Insulin resistance is a common finding in hypertensive humans and animal models. The Dahl salt-sensitive (S) rat is an ideal model of genetically predetermined insulin resistance and salt-sensitive hypertension. Along the insulin signaling pathway, the insulin receptor substrates 1 and 2 (IRS-1 and -2) are important mediators of insulin signaling. IRS-1 and/or IRS-2 genetic variant(s) and/or en...

The insulin receptor substrate (IRS) proteins are key mediators of insulin and insulinlike growth factor 1 (IGF-1) signaling. Protein tyrosine phosphatase (PTP)-1B dephosphorylates and inactivates both insulin and IGF-1 receptors. IRS2-deficient mice present altered hepatic insulin signaling and β-cell failure and develop type 2-like diabetes. In addition, IRS2 deficiency leads to developmental...

The dysregulation of glucose-inhibited glucagon secretion from the pancreatic islet α-cell is a critical component of diabetes pathology and metabolic disease. We show a previously uncharacterized [Ca(2+)]i-independent mechanism of glucagon suppression in human and murine pancreatic islets whereby cAMP and PKA signaling are decreased. This decrease is driven by the combination of somatostatin, ...

Neuronal cell death is an early pathological feature of diabetic retinopathy. We showed previously that insulin receptor signaling is diminished in retinas of animal models of diabetes and that downstream Akt signaling is involved in insulin-mediated retinal neuronal survival. Therefore, further understanding of the mechanisms by which retinal insulin receptor signaling is regulated could have ...

Obesity-induced inflammation plays an important role in the development of insulin resistance, type 2 diabetes (T2D), and metabolic dysfunctions. Chronic activation of proinflammatory pathways within insulin target cells can lead to obesity-related insulin resistance. The inflammatory mediators consist of immune cells, cytokines, adipokines, and inflammatory signaling molecules. Targeting obesi...

Growth factor receptor binding protein 10 (Grb10) has been identified as a cellular partner of a number of receptor tyrosine kinases and other signaling mediators, compatible with multiple roles in mitogenic, metabolic, and embryogenic signaling that are also supported by the tissue distribution of Grb10. In particular, a role has been implicated in the regulation of PI 3-kinase signaling downs...

Acromegaly is associated with cardiac hypertrophy, which is believed to be a direct consequence of chronically elevated GH and IGF1. Given that insulin is important for cardiac growth and function, and considering that GH excess induces hyperinsulinemia, insulin resistance, and cardiac alterations, it is of interest to study insulin sensitivity in this tissue under chronic conditions of elevate...

A lthough there are different mechanistic theories for aging, endothelial dysfunction (ED) is a rather neglected player in the aging process. A maladaptive insulin/IGF-1-like signaling (IIS) has a remarkable importance in proaging mechanisms, and insulin has direct effects on ED. Therefore, we assume that the endothelium plays a key role in mediating the aging process in the presence of maladap...

Prostate cancer (PCa) is the most common type of cancer among men over 60 years old. The aggressiveness and mortality of PCa can be correlated with obesity. Adipose tissue-derived cytokines such as adiponectin may explain the correlation between PCa and obesity. Since the correlation between adiponectin and aggressive PCa is still not fully evaluated, we aimed to investigate the probable role o...