Review
Biochemistry & Molecular Biology
Safia Costes, Gyslaine Bertrand, Magalie A. Ravier
Summary: Type 2 diabetes is characterized by chronic hyperglycemia due to functional beta-cell decline and reduced insulin sensitivity. The decrease in beta-cell mass in T2D is partly attributed to beta-cell apoptosis triggered by diabetogenic situations. This review discusses the molecular mechanisms involved in pancreatic beta-cell apoptosis in such situations and potential protective pathways by glucagon-like peptide-1-based therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Antonia Diaz-Ganete, Aranzazu Quiroga-de-Castro, Rosa M. Mateos, Francisco Medina, Carmen Segundo, Alfonso M. Lechuga-Sancho
Summary: This study aims to characterize the survival and function of 1.1E7 cells under toxic conditions and found that different stimuli induce apoptosis and ER stress, decrease mRNA levels of insulin secretory pathway genes, and abolish insulin release capability in response to glucose.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Baiyi Yan, Yanchun Gong, Wei Meng, Huizhen Sun, Wenxi Li, Kaizhi Ding, Caixia Dang, Xiaofei Gao, Wei Sun, Chunhua Yuan, Songhua Wang, Li-Hua Yao
Summary: This study found that cordycepin, an extract from Cordyceps militaris, has a significant protective effect on glucotoxicity and lipotoxicity-induced damage in pancreatic islet cells. It improves cell viability, energy metabolism, and insulin synthesis and secretion. The mechanism may involve reducing ROS levels, increasing ATP content, causing membrane depolarization, balancing Ca2+ concentration, and inhibiting cell apoptosis through downregulation of the JNK pathway.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Gastroenterology & Hepatology
Raja Gopal Reddy Mooli, Dhanunjay Mukhi, Anil K. Pasupulati, Simon S. Evers, Ian J. Sipula, Michael Jurczak, Randy J. Seeley, Yatrik M. Shah, Sadeesh K. Ramakrishnan
Summary: The study identifies the crucial role of intestinal HIF signaling, particularly HIF-2α, in regulating the lipid sensor GPR40 for lipid-mediated GLP-1 secretion, suggesting HIF-2α as a potential target to induce endogenous GLP-1 secretion.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jiao Wang, Li-Rui Wei, Yan-Ling Liu, Cheng-Zhi Ding, Feng Guo, Qian Qin, Feng-Jiao Huang, Ying Xin, Sheng-Nan Ma, Qiu-Ran Zhai, Shou-Jun Wang, Gui-Jun Qin
Summary: The study found that berberine promotes GLP-1 production by intestinal L cells through various mechanisms, such as down-regulating miR-106b expression, increasing the expressions of beta-catenin and TCF4, reducing triglycerides and cholesterol levels in serum, and activating GLP-1 production through the beta-catenin/TCF4 signaling pathway in intestinal L cells.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Christopher E. Shannon, Aurora Merovci, Marcel Fourcaudot, Devjit Tripathy, Muhammad Abdul-Ghani, Hu Wang, Xianlin Han, Luke Norton, Ralph A. DeFronzo
Summary: This study demonstrates that the major lipid pools in skeletal muscle are not affected by increased glucose availability, suggesting that glucotoxicity and lipotoxicity promote insulin resistance through distinct mechanistic pathways.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Pharmacology & Pharmacy
Wenbin Wu, Qingsong Xia, Yujin Guo, Hongzhan Wang, Hui Dong, Fuer Lu, Fen Yuan
Summary: This study confirmed that berberine can promote the secretion of GLP-1 in intestinal L cells and islet alpha cells through activation of the GLP-1/GLP-1R/PKA signaling pathway, thus improving the function of islet beta cells and treating T2DM.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Endocrinology & Metabolism
Amaara Marzook, Alejandra Tomas, Ben Jones
Summary: GLP-1R is a GPCR that mediates the effects of GLP-1, important in the treatment of T2D. Biased GLP-1R agonists have been discovered, showing altered trafficking profiles and selective engagement with different intracellular effectors for studying the mechanisms and physiological importance of these processes.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Immunology
Jing Qi, Xueqing Yan, Lanqian Li, Kexin Qiu, Weizhi Huang, Zixiong Zhou
Summary: Immune-inflammatory responses play a key role in the development of nonalcoholic steatohepatitis (NASH). A recent study showed that CXC motif chemokine ligand 5 (CXCL5) is highly expressed in a NASH mouse model and its neutralization can alleviate the severity of NASH by reducing lipid accumulation, cell death, and fibrosis in injured livers. In vitro experiments revealed that CXCL5 exacerbates hepatotoxicity and lipid deposition in hepatocytes co-cultured with Kupffer cells (KCs), rather than in single-cultured hepatocytes. Mechanistically, CXCL5 promotes lipotoxicity of hepatocytes by upregulating NLRP3/Caspase-1/IL-1β signaling in KCs. These findings highlight the importance of CXCL5 in the pathogenesis of NASH.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Physiology
Jun Ren, Ne N. Wu, Shuyi Wang, James R. Sowers, Yingmei Zhang
Summary: The rise in heart failure prevalence is partly due to increasing rates of overweight and obesity. Evidence supports the existence of obesity cardiomyopathy as a unique disease entity that develops independently of other heart diseases. Clinical and experimental research have identified pathological changes in myocardial structure and function in obesity, highlighting various cellular and molecular mechanisms underlying this condition.
