To determine whether obesity-associated hyperinsulinemia promotes bone growth by activating the insulin receptor in the growth plate, we generated <sup>TamCart</sup>IR<sup>flox/flox</sup> mice.
This is a highly significant observation because it is the first to show that systemic hyperinsulinemia can suppress autophagy in IR-deficient hearts through IGF-1R signaling.
Acute induction of insulin receptor knockout in adipocytes changed the substrate preference to fat before induction of a diabetic phenotype including hyperinsulinaemia and hyperglycaemia.
Additionally, both mRNA expressions and protein levels of insulin increased significantly in the 10 and 100 μg/L exposure groups, while transcription levels of genes encoding insulin receptor substrates decreased significantly in these groups, indicating a possibly decreased insulin sensitivity due to impairment of insulin signaling transduction downstream of insulin receptor.
Both acute and chronic exposure of MC-LR, even at very low concentrations (1 μg/L), impaired the insulin receptor signalling pathway and induced hyperinsulinemia and insulin resistance in mice.
The combination of fasting hyperinsulinemia with acanthosis nigricans in a lean subject with hypoglycemia suggests severe insulin resistance and warrants INSR gene screening.
These podocytes lose expression of the IR as a direct consequence of prolonged exposure to high insulin concentrations, which causes an increase in IR protein degradation via a proteasome-dependent and bafilomycin-sensitive pathway.
We concluded that vitamin D3 ameliorated insulin resistance and hyperinsulinemia in diabetic rat model received HFW through reduction of IDE and activation of insulin receptor phosphorylation.
The expression of the insulin receptor (IR) signaling cascade, including IR, IR substrate, phosphatidylinositol 3-kinase, Akt, and glucose transporter 4, was inhibited both in the skeletal muscle and the liver, which might be a main reason for the hyperglycemia and hyperinsulinemia.
TRG (50 mg/kg; p.o) lowered serum glucose, fructosamine, insulin, and HOMA-IR index and increased insulin sensitivity in soleus muscle via augmenting insulin receptor autophosphorylation (IR-PH), pT308-Akt, and glucose transporter 4 (GLUT4).
A 29-year-old woman developed an autoantibody to the insulin receptor (type B insulin resistance), causing extreme insulin resistance and hyperinsulinemia.
IL-1β and insulin increased the uptake of glucose into macrophages, and insulin reinforced a pro-inflammatory pattern via the insulin receptor, glucose metabolism, production of reactive oxygen species, and secretion of IL-1β mediated by the NLRP3 inflammasome.
Donohue syndrome ([DS]; leprechaunism) describes a genetic autosomal recessive disorder that results from the presence of homozygous or compound heterozygous mutations in the insulin receptor gene (INSR; 19p13.3-p13.2).Donohue syndrome is associated with a fatal congenital form of dwarfism with features of intrauterine and postnatal growth retardation, exaggerated hyperglycemia with hyperinsulinism and dysmorphic abnormalities.We present a case of DS owing to the rarity of this syndrome (1 case in every million births).
The data in this paper demonstrate that IR knockdown in primary tumors partially reverses the growth-promoting effects of hyperinsulinemia as well as highlighting the importance of the insulin receptor signaling pathway in cancer progression, and more specifically in epithelial-mesenchymal transition.
We characterised expression of IR-related molecules, IRS-1 phosphorylation and downstream signalling in a panel of 5 colon cancer cell lines at different insulin exposures: 15 min (100 nM), approximating to acute stimulation; 48 h (100 nM), used to demonstrate adaptive changes; and 12 weeks (20 nM; chronic insulin exposure, CIE), approximating to chronic hyperinsulinaemia.
Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance.
Using RT-PCR, we found that visfatin did not regulate IR expression and that an increased insulin release was also unlikely to be involved because insulin was unable to increase PGE(2) release.