Metabolism, Diabetes, and Cancer

Beyond presence and absence: a survey of TOR and AMPK across 210 eukaryotes reveals unusually long coccidian AMPKγ

The paper surveys TOR and AMPK across 210 eukaryotes, revealing lineage-specific variations in component repertoires, sequence features, and component associations.

MCT6 is an intestinal Lac-Phe exporter required for metformin-associated weight loss

This study identifies MCT6 as an intestinal exporter of Lac-Phe, showing its role in metformin-induced weight loss and systemic metabolite regulation.

Manganese availability determines insulin sensitivity by enhancing Akt activity

This study identifies manganese as a regulator of Akt activity independent of PI3K, showing it enhances Akt catalytic efficiency and interacts with insulin to modulate glucose homeostasis.

Personalized phosphoproteomics establish mTORC1 as a regulator of exercise-induced insulin sensitization in human skeletal muscle

The paper uses personalized phosphoproteomics to show that mTORC1 regulates exercise-induced insulin sensitization in human skeletal muscle through a feedback pathway involving MKNK2 and eIF4G1.

Fine tuning energy metabolism in skeletal muscle: Discovery of a novel autoinhibitory mechanism in the N-terminal extension of AMPKγ3

This study identifies an autoinhibitory mechanism in the N-terminal extension of AMPKγ3 that regulates basal activity in skeletal muscle, offering a target for T2DM therapies.

Drosophila Nepl15 controls glycogen and lipid storage by modulating insulin signaling

This study shows that Nepl15 regulates glycogen and lipid storage in Drosophila by modulating insulin signaling, affecting metabolic homeostasis without altering food intake.

Exercise training improves exercise capacity independent of AMPKa2 T172-mediated adaptations in skeletal muscle

This study shows that AMPK2 T172 activation is necessary for mitochondrial and angiogenic adaptations in skeletal muscle from exercise training, but not for improved exercise capacity.

Membrane progesterone receptor signaling reverses hyperglycemia and insulin resistance in obese mice

This study shows that activating membrane progesterone receptors improves glucose homeostasis and insulin sensitivity in obese mice through AMPK-dependent metabolic reprogramming.

Insulin-independent glucose uptake in skeletal muscle by coupled SGLT and Na,K-ATPase transport

The paper identifies a novel insulin-independent glucose uptake pathway in skeletal muscle, termed mSGLT, which operates via SGLT and Na,K-ATPase and is active during exercise and adrenergic stimulation.

A full-length single nuclei transcriptomic atlas of human skeletal muscle insulin resistance

The paper generates a nucleus-resolved transcriptomic atlas of skeletal muscle insulin resistance using single-nucleus transcriptomics and stable isotope-labeled clamps, identifying cell-specific molecular programs and targets.

Anti-diabetic drug Repaglinide induces Apoptosis, Cell Cycle Arrest, and Inhibits Cell Migration in Human Breast and Lung Cancer Cells.

This study investigates repaglinide's anticancer effects on breast and lung cancer cells, showing cytotoxicity, apoptosis, cell cycle arrest, and reduced migration.

Ampk alpha2 T172 Activation Dictates Exercise Performance and Energy Transduction in Skeletal Muscle

This study shows that activating AMPK alpha2 T172 in skeletal muscle improves exercise performance and energy transduction, and its disruption mimics type 2 diabetes features.

F26BP enables control of glycolysis rate independent of energy state

The paper shows F26BP regulates glycolytic rate independently of energy state, distinguishing it from other regulators, and identifies downstream intermediates that control F26BP levels.

Alpha Parvin Promotes Glucose Uptake and Metabolism in Skeletal Muscle with Minimal Influence on Hepatic Insulin Sensitivity

This study shows that Parvin in skeletal muscle is essential for insulin-stimulated glucose uptake and mitochondrial function, while having little effect on liver insulin sensitivity.

