morina, I. Yu.; Shpakov, A. O.; Avrova, N. F.
- Abstract
The insulin signaling system in hypothalamic neurons plays an important role in the central regulation of glucose metabolism, feeding behavior, and tissue sensitivity to insulin. A decrease in the brain insulin level in metabolic disorders, including diabetes, is the cause of low activities of the key protein kinases regulated through the insulin signaling system. Insulin deficiency in the brain can be compensated by intranasal insulin administration, which allows a direct hormone delivery to the brain. The efficacy of this method can be increased by insulin co-administration with substances enhancing its effects in the brain, such as complex glycosphingolipids, including gangliosides. This work was aimed to study the effects of separate versus combined intranasal administration of insulin (0.5 IU/rat/day) and gangliosides (6 mg/kg/day) to Wistar rats with experimental type 2 diabetes mellitus (DM2) on the activity of key components of insulin signaling in the hypothalamus (Akt, GSK-3β, ERK1/2, p70S6K, AMPK), as well as on the expression of genes responsible for glucose metabolism in the liver (GLUT2, FASN, PCK, G6PC, FBP). It was found that intranasal co-administration of insulin and gangliosides to rats with DM2 restored glucose tolerance, improved tissue insulin sensitivity, enhanced metabolic processes, and inhibited gluconeogenesis in hepatocytes. This occurs largely due to the central synchronized effect of insulin and gangliosides on the functional activity of key insulin signaling proteins in the hypothalamus (GSK3β, p70S6K, ERK1/2, AMPK), as well as BDNF expression recovery and a decrease in mRNA levels of the proinflammatory cytokine IL-1β in hypothalamic neurons. Thus, intranasal co-administration of insulin and gangliosides to rats with DM2 restores to a large extent hypothalamic insulin signaling and the control over hepatic gluconeogenesis, impaired under conditions of diabetic pathology.
- Subjects
HYPOTHALAMUS; TYPE 2 diabetes; GANGLIOSIDES; GENE expression; INSULIN; GLUCONEOGENESIS
- Publication
Journal of Evolutionary Biochemistry & Physiology, 2022, Vol 58, Issue 6, p1744
- ISSN
0022-0930
- Publication type
Article
- DOI
10.1134/S0022093022060072