Intranasal Insulin Restores Metabolic Parameters and Insulin Sensitivity in Rats with Metabolic Syndrome

Abstract

We studied the effect of 10-week treatment with intranasal insulin (0.5 IU/day) on glucose tolerance, glucose utilization, lipid metabolism, functions of pancreatic β cells, and insulin system in the liver of rats with cafeteria diet-induced metabolic syndrome. The therapy reduced body weight and blood levels of insulin, triglycerides, and atherogenic cholesterol that are typically increased in metabolic syndrome, normalized glucose tolerance and its utilization, and increased activity of insulin signaling system in the liver, thus reducing insulin resistance. The therapy did not affect the number of pancreatic islets and β cells. The study demonstrates prospects of using intranasal insulin for correction of metabolic parameters and reduction of insulin resistance in metabolic syndrome.

Inflammation and Insulin Resistance as Risk Factors and Potential Therapeutic Targets for Alzheimer’s Disease

“…The common doses of IN insulin range from 20 to 160 IU according to different studies, with different outcomes even though there is a growing consensus that IN administration is able to promote changes on CNS as well as peripheral pathways. There are many positive metabolic effects of IN insulin such as body weight management, food intake and fat composition, with variations according to sex, age and protocol of administration (Derkach et al, 2017). However, in this review we will focus on cognitive-related outcomes.…”

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

“…It may be emphasized that in order to reveal the additive effect of insulin and α-T, we applied much lower doses of these drugs than are usually used when studying their protective effects in vivo. Effects of insulin administered intranasally to rats are usually studied using its dose of 0.5 IU/rat [ 51 , 52 ]. As far as α-T is concerned, administration of 125 or even 250 mg/kg of this compound to rats orally is used frequently when studying the protection elicited by a single or multiple administration of this drug [ 53 , 54 ].…”

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

“…The effective doses of INI used by us are comparable to those for intracerebroventricular administration of the hormone. In this regard, it is noteworthy that INI at doses of 0.25–0.5 IU/rat clearly restored the metabolic and hormonal parameters, as well as cognitive functions, in rats with experimental models of DM [ 206 , 207 , 208 , 209 ] and MS [ 210 ]. Our studies on the effects of INI in DM and MS open up prospects for stroke prevention in patients with these diseases, as well as in patients who have undergone cerebral ischemia.…”

“…We have shown that administration of low doses of INI (0.25–1.5 IU/rat) to rats with models of T1DM, T2DM, and MS, with different durations, leads to an improvement in their metabolic and hormonal parameters and improved cognitive functions, and in the case of severe form of T1DM, such treatment increases the survival of animals [ 206 , 208 , 209 , 210 , 296 , 297 , 298 , 299 , 300 , 301 , 302 ]. Treatment of diabetic rats with INI moderately reduced hyperglycemia without causing hypoglycemic episodes, attenuated hyperphagia, and in the case of T2DM and diet-induced MS, INI increased tissue sensitivity to insulin and leptin and normalized glucose tolerance [ 207 , 210 , 302 ]. These effects were associated with partial restoration in the hypothalamic signaling pathways regulated by peptide neurohormones and biogenic amines (serotonin and dopamine), as well as with inhibition of apoptotic processes in the brain [ 209 , 301 , 302 ].…”