Chronic exposure to free fatty acids (FFAs) may induce β cell apoptosis in type 2 diabetes. However, the precise mechanism by which FFAs trigger β cell apoptosis is still unclear. Tribbles homolog 3 (TRB3) is a pseudokinase inhibiting Akt, a key mediator of insulin signaling, and contributes to insulin resistance in insulin target tissues. This paper outlined the role of TRB3 in FFAs-induced IN...

Myo-Inositol (Ins; see Fig. 1 ), one of nine distinct cyclohexanehexol isomers, is an essential dietary requirement for the growth of mice (Woolley, 1940) and is greatly concentrated in the milk of lactating mammals (Burton & Wells, 1974, 1976). Although not strictly a vitamin, as it can be synthesized from glucose by many eukaryotic cells (Eisenberg, 1967), yeast mutants which lack this synthe...

Inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] originating in the vascular smooth-muscle cells (VSMCs) has been shown to modulate the Ca(2+) stores in endothelial cells (ECs). However, the reverse is not found, suggesting that Ins(1,4,5)P(3) movement might be unidirectional across gap junctions at the myoendothelial junction (MEJ), or that distribution of the Ins(1,4,5)P(3) receptor [Ins(1,4,5...

Proglucagon is processed differentially in pancreatic alpha-cells and intestinal endocrine L cells to release either glucagon or glucagon-like peptide-1-(7-36amide) (tGLP-1), two peptide hormones with opposing biological actions. Previous studies have demonstrated that the prohormone convertase PC2 is responsible for the processing of proglucagon to glucagon, and have suggested that the related...

BACKGROUND Corticosteroid-resistant idiopathic nephrotic syndrome (INS) recurs rapidly after transplantation in 30% to 50% of transplant recipients, suggesting the presence of 1 or more circulating factors that alter the glomerular filtration barrier. We investigated the possible role in INS recurrence of soluble ST2 (sST2) protein, a marker of T helper type 2 (T(H)2) cells and a factor predict...

Hedgehogs (Hhs) are intercellular signaling molecules that regulate tissue patterning in mammalian development. Mammalian Hhs include Sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh). The absence of Shh expression is required for the early development of the endocrine and exocrine pancreas, but whether Hh signaling functions in the fully developed adult endocrine pancreas ...

In islet beta-cells and INS-1 cells both the high activity of malic enzyme and the correlation of insulin secretion rates with pyruvate carboxylase (PC) flux suggest that a pyruvate-malate cycle is functionally relevant to insulin secretion. Expression of the malic enzyme isoforms in INS-1 cells and rat islets was measured, and small interfering RNA was used to selectively reduce isoform mRNA e...

Mitochondria-mediated production of reactive oxygen species (ROS) plays a key role in apoptosis. Mitochondrial phospholipid cardiolipin molecules are likely the main target of ROS because they are particularly rich in polyunsaturated fatty acids. They are also located in the inner mitochondrial membrane near the ROS-producing sites. Under physiological conditions mitochondria can repair peroxid...

Pancreatic β cell dysfunction and reduction due to glucose toxicity play a crucial role in the development of type 2 diabetes mellitus (T2DM). Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose tissue, thereby enhancing thermogenesis and increasing energy expenditure. Recent studies have repo...

OBJECTIVES Glucose fluctuations are both strong predictor of diabetic complications and crucial factor for beta cell damages. Here we investigated the effect of intermittent high glucose (IHG) on both cell apoptosis and proliferation activity in INS-1 cells and the potential mechanisms. METHODS Cells were treated with normal glucose (5.5 mmol/L), constant high glucose (CHG) (25 mmol/L), and I...