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Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis

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Investigation of physiological roles of AMPK-activated protein kinase y3

Philipp Jurijvic Rhein

Clinical trials have shown that direct activators of an evolutionary-conserved metabolic sensor, AMP-activated protein kinase (AMPK), are beneficial in preventing/treating a range of metabolic disorders, including type 2 diabetes. These activators, includi ...

EPFL2021

A miR-375/YAP axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells

Iacovos Michael, Mohammad Sadegh Saghafinia

Lung carcinoids are variably aggressive and mechanistically understudied neuroendocrine neoplasms (NENs). Here, we identified and elucidated the function of a miR-375/yes-associated protein (YAP) axis in lung carcinoid (H727) cells. miR-375 and YAP are res ...

NATURE RESEARCH2021

Genetic, metabolic, and molecular insights into the diverse outcomes of diet-induced obesity in mouse

Alexis Maximilien Bachmann

Overweight and obesity are increasingly common public health issues worldwide, leading to a wide range of diseases from metabolic syndrome to steatohepatitis and cardiovascular diseases. While the increase in the prevalence of obesity is partly attributabl ...

EPFL2021

In pancreatic islets from type 2 diabetes patients, the dampened circadian oscillators lead to reduced insulin and glucagon exocytosis

Daniel Sage

Circadian clocks operative in pancreatic islets participate in the regulation of insulin secretion in humans and, if compromised, in the development of type 2 diabetes (T2D) in rodents. Here we demonstrate that human islet alpha- and beta-cells that bear a ...

National Academy of Sciences2020

Augmented mitochondrial energy metabolism is an early response to chronic glucose stress in human pancreatic beta cells

Loïc Dayon, Andreas Wiederkehr, Isabelle Chareyron

Aims/hypothesis In islets from individuals with type 2 diabetes and in islets exposed to chronic elevated glucose, mitochondrial energy metabolism is impaired. Here, we studied early metabolic changes and mitochondrial adaptations in human beta cells durin ...

2020

Targeting Mitochondrial Calcium Uptake with the Natural Flavonol Kaempferol, to Promote Metabolism/Secretion Coupling in Pancreatic beta-cells

Guillaume Jacot

Pancreatic beta-cells secrete insulin to lower blood glucose, following a meal. Maintenance of beta-cell function is essential to preventing type 2 diabetes. In pancreatic beta-cells, mitochondrial matrix calcium is an activating signal for insulin secreti ...

2020

L-Cell Differentiation Is Induced by Bile Acids Through GPBAR1 and Paracrine GLP-1 and Serotonin Signaling

Kristina Schoonjans, Giovanni Sorrentino

Glucagon-like peptide 1 (GLP-1) mimetics are effective drugs for treatment of type 2 diabetes, and there is consequently extensive interest in increasing endogenous GLP-1 secretion and L-cell abundance. Here we identify G-protein-coupled bile acid receptor ...

AMER DIABETES ASSOC2020

Maternal glucose homeostasis is impaired in mouse models of gestational cholestasis

Kristina Schoonjans

Women with intrahepatic cholestasis of pregnancy (ICP), a disorder characterised by raised serum bile acids, are at increased risk of developing gestational diabetes mellitus and have impaired glucose tolerance whilst cholestatic. FXR and TGR5 are modulato ...

Nature Research2020

Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism

Johan Auwerx, Martin Rainer Wohlwend

Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors that are characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with ...

Nature Research2020

Asperuloside Improves Obesity and Type 2 Diabetes through Modulation of Gut Microbiota and Metabolic Signaling

Johan Auwerx, Giorgia Benegiamo

Asperuloside (ASP) is an iridoid glycoside that is extracted from Eucommia leaves. Eucommia is used in traditional Chinese medicine and has a long history of benefits on health and longevity. Here, we investigated the impact of ASP on obesity-related metab ...

2020

90 YEARS OF PROGESTERONE Progesterone receptor signaling in the normal breast and its implications for cancer

Cathrin Brisken, Valentina Scabia

Progesterone is considered as the pregnancy hormone and acts on many different target tissues. Progesterone receptor (PR) signaling is important for normal development and the physiologic function of the breast and impinges on breast carcinogenesis. Both s ...

BIOSCIENTIFICA LTD2020

NAD(+) homeostasis in health and disease

Johan Auwerx, Elena Katsyuba, Mario Romani, Dina Hofer

The conceptual evolution of nicotinamide adenine dinucleotide (NAD(+)) from being seen as a simple metabolic cofactor to a pivotal cosubstrate for proteins regulating metabolism and longevity, including the sirtuin family of protein deacylases, has led to ...

2020

Metabolic and perfusion responses to acute hypoglycemia in the rat cortex: A non-invasive magnetic resonance approach

Rolf Gruetter, Hongxia Lei

Hypoglycemia is critical condition during diabetic treatment that involves intensive insulin therapy, and it may impair brain function. We aimed to compare cortical responses of three hypoglycemic phases and the restoration of glycemia to control levels af ...

Wiley-Blackwell2020