Metabolism, Diabetes, and Cancer

The genetic and dietary landscape of the muscle insulin signalling network

This study uses phosphoproteomics to show how genetic background and diet influence insulin signalling in muscle, revealing key regulators of insulin responsiveness and glycolysis in insulin resistance.

The human AMPKgamma3 R225W mutation does neither enhance basal AMPKgamma3-associated activity nor glycogen in human or mouse skeletal muscle

This study investigates the AMPKgamma3 R225W mutation in human and mouse skeletal muscle, finding no increase in basal activity or glycogen levels, but loss of activation by AICAR/muscle contraction.

Leveraging genetic diversity to identify small molecules that reverse mouse skeletal muscle insulin resistance

The paper identifies small molecules that reverse insulin resistance in mouse skeletal muscle by integrating systems genetics and chemical screening.

Tumor Cytokine-Induced Hepatic Gluconeogenesis Contributes to Cancer Cachexia: Insights from Full Body Single Nuclei Sequencing

The paper shows that tumor-secreted cytokines induce hepatic gluconeogenesis, contributing to hyperglycemia and poor prognosis in cancer cachexia using Drosophila and mouse models.

FBP1 is a nonenzymatic safety valve that curtails AKT activation to prevent insulin hyperresponsiveness

The paper identifies FBP1 as a nonenzymatic regulator that inhibits AKT activation to prevent insulin hyperresponsiveness and associated liver pathologies.

A genetic strategy to measure insulin signaling regulation and physiology in Drosophila

The paper develops a genetic method to measure tissue-specific insulin signaling dynamics in Drosophila using phosphorylated Akt quantification.

Metformin use history and genome-wide DNA methylation profile: potential molecular mechanism for aging and longevity

This study examines the association between metformin use and DNA methylation profiles in blood samples to explore potential epigenetic mechanisms of aging and longevity.

In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states

This study uses multiomic analysis of skeletal muscle in obese and healthy mice to reveal differences in metabolic regulation by metabolites and genes after glucose administration.

Hepatocyte Rap1a Contributes To Obesity- and Statin-Associated Hyperglycemia

This study shows that Rap1a suppresses hepatic glucose production and that its inhibition, via statins, contributes to hyperglycemia in obesity.

Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter

The paper develops a sensitive AMPK activity reporter, ExRai AMPKAR, to study subcellular AMPK dynamics and reveals differential regulation of AMPK activity at lysosomes, mitochondria, and the nucleus.

AMPK is elevated in human cachectic muscle and prevents cancer-induced metabolic dysfunction in mice

This study shows that AMPK is upregulated in human cachectic muscle and that AMPK deficiency in mice worsens cancer-induced metabolic dysfunction and cachexia.

IPMK modulates insulin-mediated suppression of hepatic glucose production

This study shows that IPMK regulates hepatic insulin signaling and gluconeogenesis, with loss of IPMK leading to increased glucose production and insulin resistance in mice.

Prolactin-induced AMPK stabilizes alveologenesis and lactogenesis through regulation of STAT5 signaling

This study shows that prolactin-induced AMPK regulates mammary alveologenesis and lactogenesis by modulating STAT5 signaling in mice.

IL11 stimulates ERK/P90RSK to inhibit LKB1/AMPK and activate mTOR in hepatocytes, the stroma and cancer cells

This study identifies IL11's role in inhibiting LKB1/AMPK and activating mTOR through ERK/P90RSK, leading to metabolic dysfunction and fibrosis in multiple cell types and NASH in mice.

The Mixed Blessing of AMPK Signaling in Cancer Treatments

This study develops a computational model to explore the conflicting roles of AMPK in cancer by simulating metabolic signaling pathways and their effects on tumorigenesis.

Identification of critical genes and biological signaling for metformin treated liver cancer

This study identifies key genes and signaling pathways in metformin-treated liver cancer using RNA sequencing and pathway analysis.

Solute carrier 5A5 regulates systemic glucose homeostasis by mediating glucose absorption in the Drosophila midgut

This study identifies dSLC5A5 as the first Drosophila glucose transporter in the midgut and shows it regulates glucose absorption and systemic homeostasis through endocytosis and lysosomal degradation.

Mct11 deficiency alters hepatic glucose metabolism and energy homeostasis

This study shows that Mct11 deficiency in mice disrupts hepatic glucose and lipid metabolism, mirroring T2D features, and identifies MCT11 as a potential therapeutic target for T2D.

BRAF controls the effects of metformin on neuroblast cell divisions in C. elegans

This study shows metformin suppresses neuronal Q-cell divisions in C. elegans independently of AMPK but through BRAF-MAPK pathway inhibition.

Continuous variable response, kinetic gating and connectivity that govern IS topology are perturbed in hyperinsulinemia

The paper identifies kinetic parameters and connectivity changes in insulin signaling that are disrupted in hyperinsulinemia.

ADP is the dominant controller of AMP-activated protein kinase activity dynamics in skeletal muscle during exercise

The paper develops a mathematical model of AMPK signaling dynamics in skeletal muscle during exercise and finds that ADP, not AMP, is the dominant controller of AMPK activity due to its higher concentration.

Continuous variable response, kinetic gating and connectivity that determine topology of insulin signaling are perturbed in hyper-insulinemic states

The paper identifies kinetic parameters and connectivity changes in insulin signaling that are disrupted in hyper-insulinemic states.

AKT2 deficiency causes sarcopenia and metabolic disorder of skeletal muscle

This study shows that AKT2 deficiency leads to sarcopenia and metabolic disorders in skeletal muscle by affecting glucose uptake, AMPK activity, and mitochondrial biogenesis.

Brain permeable AMPK activator R481 raises glycemia by autonomic nervous system activation and amplifies the counterregulatory response to hypoglycemia in rats

The paper shows that R481, a brain-permeable AMPK activator, raises blood glucose and enhances counterregulatory responses to hypoglycemia in rats without affecting insulin sensitivity.

AMPK promotes induction of a tumor suppressor FLCN through activation of TFEB independently of mTOR

The paper identifies the AMPK-TFEB-FLCN axis as a regulator of cellular and metabolic homeostasis through gene expression and functional studies in mice and zebrafish.

Adenovirus-mediated expression of SIK1 improves hepatic glucose and lipid metabolism in type 2 diabetes mellitus rats

This study shows that overexpressing SIK1 in T2DM rats improves glucose and lipid metabolism by suppressing gluconeogenesis and lipogenesis through specific signaling pathways.

A Yeast Global Genetic Screen Reveals that Metformin Induces an Iron Deficiency-Like State

The paper uses hdPCA to identify gene functions and pathways affected by metformin, revealing an iron deficiency-like cellular response.