Glucagon, a 29-amino acid polypeptide hormone, is an essential therapeutic agent used in the emergency treatment of hypoglycemia. However, glucagon is inherently unstable in aqueous solution. While glucagon equilibrates between unordered and the secondary α-helix state in solution, it can quickly transform into a different secondary β-sheet-rich amyloid-like fibril/oligomer structure under various conditions. Since changes in the secondary structure of glucagon can cause significant impacts, structure analysis is necessary and essential to assess the safety of the product. This study analyzed the secondary structure of glucagon products at the release and at the expiry using circular dichroism spectroscopy (CD) and 2D Nuclear Overhauser effect spectroscopy (2D NOESY). In order to also determine if structural differences exist between glucagon produced through different manufacturing processes, synthetic and recombinant glucagon products were used and compared. The CD results indicated that for all release and expired glucagon products, the structure compositions were 14 to 16% α-helix, 17 to 19% β-strand, 14 to 15% Turn, and 53 to 54% Unordered. This was consistent with the 2D NOESY analysis which showed that both products had an approximate α-helix composition of 14 to 17%. Overall, there were no significant differences in terms of the secondary structure between synthetic and recombinant glucagon products both at the release and at the expiry.
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http://dx.doi.org/10.3390/molecules27227805 | DOI Listing |
J Endocrinol
January 2025
N Inagaki, Department of Diabetes, Endocrinology and Nutrition, Kyoto University, Kyoto, Japan.
Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RAs) are widely used as antidiabetic and anti-obesity agents. Although conventional GLP-1 RAs such as liraglutide and semaglutide are acylated with fatty acids to delay their degradation by dipeptidylpeptidase-4 (DPP-4), the manufacturing process is challenging. We previously developed selectively lipidated GLP-1 peptides at their only tryptophan residue (peptide A having one 8-amino-3,6-dioxaoctanoic acid (miniPEG) linker and peptide B having three miniPEG linkers).
View Article and Find Full Text PDFCell 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 PDFAm J Ther
January 2025
Basic, Preventive and Clinical Sciences Department, Transilvania University, Brasov, Romania.
Background: Medications initially intended for diabetes treatment are now being used by other patients for weight loss. In the specialized literature, there are numerous meta-analyses investigating this aspect.
Areas Of Uncertainty: The authors aimed to explore whether the application of scientometric methods for literature review within meta-analyses could provide clear answers to specific research questions.
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.
J Pharm Policy Pract
December 2024
Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Background: High prices and other access barriers have contributed to the rise of a market for compounded glucagon-like peptide-1 receptor agonists for weight loss in the United States. This market has not been systematically studied. We conducted a pilot study to assess the prevalence, characteristics, and advertising content of direct-to-consumer providers of compounded glucagon-like peptide-1 products for weight loss in Colorado.
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