Prolyl-4-hydroxylase 3 maintains β cell glucose metabolism during fatty acid excess in mice.

The α-ketoglutarate-dependent dioxygenase, prolyl-4-hydroxylase 3 (PHD3), is an HIF target that uses molecular oxygen to hydroxylate peptidyl prolyl residues. Although PHD3 has been reported to influence cancer cell metabolism and liver insulin sensitivity, relatively little is known about the effects of this highly conserved enzyme in insulin-secreting β cells in vivo. Here, we show that the deletion of PHD3 specifically in β cells (βPHD3KO) was associated with impaired glucose homeostasis in mice fed a high-fat diet.

Beta-aminoisobutyric acid is released by contracting human skeletal muscle and lowers insulin release from INS-1 832/3 cells by mediating mitochondrial energy metabolism.

Aims/hypothesis: This study aimed to examine if beta-aminoisobutyric acid (BAIBA) is (i) secreted by skeletal muscle in humans during exercise, (ii) associated with insulin secretory function in vivo, and (iii) directly linked with acute glucose-mediated insulin release by pancreatic beta cells .

Methods: Following 2-weeks of single-leg immobilization, plasma BAIBA concentrations were measured in the brachial artery and the femoral veins of each leg in healthy male subjects, at rest and during two-legged dynamic knee-extensor exercise. During a 2-h hyperglycamic clamp, insulin secretory function and levels of plasma BAIBA were assessed in non-diabetic individuals, non-diabetic individuals following 24-h hyperglycemia and patients with type 2 diabetes.

AMPK activation induces mitophagy and promotes mitochondrial fission while activating TBK1 in a PINK1-Parkin independent manner.

Mitophagy is a key process regulating mitochondrial quality control. Several mechanisms have been proposed to regulate mitophagy, but these have mostly been studied using stably expressed non-native proteins in immortalized cell lines. In skeletal muscle, mitophagy and its molecular mechanisms require more thorough investigation.

The benefits of physical exercise for the health of the pancreatic β-cell: a review of the evidence.

New Findings: What is the topic of this review? This review discusses the evidence of the benefits of exercise training for β-cell health through improvements in function, proliferation and survival which may have implications in the treatment of diabetes. What advances does it highlight? This review highlights how exercise may modulate β-cell health in the context of diabetes and highlights the need for further exploration of whether β-cell preserving effects of exercise translates to T1D.

Abstract: Physical exercise is a core therapy for type 1 and type 2 diabetes.

Do skeletal muscle-secreted factors influence the function of pancreatic β-cells?

Skeletal muscle is an endocrine organ that secretes a variety of compounds including proteins (myokines), metabolites, microRNAs (miRNAs), and exosomes, many of which are regulated by exercise and play important roles in endocrine signaling. Interorgan communication via muscle-secreted factors therefore provides a novel area for investigation and implicates the importance of skeletal muscle in the pathophysiology of metabolic diseases such as type 2 diabetes (T2D). Given that underlying molecular mechanisms of T2D are subject of ongoing research, in light of new evidence it is probable that interorgan cross-talk between skeletal muscle and pancreatic β-cells plays an important part.