Insulin Receptor Signaling in Normal and Insulin-Resistant States

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

“…The phosphorylated insulin receptor then initiates a cascade of phosphorylation events: first, Insulin Receptor Subunit-1 (IRS-1), followed in succession by Phosphoinositol 3′-kinase (PI 3′-kinase) 3-Phophoinositide-Dependent Protein Kinase-1 (PDK-1), Protein Kinase B (Akt/PKB), and then atypical Protein Kinase C (PKC). The result of this insulin-dependent phosphorylation cascade is glucose translocation and/or glucose transporter synthesis [105]. In addition to its role in glucose metabolism, insulin also affects cell growth, gene expression, and the synthesis of proteins, lipids, and glycogen.…”

The Inactivation of RabGAP Function of AS160 Promotes Lysosomal Degradation of GLUT4 and Causes Postprandial Hyperglycemia and Hyperinsulinemia

“…Microcystin-LR was from Enzo Life Sciences (Farmingdale, NY). 2-Deoxy-D- [1,[2][3] The AS160 KO-first ES cells (Tbc1d4tm1a(EUCOMM)Hmgu, clone no. HEPD0601_5_F08) were purchased from the European Mouse Mutant Cell Repository (Neuherberg, Germany), and used for blastocyst injection to obtain the AS160 f/f mice ( Supplementary Fig.…”

“…Insulin resistance is the key feature of type 2 diabetes mellitus and causes dysregulation of glucose homeostasis in individuals with this disease (1). One of the functions of insulin is to regulate glucose uptake, the mechanism of which is not completely understood despite intensive studies.…”

Myotubes derived from human-induced pluripotent stem cells mirror in vivo insulin resistance

“…Insulin resistance is present in humans with obesity, metabolic syndrome, and T2D, and in the latter can be detected years before the clinical presentation of disease (2,22), suggesting a primary role in the pathophysiology of T2D. Severe forms of insulin resistance are observed in patients with genetic mutations in the insulin receptor or anti-insulin receptor antibodies (1,(23)(24)(25), and these have been highly informative in our understanding of insulin signaling pathways and the impact of insulin resistance on systemic metabolism. The molecular mechanisms underlying insulin resistance in these disorders may include both acquired and genetic components; however, dissecting the relative contributions of each is difficult due to the lack of robust and reliable models for the study of disease pathogenesis in humans in vitro.…”

“…Thus, iPS-derived myotubes from individuals with genetically determined insulin resistance demonstrate many of the defects observed in vivo in insulin-resistant skeletal muscle and provide a new model to analyze the molecular impact of muscle insulin resistance. I nsulin resistance is a central feature of type 2 diabetes (T2D), obesity, and metabolic syndrome (1). Insulin action in skeletal muscle plays a particularly important role as mediator of whole-body glucose disposal, and insulin resistance in skeletal muscle has been identified as an early defect in humans in T2D and a major risk factor for development of T2D in genetically susceptible individuals (2)(3)(4)(5).…”