Pancreatic β-cell dysfunction plays an important role in the pathogenesis of both type 1 and
type 2 diabetes. Insulin, which is produced in β-cells, is a critical regulator of metabolism …

The primary genetic, environmental, and metabolic factors responsible for causing insulin
resistance and pancreatic β-cell failure and the precise sequence of events leading to the …

Glucotoxicity, lipotoxicity, and glucolipotoxicity are secondary phenomena that are proposed
to play a role in all forms of type 2 diabetes. The underlying concept is that once the primary …

The concept of glucolipotoxicity refers to the combined, deleterious effects of elevated
glucose, and fatty acid levels on pancreatic beta-cell function and survival. Significant …

We have proposed the “glucolipotoxicity” hypothesis in which elevated free fatty acids
(FFAs) together with hyperglycemia are synergistic in causing islet β-cell damage because …

Embryonic stem (ES) cells display the ability to differentiate in vitro into a variety of cell
lineages. Using a cell-trapping system, we have obtained an insulin-secreting cell clone …

Malonyl-CoA is an allosteric inhibitor of carnitine palmitoyltransferase (CPT) I, the enzyme
that controls the transfer of long-chain fatty acyl (LCFA)-CoAs into the mitochondria where …

Patients with the metabolic syndrome are characterized by insulin resistance, obesity and a
predisposition to hypertension, dyslipidaemia, pancreatic β-cell dysfunction, type 2 diabetes …

Insulin resistance is a state in which higher than normal concentrations of insulin are
required for normal response. The most common underlying cause is central obesity …

β-Cells possess inherent mechanisms to adapt to overnutrition and the prevailing
concentrations of glucose, fatty acids, and other fuels to maintain glucose homeostasis …