DECORIN, a triceps-derived myokine, protects sorted β-cells and human islets against chronic inflammation associated with type 2 diabetes.

Aim: Pancreatic β-cells are susceptible to inflammation, leading to decreased insulin production/secretion and cell death. Previously, we have identified a novel triceps-derived myokine, DECORIN, which plays a pivotal role in skeletal muscle-to-pancreas interorgan communication. However, whether DECORIN can directly impact β-cell function and susceptibility to inflammation remains unexplored.

Integrin and autocrine IGF2 pathways control fasting insulin secretion in β-cells.

Elevated levels of fasting insulin release and insufficient glucose-stimulated insulin secretion (GSIS) are hallmarks of diabetes. Studies have established cross-talk between integrin signaling and insulin activity, but more details of how integrin-dependent signaling impacts the pathophysiology of diabetes are needed. Here, we dissected integrin-dependent signaling pathways involved in the regulation of insulin secretion in β-cells and studied their link to the still debated autocrine regulation of insulin secretion by insulin/insulin-like growth factor (IGF) 2-AKT signaling.

Beta-Cell-Specific Expression of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 5 Aggravates High-Fat Diet-Induced Impairment of Islet Insulin Secretion in Mice.

Nicotinamide adenine dinucleotide phosphate oxidases (NOX-es) produce reactive oxygen species and modulate β-cell insulin secretion. Islets of type 2 diabetic subjects present elevated expression of NOX5. Here, we sought to characterize regulation of NOX5 expression in human islets and to uncover the relevance of NOX5 in islet function using a novel mouse model expressing NOX5 in doxycycline-inducible, β-cell-specific manner (RIP/rtTA/NOX5 mice).

Role and impact of the extracellular matrix on integrin-mediated pancreatic β-cell functions.

Understanding the organisation and role of the extracellular matrix (ECM) in islets of Langerhans is critical for maintaining pancreatic β-cells, and to recognise and revert the physiopathology of diabetes. Indeed, integrin-mediated adhesion signalling in response to the pancreatic ECM plays crucial roles in β-cell survival and insulin secretion, two major functions, which are affected in diabetes. Here, we would like to present an update on the major components of the pancreatic ECM, their role during integrin-mediated cell-matrix adhesions and how they are affected during diabetes.

IL-13 improves beta-cell survival and protects against IL-1beta-induced beta-cell death.

Objectives: IL-13 is a cytokine classically produced by anti-inflammatory T-helper-2 lymphocytes; it is decreased in the circulation of type 2 diabetic patients and impacts positively on liver and skeletal muscle. Although IL-13 can exert positive effects on beta-cell lines, its impact and mode of action on primary beta-cell function and survival remain largely unexplored.

Methods: Beta-cells were cultured for 48 h in the presence of IL-13 alone or in combination with IL-1β or cytokine cocktail (IL-1β, IFNγ, TNFα).