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Single and Combined Impact of Semaglutide, Tirzepatide, and Metformin on β-Cell Maintenance and Function Under High-Glucose-High-Lipid Conditions: A Comparative Study.
Int J Mol Sci
January 2025
Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada.
Type 2 diabetes (T2D), the most common form, is marked by insulin resistance and β-cell failure. β-cell dysfunction under high-glucose-high-lipid (HG-HL) conditions is a key contributor to the progression of T2D. This study evaluates the comparative effects of 10 nM semaglutide, 10 nM tirzepatide, and 1 mM metformin, both alone and in combination, on INS-1 β-cell maintenance and function under HG-HL conditions.
View Article and Find Full Text PDFNon-canonical hepatic androgen receptor mediates glucagon sensitivity in female mice through the PGC1α/ERRα/mitochondria axis.
Cell Rep
January 2025
Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China; Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China. Electronic address:
Glucagon has recently been found to modulate liver fat content, in addition to its role in regulating gluconeogenesis. However, the precise mechanisms by which glucagon signaling synchronizes glucose and lipid metabolism in the liver remain poorly understood. By employing chemical and genetic approaches, we demonstrate that inhibiting the androgen receptor (AR) impairs the ability of glucagon to stimulate gluconeogenesis and lipid catabolism in primary hepatocytes and female mice.
View Article and Find Full Text PDFDose-related effects of calcium to enhance the effects of L-tryptophan on gut hormones and energy intake in obesity.
J Clin Endocrinol Metab
January 2025
Adelaide Medical School, University of Adelaide, Adelaide, Australia.
Context: In males of normal weight, intraduodenal administration of calcium enhances the effects of the amino acid, L-tryptophan (Trp), to suppress energy intake, associated with greater stimulation of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY) secretion (key mechanisms underlying the regulation of pyloric motility and gastric emptying), but not gastrin or glucose-dependent insulinotropic polypeptide (GIP).
Objective: Given the implications for the management of obesity, the current study evaluated the effects of calcium, when administered alone and in combination with Trp, on gut hormone secretion, antropyloroduodenal motility and energy intake in males with obesity.
Methods: Fifteen males with obesity and without type 2 diabetes (mean±SD; age: 27±8 years; body mass index: 30±2 kg/m2; HbA1c: 5.
Gestational diabetes mellitus-derived miR-7-19488 targets PIK3R2 mRNA to stimulate the abnormal development and maturation of offspring-islets.
Life Sci
January 2025
Department of Pharmacology, School of Pharmacy, Qingdao University, No. 308 Ningxia Road, Shinan District, Qingdao 266021, China; Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250014, China. Electronic address:
Aims: Gestational diabetes mellitus (GDM) provides offspring with a hyper-metabolic intrauterine microenvironment. In this study, we aimed to identify key differential microRNAs in GDM-derived exosomes and explore the potential mechanisms of abnormal embryonic development of islets in offspring.
Main Methods: Exosomes were extracted from umbilical vein blood of GDM and non-GDM (NGDM) parturients for microRNA sequencing.
Association of dipeptidyl peptidase-4 with Alzheimer's disease: A new therapeutic prospect.
J Alzheimers Dis
January 2025
Department of Physiology and Pathophysiology, Jiaxing University Medical College, Jiaxing, China.
Alzheimer's disease (AD) is the most common disease associated with cognitive dysfunction, which is closely associated with type 2 diabetes mellitus (T2DM) in clinical manifestations, pathological changes and prevention. Inhibition of dipeptidyl peptidase 4 (DPP-4) can lower blood glucose levels by stimulating insulin secretion. Besides, it can affect cognitive function through the neuroprotective effect of DPP-4 substrates, such as glucose-dependent insulin peptide and glucagon-like peptide-1, the proteolytic effect on amyloid-β and the protective effect on neuronal structure.
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