The mitochondrial mRNA-stabilizing protein SLIRP regulates skeletal muscle mitochondrial structure and respiration by exercise-recoverable mechanisms.

Decline in mitochondrial function is linked to decreased muscle mass and strength in conditions like sarcopenia and type 2 diabetes. Despite therapeutic opportunities, there is limited and equivocal data regarding molecular cues controlling muscle mitochondrial plasticity. Here we uncovered that the mitochondrial mRNA-stabilizing protein SLIRP, in complex with LRPPRC, is a PGC-1α target that regulates mitochondrial structure, respiration, and mtDNA-encoded-mRNA pools in skeletal muscle.

The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator.

Background: Metabolic effects of empagliflozin treatment include lowered glucose and insulin concentrations, elevated free fatty acids and ketone bodies and have been suggested to contribute to the cardiovascular benefits of empagliflozin treatment, possibly through an improved cardiac function. We aimed to evaluate the influence of these metabolic changes on cardiac function in patients with T2D.

Methods: In a randomized cross-over design, the SGLT2 inhibitor empagliflozin (E) was compared with insulin (I) treatment titrated to the same level of glycemic control in 17 patients with type 2 diabetes, BMI of > 28 kg/m, C-peptide > 500 pM.

Investigating the roles of hyperglycaemia, hyperinsulinaemia and elevated free fatty acids in cardiac function in patients with type 2 diabetes via treatment with insulin compared with empagliflozin: protocol for the HyperCarD2 randomised, crossover trial.

Introduction: Type 2 diabetes (T2D) is characterised by elevated plasma glucose, free fatty acid (FFA) and insulin concentrations, and this metabolic profile is linked to diabetic cardiomyopathy, a diastolic dysfunction at first and increased cardiovascular disease (CVD) risk. Shifting cardiac metabolism towards glucose utilisation has been suggested to improve cardiovascular function and CVD risk, but insulin treatment increases overall glucose oxidation and lowers lipid oxidation, without reducing CVD risk, whereas SGLT2 inhibitors (SGLT2i) increase FFA, ketone body concentrations and lipid oxidation, while decreasing insulin concentrations and CVD risk. The aim of the present study is to elucidate the importance of different metabolic profiles obtained during treatment with a SGLT2i versus insulin for myocardial function in patients with T2D.

Effects of Roux-en-Y gastric bypass on circulating follistatin, activin A, and peripheral ActRIIB signaling in humans with obesity and type 2 diabetes.

Background: Roux-en-Y gastric bypass (RYGB) surgery is a therapeutic intervention for morbid obesity and type 2 diabetes (T2D) that improves metabolic regulation. Follistatin (Fst) could be implicated in improved glycemia as it is highly regulated by RYGB. However, it is unknown if metabolic status, such as T2D, alters the Fst response to RYGB.

Mechanisms involved in follistatin-induced hypertrophy and increased insulin action in skeletal muscle.

Background: Skeletal muscle wasting is often associated with insulin resistance. A major regulator of muscle mass is the transforming growth factor β (TGF-β) superfamily, including activin A, which causes atrophy. TGF-β superfamily ligands also negatively regulate insulin-sensitive proteins, but whether this pathway contributes to insulin action remains to be determined.