Exendin-4 (Ex4) is a peptide found in the lizard Heloderma suspectum, and it has a high similarity to glucagon-like peptide 1 (GLP-1). It induces insulin secretion without the risk of hypoglycemic episodes. Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase that is predominantly expressed in neurons. Recent studies have shown that this kinase regulates glucose-stimulated insulin secretion. Cdk5 inhibition enhances insulin secretion under conditions of stimulation by high glucose, but not low glucose. In the present study, we examined whether R-roscovitine (R-ros), a Cdk5 inhibitor, enhances insulin secretion induced by Ex4. R-ros induced Ex4-dependent insulin secretion under conditions of high glucose, but not low glucose in MIN6B1 cells. The enhancement by R-ros was also observed in db/db mice, a mouse model of type 2 diabetes. Moreover, long-term treatment with Ex4 and R-ros significantly improved HbA1c compared with treatment using only Ex4. These results suggest that a co-application of R-ros and Ex4 may become a promising therapy for the treatment of type 2 diabetes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2170/physiolsci.RP006607 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Immune checkpoint inhibitor-related diabetes mellitus associated with high signal intensity in diffusion-weighted magnetic resonance imaging of the pancreas at an early clinical stage.
Hormones (Athens)
January 2025
Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but can give rise to immune-related adverse events such as ICI-related diabetes mellitus (DM).
Case Presentation: We herein present the case of a 59-year-old Japanese man with malignant melanoma who developed ICI-related DM after 18 months of nivolumab treatment. He experienced marked hyperglycemia and diabetic ketoacidosis without a personal or family history of diabetes.
Longitudinal association of statin treatment with insulin sensitivity and beta-cell function in the PROMISE cohort.
J Clin Endocrinol Metab
January 2025
Department of Physiology and Pharmacology, Western University, London, Canada.
Context: Statin treatment lowers low-density lipoprotein (LDL) cholesterol thereby reducing cardiovascular risk. Meta-analyses of clinical trials report a higher risk of new-onset type 2 diabetes with statins. Current clinical evidence regarding effects of statins on insulin sensitivity and beta-cell function is limited.
View Article and Find Full Text PDFWoxuanzhongzhou formula improves DHEAS and high-fat diet-induced IR and anovulatory mice via AMPK/PGC1- α/Irisin pathway.
J Ovarian Res
January 2025
Shunyi Hospital, Beijing Traditional Chinese Medicine Hospital, Beijing, 101300, China.
Background: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women of reproductive age. Anovulation is one of the most important clinical features of PCOS, and insulin resistance (IR) is one of the critical pathogenic factors. Woxuanzhongzhou (WXZZ) is a traditional herbal formulation that has shown efficacy in treating PCOS combined with IR, but the underlying mechanism is not clear.
View Article and Find Full Text PDFMetabolic, hormonal profiles and comorbidities in pituitary Cushing's syndrome, adrenal Cushing's syndrome and mild autonomous cortisol secretion: a comparative study.
Postgrad Med
January 2025
Department of Endocrinology, Ankara City Hospital, Ankara, Türkiye.
Purpose: Our study aimed to discern disparities in metabolic, hormonal profiles, and comorbidities among patients with pituitary Cushing (PC), adrenal Cushing (AC), and Mild autonomous cortisol secretion (MACS).
Methods: We conducted a retrospective analysis involving 76 patients diagnosed with PC ( = 26), AC ( = 21), and MACS ( = 29) at our clinic. We compared the groups' demographic data, clinical characteristics, biochemical profiles, hormonal analyses, and surgical interventions.
Dissection of type 2 diabetes: a genetic perspective.
Lancet Diabetes Endocrinol
January 2025
Université de Lille, Inserm UMR1283, CNRS UMR8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille University Hospital, Lille, France; Department of Metabolism, Imperial College London, London, UK. Electronic address:
Diabetes is a leading cause of global mortality and disability, and its economic burden is substantial. This Review focuses on type 2 diabetes, which makes up 90-95% of all diabetes cases. Type 2 diabetes involves a progressive loss of insulin secretion often alongside insulin resistance and metabolic syndrome.
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!