![]() Adult patients with T1D, who experience hyper- and hypoglycemic episodes, have a six-fold greater risk for the development of dementia compared to those without these complications. Chronic diabetic conditions progressively diminish glucose transport, which leads to impaired brain growth and cognitive development in children with T1D. Nevertheless, in the brain, GLUT4 activation regulates glucose sensing and glucose tolerance in conjunction with other glucose transporters in the brain. Among them, glucose transporter 1 (GLUT1) is the major transporter for glucose in the brain. The fundamental difference between the glucose supply in the nervous and peripheral tissues is the utilization of over nine different glucose transporters compared to the major insulin-regulated GLUT4 in peripheral adipose and muscle tissues. The brain utilizes 25% of the total metabolic glucose for energy. Insufficient control over the action of therapeutic insulin is now considered as a major reason behind its adverse effects (reviewed in ). Normoinsulinemia supports cognition, whereas both hypoinsulinemia and, particularly, supraphysiological concentrations of insulin impair cognition and worsen dementia pathology. ![]() ![]() Insulin impedes the cleavage of beta amyloid by the insulin-degrading enzyme in the brain, resulting in the formation of amyloid aggregates, and an increased tau phosphorylation. One of the major complications of diabetes is the damage of nervous tissue. However, various non-glycemic adverse effects (reviewed in ), including insulin-induced vasodilation, changes in vascular permeability, and sodium retention contribute to the low therapeutic index of insulin, calculated as a ratio of beneficial to adverse effects. This study demonstrates that the flexible nanofiber AAC2 can serve as a therapeutic platform for the combinatorial treatment of diabetes and its complications.Ĭurrent strategies to improve control over insulin action follow three major directions: (1) identifying insulinotropic hormones, (2) modifying the structure of insulin to improve its tissue specific responses and efficacy, and (3) creating polymers and microdevices capable of releasing insulin in response to elevated blood glucose. Consequently, treatment with AAC2-hINS markedly advanced both physical and cognitive performance in mice with STZ-induced and genetic type 1 diabetes compared to treatments with free AAC2 or hINS. Mice treated with the AAC2-hINS complex were devoid of hypoglycemic episodes, had improved levels of insulin in circulation and in the brain, and increased expression of neurotransmitter taurine transporter, Slc6a6. AAC2-hINS acted as a complex and exhibited different properties compared to free AAC2 or hINS. Free AAC2, free human insulin (hINS) and AAC2-bound-human insulin (AAC2-hINS) were tested in streptozotocin (STZ)-induced mouse model of type 1 diabetes. Here, we compare the effects of free insulin to insulin bound to positively charged nanofibers comprised of self-assembling amino acid compounds (AACs) with an antioxidant-modified side chain moiety (AAC2) in both in vitro and in vivo models of type 1 diabetes. Supramolecular nanostructures provide a flexible strategy for combinatorial regulation of glycemia. Diabetes poses a high risk for debilitating complications in neural tissues, regulating glucose uptake through insulin-dependent and predominantly insulin-independent pathways.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |