Prospects for the Use of Intranasally Administered Insulin and Insulin-Like Growth Factor-1 in Cerebral Ischemia.

Current approaches to the treatment of stroke have significant limitations, and neuroprotective therapy is ineffective. In view of this, searching for effective neuroprotectors and developing new neuroprotective strategies remain a pressing topic in research of cerebral ischemia. Insulin and insulin-like growth factor-1 (IGF-1) play a key role in the brain functioning by regulating the growth, differentiation, and survival of neurons, neuronal plasticity, food intake, peripheral metabolism, and endocrine functions.

Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium.

A decrease in the activity of the insulin signaling system of the brain, due to both central insulin resistance and insulin deficiency, leads to neurodegeneration and impaired regulation of appetite, metabolism, endocrine functions. This is due to the neuroprotective properties of brain insulin and its leading role in maintaining glucose homeostasis in the brain, as well as in the regulation of the brain signaling network responsible for the functioning of the nervous, endocrine, and other systems. One of the approaches to restore the activity of the insulin system of the brain is the use of intranasally administered insulin (INI).

Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury.

Clinical trials show that insulin administered intranasally is a promising drug to treat neurodegenerative diseases, but at high doses its use may result in cerebral insulin resistance. Identifying compounds which could enhance the protective effects of insulin, may be helpful to reduce its effective dose. Our aim was thus to study the efficiency of combined use of insulin and α-tocopherol (α-T) to increase the viability of cultured cortical neurons under oxidative stress conditions and to normalize the metabolic disturbances caused by free radical reaction activation in brain cortex of rats with two-vessel forebrain ischemia/reperfusion injury.

The effect of metformin treatment on the basal and gonadotropin-stimulated steroidogenesis in male rats with type 2 diabetes mellitus.

Type 2 diabetes mellitus impairs reproductive functions in men, and important tasks are deciphering the mechanisms of testicular dysfunctions in diabetes and the search of effective approaches to their correction. The purpose was to study the effect of four-week metformin treatment (120 mg kg  day ) of male Wistar rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes on basal and gonadotropin-stimulated steroidogenesis, intratesticular content of leptin and the leptin and luteinising hormone receptors and on spermatogenesis. Diabetic rats had hyperleptinaemia, androgen deficiency and reduced sperm count and quality, and in the testes, they had the increased leptin level and the decreased content of the leptin and luteinising hormone receptors and 17-hydroxyprogesterone.

The Protective Effect of Insulin on Rat Cortical Neurons in Oxidative Stress and Its Dependence on the Modulation of Akt, GSK-3beta, ERK1/2, and AMPK Activities.

Insulin is a promising drug for the treatment of diseases associated with brain damage. However, the mechanism of its neuroprotective action is far from being understood. Our aim was to study the insulin-induced protection of cortical neurons in oxidative stress and its mechanism.

The evidence of metabolic-improving effect of metformin in Ay/a mice with genetically-induced melanocortin obesity and the contribution of hypothalamic mechanisms to this effect.

In diet-induced obesity, metformin (MF) has weight-lowering effect and improves glucose homeostasis and insulin sensitivity. However, there is no information on the efficiency of MF and the mechanisms of its action in melanocortin-type obesity. We studied the effect of the 10-day treatment with MF at the doses of 200, 400 and 600 mg/kg/day on the food intake and the metabolic and hormonal parameters in female C57Bl/6J (genotype Ay/a) agouti-mice with melanocortin-type obesity, and the influence of MF on the hypothalamic signaling in obese animals at the most effective metabolic dose (600 mg/kg/day).