4-Hexylresorcinol Enhances Skeletal Muscle Glucose Handling through the AMPK-GLUT4 axis in Diabetic Rats

This study shows that 4-hexylresorcinol improves glucose metabolism in diabetic rats by enhancing AMPK-GLUT4 signaling and glycogen content.

TAS1R3 regulates GTPase signaling in human skeletal muscle cells for glucose uptake.

This study shows TAS1R3 regulates glucose uptake in skeletal muscle via a Rac1 and phospho-cofilin pathway, independent of IRS1-AKT and Galphaq/11, and identifies it as a potential therapeutic target for T2D.

mRNA and Protein Expression of Fetal Insulin Receptor in Breast Cancer Cell Lines

The paper examines mRNA and protein expression of insulin receptor isoforms in breast cancer cell lines and finds that IR-A is overexpressed compared to IR-B, with IR-A protein expression demonstrated for the first time.

Cyclin Y Overexpression Drives a Fatal Metabolic Syndrome via Defective Glucose Homeostasis

This study shows that CCNY overexpression causes a fatal metabolic syndrome by disrupting glucose homeostasis and inducing a Warburg-like metabolic shift.

The fate of pyruvate dictates cell growth by modulating cellular redox potential

The paper shows that pyruvate metabolism affects cell growth in post-mitotic cells by altering redox balance and metabolic pathways, despite active growth signals.

AMPKα2 isoform mediates mTORC2 activation by glucose starvation in endothelial cells

The paper investigates how AMPKα2 isoform activates mTORC2 during glucose starvation in endothelial cells and finds it is functionally uncoupled from glucose uptake adaptation.

AKT signaling in hepatocytes rapidly increases glucose phosphorylation and contribution to glycogen without affecting metabolite pool sizes or glycogen breakdown

Common and distinct roles of AMPKγ isoforms in small-molecule activator-stimulated glucose uptake in mouse skeletal muscle

This study identifies distinct roles of AMPKγ isoforms in glucose uptake in skeletal muscle, showing γ1 is required for ADaM site activator-stimulated uptake but not AMP-binding activators.

AMPK acts to remove immune barriers to CD8+ T cell-mediated immunity against hepatocellular carcinoma

This study shows that aldometanib activates AMPK to enhance CD8+ T cell infiltration and control hepatocellular carcinoma growth in immune-competent mice.

Reductive death is averted by an ancient metabolic switch.

The paper identifies reductive stress as a toxicity of biguanides like metformin, showing that fatty acid biosynthesis protects against this effect and could be targeted in cancer.

LKB1 Spatially Regulates AMPK Activity Coordinate Cellular Oxidative Stress Response

This study shows that LKB1 spatially regulates AMPK activity in response to oxidative stress, affecting metabolic and gene expression changes, and identifies impaired LKB1-AMPK signaling in certain cancers.

SAMP1 Facilitates Importin-Mediated Nuclear Translocation to Activate the PKA/CREB Pathway and Hepatic Gluconeogenesis

This study identifies SAMP1 as a regulator of hepatic gluconeogenesis by enhancing Importin-mediated nuclear translocation of PKA, thereby activating the PKA/CREB pathway.

Acute AMPK activation does not adequately stimulate insulin signaling in skeletal muscle models of Myotonic Dystrophy Type 1

This study shows that acute AMPK activation fails to improve insulin signaling in DM1 mouse and human models, indicating impaired insulin resistance mechanisms.

Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycemic control

This study shows metformin lowers blood glucose by inhibiting intestinal mitochondrial complex I, increasing lactate and GDF15, and promoting glucose uptake.

Mechanism and cellular actions of the potent AMPK inhibitor BAY-3827

This paper describes the mechanism and cellular effects of the potent AMPK inhibitor BAY-3827, showing it selectively blocks AMPK-dependent functions.

Fasting-induced hepatic gluconeogenesis is compromised in Anxa6-/- mice

This study shows that Anxa6-/- mice have impaired fasting-induced hepatic gluconeogenesis, leading to hypoglycaemia and reliance on lipid oxidation.