The Brain Adenylyl Cyclase Signaling System and Cognitive Functions in Rats with Neonatal Diabetes under the Influence of Intranasal Serotonin

Abstract

Now insulin is commonly accepted as drug to be used in treatment of T1DM as well as T2DM, especially when β cell function falls [12]. Usually, insulin is injected subcutaneously, but recently the other ways of delivery of hormone and its analogues, such as oral and intranasal,

The Functional State of Hormone-Sensitive Adenylyl Cyclase Signaling System in Diabetes Mellitus

“…In our experiments, no alterations of the sensitivity of AC system in the brain of STZ rats to selective agonists of G s -coupled 5-HT 6 R were detected, while AC sensitivity to agonists of G i -coupled 5-HT 1A R and 5-HT 1B R was decreased significantly [32, 33, 35, 41]. In the brain of rats with prolonged T1DM and neonatal T2DM, the AC inhibitory effects of 5-HT 1B R-agonist 5-nonyloxytryptamine were reduced by 79 and 70%, respectively.…”

“…The AC inhibitory effect of DA 2 R agonist bromocriptine and its stimulating effect on 5′ guanylylimidodiphosphate (GppNHp) binding of G i proteins in the synaptosomal membranes isolated from the brain of diabetic rats were decreased, predominantly in T1DM [32, 34, 35]. As the binding characteristics of DARs and the catalytic activity of AC did not change essentially, a suggestion was made that the impairment of bromocriptine-induced AC inhibition in the diabetic brain was due to the reduced function of G i proteins [36].…”

“…In the brain of rats with prolonged T1DM and neonatal T2DM, the AC inhibitory effects of 5-HT 1B R-agonist 5-nonyloxytryptamine were reduced by 79 and 70%, respectively. The increase of GppNHp binding of G proteins induced by 5-nonyloxytryptamine and nonselective 5-HT 1 R agonist 5-methoxy- N , N -dimethyltryptamine in the case of the neonatal model of T2DM was reduced by 57 and 51%, respectively [35, 41]. In our view, the weakening of 5-HT 1 R-mediated signaling may be associated with a decrease of expression and activity of G i proteins, because in the diabetic brain the impairment of other G i -coupled cascades was also detected.…”

Brain Signaling Systems in the Type 2 Diabetes and Metabolic Syndrome: Promising Target to Treat and Prevent These Diseases

“…This is confirmed by the results of treatment of patients with depression using selective serotonin reuptake inhibitors (SSRIs). Treatment with fluoxetine decreased body weight, normalized the glucose level, reduced the blood level of glycosylated hemoglobin, improved the insulin sensitivity, as well as prevented neurological disorders [34,40,258–262]. We showed that the long-term treatment of female rats with neonatal model of T2DM using intranasally administered 5-HT improved metabolic parameters and cognitive functions, and restored the insulin sensitivity [34].…”

“…Treatment with fluoxetine decreased body weight, normalized the glucose level, reduced the blood level of glycosylated hemoglobin, improved the insulin sensitivity, as well as prevented neurological disorders [34,40,258–262]. We showed that the long-term treatment of female rats with neonatal model of T2DM using intranasally administered 5-HT improved metabolic parameters and cognitive functions, and restored the insulin sensitivity [34]. According to the other authors, the treatment of obese glucose-intolerant mice with selective 5-HT 2C R-agonist BVT.X significantly improved glucose tolerance and reduced the plasma insulin level; these effects were observed at the BVT.X concentration ineffective in respect of feeding behavior, energy expenditure, body weight and locomotor activity [40].…”