Glucose Responsiveness of β-Cells Depends on Fatty Acids.

Glucose-stimulated insulin secretion (GSIS) is the gold standard for β-cell function. Both experimental and clinical diabetology, i. e.

The Expression of Aldolase B in Islets Is Negatively Associated With Insulin Secretion in Humans.

Context: Reduced β-cell mass, impaired islet function, and dedifferentiation are considered causal to development of hyperglycemia and type 2 diabetes. In human cohort studies, changes of islet cell-specific expression patterns have been associated with diabetes but not directly with in vivo insulin secretion.

Objective: This study investigates alterations of islet gene expression and corresponding gene variants in the context of in vivo glycemic traits from the same patients.

Palmitate and insulin counteract glucose-induced thioredoxin interacting protein (TXNIP) expression in insulin secreting cells via distinct mechanisms.

Glucose and palmitate synergistically stimulate insulin secretion, but chronically elevated they induce apoptotic β-cell death. The glucotoxic effect has been attributed, at least partly, to the upregulation of the oxidative stress marker thioredoxin interacting protein (TXNIP). Palmitate downregulates TXNIP expression, the functional significance of which is still under debate.

Point mutation of Ffar1 abrogates fatty acid-dependent insulin secretion, but protects against HFD-induced glucose intolerance.

Objective: The fatty acid receptor 1 (FFAR1/GPR40) mediates fatty acid-dependent augmentation of glucose-induced insulin secretion (GIIS) in pancreatic β-cells. Genetically engineered Ffar1-knockout/congenic mice univocally displayed impaired fatty acid-mediated insulin secretion, but in vivo experiments delivered controversial results regarding the function of FFAR1 in glucose homeostasis and liver steatosis. This study presents a new coisogenic mouse model carrying a point mutation in Ffar1 with functional consequence.

Metabolic crosstalk between fatty pancreas and fatty liver: effects on local inflammation and insulin secretion.

Aims/hypothesis: Obesity-linked ectopic fat accumulation is associated with the development of type 2 diabetes. Whether pancreatic and liver steatosis impairs insulin secretion is controversial. We examined the crosstalk of human pancreatic fat cells with islets and the role of diabetogenic factors, i.

Protein kinase Cδ regulates nuclear export of FOXO1 through phosphorylation of the chaperone 14-3-3ζ.

Aims/hypothesis: Forkhead box protein O1 (FOXO1) is a transcription factor essential for beta cell fate. Protein kinase B-dependent phosphorylation of FOXO1 at S256 (P-FOXO1) enables its binding to 14-3-3 dimers and nuclear export. Dephosphorylated FOXO1 enters nuclei and activates pro-apoptotic genes.

Mice Lacking Free Fatty Acid Receptor 1 (GPR40/FFAR1) are Protected Against Conjugated Linoleic Acid-Induced Fatty Liver but Develop Inflammation and Insulin Resistance in the Brain.

Background/aims: Conjugated linoleic acids (CLAs) affect body fat distribution, induce insulin resistance and stimulate insulin secretion. The latter effect is mediated through the free fatty acid receptor-1 (GPR40/FFAR1). This study examines whether GPR40/FFAR1 interacts with tissue specific metabolic changes induced by CLAs.

Activation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) by free fatty acid receptor 1 (FFAR1/GPR40) protects from palmitate-induced beta cell death, but plays no role in insulin secretion.

Aims: GPR40/FFAR1 mediates palmitate-induced stimulation of insulin secretion but its involvement in lipotoxicity is controversial. Our previous observations suggest that FFAR1/GPR40 agonists protect against lipotoxicity although the underlying mechanism remains elusive. The present study examines the role of ERK1/2 and GPR40/FFAR1 in palmitate-induced stimulation of insulin secretion and beta cell death.

Detection of free fatty acid receptor 1 expression: the critical role of negative and positive controls.

Aims/hypothesis: Adequate evaluation of protein expression is a crucial prerequisite for functional studies. Commonly used strategies comprise detection of proteins by specific antibodies using western blotting and immunohistochemical staining, or detection of mRNA by in situ hybridisation and RT-PCR. We evaluated the tools for the detection of free fatty acid receptor 1 (FFAR1) expression.