Our results also provide a mechanistic explanation for the functional link between hyperinsulinemia and p27 loss in the pathogenesis of endometrial epithelial hyperplasia in PCOS patients.
Reduced GLP-1 levels are observed in obesity and type 2 diabetes mellitus (T2DM) and are associated with reduced insulin secretion and increased insulin resistance.
Intraperitoneal administration of lamprey and paddlefish GLP-1 (25 nmol/kg body weight) in mice produced significant decreases in blood glucose and increased insulin concentrations comparable to the effects of human GLP-1.
Remarkably, we also noted a trend toward an increased insulin response to GLP-1 in carriers of MTNR1B (P = 0.03), which may offer new therapeutic possibilities.
In this study, we show that hyperinsulinemia in the Rag/MKR mice increases the expression of mesenchymal transcription factors, TWIST1 and ZEB1, and increases the expression of the angiogenesis marker, vascular endothelial growth factor A (VEGFA).
Using mRNA sequencing (mRNA-Seq), we show that unconventional Xbp1 mRNA splicing is required to increase and decrease the expression of several hundred mRNAs encoding functions that expand the protein secretory capacity for increased insulin production and protect from oxidative damage, respectively.
We speculate that the appearance of vimentin-positive islet cells may reflect induction of differentiation in response to the increased insulin demand, and vimentin may serve as an early marker of endocrine pancreas disorders.
Endometrial VEGFA was significantly decreased after treatment with high insulin in vivo and in vitro (p<0.05), whereas ANG-1 and TIE2 expression was significantly increased (p<0.05).
These results suggest that administration of BCAA may downregulate VEGF expression in patients who have hyperinsulinemia and are in the process of developing HCC.
In this study, we show that hyperinsulinemia in the Rag/MKR mice increases the expression of mesenchymal transcription factors, TWIST1 and ZEB1, and increases the expression of the angiogenesis marker, vascular endothelial growth factor A (VEGFA).
Our in vitro and in vivo findings show that vascular cell adhesion molecule-1 activation cannot be due to hyperinsulinaemia.[Diabetologia (1999) 42: 1235-1239]
In parallel, the VAMP8 null mice also had fasting hypoglycemia (84 ± 11 vs. 115 ± 4) and enhanced glucose tolerance with increased insulin sensitivity due to increases in both basal and insulin-stimulated glucose uptake in skeletal muscle (0.19 ± 0.04 vs. 0.09 ± 0.01 mmol/kg/min during basal, 0.6 ± 0.04 vs. 0.31 ± 0.06 mmol/kg/min during clamp in red-gastrocnemius muscle, P < 0.05).