• Publications
  • Influence
Cellular mechanisms of insulin resistance.
  • G. Shulman
  • Biology
    The Journal of clinical investigation
  • 15 January 2000
It is shown that commonly accepted models that attempt to explain the association of insulin resistance and obesity are incompatible with recent findings and an alternative model is proposed that appears to fit these and other available data.
Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity
Altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders.
Mechanism by Which Fatty Acids Inhibit Insulin Activation of Insulin Receptor Substrate-1 (IRS-1)-associated Phosphatidylinositol 3-Kinase Activity in Muscle*
The hypothesis that an increase in plasma fatty acid concentration results in a increase in intracellular fatty acyl-CoA and DAG concentrations, which results in activation of PKC-θ leading to increased IRS-1 Ser307 phosphorylation is supported.
Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes.
The hypothesis that insulin resistance in the skeletal muscle of insulin-resistant offspring of patients with type 2 diabetes is associated with dysregulation of intramyocellular fatty acid metabolism is supported, possibly because of an inherited defect in mitochondrial oxidative phosphorylation.
Disruption of IRS-2 causes type 2 diabetes in mice
It is shown that disruption of IRS-2 impairs both peripheral insulin signalling and pancreatic β-cell function, indicating that dysfunction of IRS-2 may contribute to the pathophysiology of human type 2 diabetes.
Mitochondrial Dysfunction in the Elderly: Possible Role in Insulin Resistance
Elderly study participants were markedly insulin-resistant as compared with young controls, and this resistance was attributable to reduced insulin-stimulated muscle glucose metabolism, which supports the hypothesis that an age-associated decline in mitochondrial function contributes to insulin resistance in the elderly.
Type 2 diabetes mellitus
The greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications.
AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation
By sensing the energy status of the muscle cell, AMPK is a critical regulator involved in initiating mitochondrial biogenesis and abrogated GPA-induced increases in the expression of peroxisome proliferator-activated receptor γ coactivator 1α and calcium/calmodulin-dependent protein kinase IV.