The importance of pancreatic versus intestinal-derived GLP-1 for glucose homeostasis is controversial. We detected active GLP-1 in the mouse and human pancreas, albeit at extremely low levels relative to glucagon. Accordingly, to elucidate the metabolic importance of intestinal proglucagon-derived peptides (PGDPs), we generated mice with reduction of Gcg expression within the distal (Gcg) or entire (Gcg) gut. Substantial reduction of gut Gcg expression markedly reduced circulating levels of GLP-1, and impaired glucose homeostasis, associated with increased levels of GIP, and accelerated gastric emptying. Gcg mice similarly exhibited lower circulating GLP-1 and impaired oral glucose tolerance. Nevertheless, plasma levels of insulin remained normal following glucose administration in the absence of gut-derived GLP-1. Collectively, our findings identify the essential importance of gut-derived PGDPs for maintaining levels of circulating GLP-1, control of gastric emptying, and glucose homeostasis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140521 | PMC |
| http://dx.doi.org/10.1016/j.cmet.2019.08.009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
sVEGFR3 alleviates myocardial ischemia/reperfusion injury through regulating mitochondrial homeostasis and immune cell infiltration.
Apoptosis
January 2025
Department of Cardiac Surgery, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan II Rd, Guangzhou, 510080, China.
Recent studies have suggested that sVEGFR3 is involved in cardiac diseases by regulating lymphangiogenesis; however, results are inconsistent. The aim of this study was to investigate the function and mechanism of sVEGFR3 in myocardial ischemia/reperfusion injury (MI/RI). sVEGFR3 effects were evaluated in vivo in mice subjected to MI/RI, and in vitro using HL-1 cells exposed to oxygen-glucose deprivation/reperfusion.
View Article and Find Full Text PDFPotential Effect of Cinnamaldehyde on Insulin Resistance Is Mediated by Glucose and Lipid Homeostasis.
Nutrients
January 2025
Instituto de Bioeletricidade Celular (IBIOCEL): Ciência & Saúde, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Rua João Pio Duarte Silva, 241, Sala G 301, Florianópolis 88038-000, SC, Brazil.
Diabetes mellitus is a metabolic syndrome that has grown globally to become a significant public health challenge. Hypothesizing that the plasma membrane protein, transient receptor potential ankyrin-1, is a pivotal target in insulin resistance, we investigated the mechanism of action of cinnamaldehyde (CIN), an electrophilic TRPA1 agonist, in skeletal muscle, a primary insulin target. Specifically, we evaluated the effect of CIN on insulin resistance, hepatic glycogen accumulation and muscle and adipose tissue glucose uptake.
View Article and Find Full Text PDFThe Effect of the 14:10-Hour Time-Restricted Feeding (TRF) Regimen on Selected Markers of Glucose Homeostasis in Diet-Induced Prediabetic Male Sprague Dawley Rats.
Nutrients
January 2025
Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa.
Background: Prediabetes is a condition that often precedes the onset of type 2 diabetes mellitus (T2DM). Literature evidence indicates that prediabetes is reversible, making it an important therapeutic target for preventing the progression to T2DM. Several studies have investigated intermittent fasting as a possible method to manage or treat prediabetes.
View Article and Find Full Text PDFThe Gut Microbiota-Related Antihyperglycemic Effect of Metformin.
Pharmaceuticals (Basel)
January 2025
Department of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, Poland.
It is critical to sustain the diversity of the microbiota to maintain host homeostasis and health. Growing evidence indicates that changes in gut microbial biodiversity may be associated with the development of several pathologies, including type 2 diabetes mellitus (T2DM). Metformin is still the first-line drug for treatment of T2DM unless there are contra-indications.
View Article and Find Full Text PDFType 2 Diabetes Induces Mitochondrial Dysfunction in Zebrafish Skeletal Muscle Leading to Diabetic Myopathy via the miR-139-5p/NAMPT Pathway.
Int J Mol Sci
January 2025
State Key Laboratory of Developmental Biology of Freshwater Fish, Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, China.
Type 2 diabetes mellitus (T2DM) is a common metabolic disease that is frequently accompanied by multiple complications, including diabetic myopathy, a muscle disorder that is mainly manifested as decreased muscle function and reduced muscle mass. Diabetic myopathy is a relatively common complication among patients with diabetes that is mainly attributed to mitochondrial dysfunction. Therefore, we investigated the mechanisms underlying diabetic myopathy development, focusing on the role of microRNAs (miRs).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!