PHYSIOLOGICAL REVIEWS
(2021)
Article
Agriculture, Multidisciplinary
Weiping Su, Yanan Li, Alan Kueichieh Chang, Tongling Sheng, Ying Pei, Jianxin Li, Haoran Li, Kai Liu, Liuping Xu, Wenbao Liu, Jiao Ai, Zhicheng Zhang, Yimeng Wang, Zhen Jiang, Xiao Liang
Summary: Six new alkaloids were isolated from Portulaca oleracea, with one of them (compound 3) found to have the ability to stimulate the release of GLP-1, potentially reducing blood glucose levels. In addition, compound 3 also showed slightly faster absorption than nateglinide in pharmacokinetic analysis.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Yibo Zong, Wenjing Chen, Yongsen Zhao, Xiaoyi Suo, Xiaojing Yang
Summary: In this study, a model of Salmonella-infected piglets was established to investigate the effects of Salmonella infection on enteroendocrine L cell function. The results showed that Salmonella infection can reduce GLP-1 secretion by inducing pyroptosis of intestinal L cells, which may eventually result in hyperglycemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Justyna Janikiewicz, Aneta M. Dobosz, Katarzyna Majzner, Tytus Bernas, Agnieszka Dobrzyn
Summary: The accumulation of surplus lipids in the pancreas triggers changes in the structure and function of type 2 diabetes-affected islets. Pancreatic beta-cells have limited capacity to store fat in lipid droplets (LDs). Stearoyl-CoA desaturase 1 (SCD1) plays a critical role in LD metabolism and affects beta-cell survival. Deficiency in SCD1 activity leads to changes in LD composition and metabolism, which can impact the susceptibility of pancreatic beta-cells to palmitate.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Biology
Sayantani Pramanik Palit, Roma Patel, Nishant Parmar, Nirali Rathwa, Nilay Dalvi, A. V. Ramachandran, Rasheedunnisa Begum
Summary: The combination therapy of pitavastatin and L-glutamine can ameliorate type 2 diabetes (T2D) by inducing beta-cell regeneration and regulating glucose homeostasis.
Article
Biochemistry & Molecular Biology
Yadi Tang, Thomas Ploetz, Markus H. Graeler, Ewa Gurgul-Convey
Summary: This study reveals that the regulation of SPL may be crucially involved in the susceptibility of pancreatic beta-cells to lipotoxicity, as SPL plays an important role in modulating the damage process of pancreatic beta-cells induced by FFAs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Nupur M. Pathak, Paul J. B. Millar, Varun Pathak, Peter R. Flatt, Victor A. Gault
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2018)
Article
Biochemistry & Molecular Biology
J. Michael Conlon, Milena Mechkarska, Yasser H. Abdel-Wahab, Peter R. Flatt
Review
Biochemistry & Molecular Biology
R. Charlotte Moffett, Violetta Naughton
Article
Pharmacology & Pharmacy
Dipak Sarnobat, Charlotte R. Moffett, Neil Tanday, Frank Reimann, Fiona M. Gribble, Peter R. Flatt, Andrei I. Tarasov
BIOCHEMICAL PHARMACOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Galyna Graham, J. Michael Conlon, R. Charlotte Moffett, Yasser H. Abdel-Wahab, Peter R. Flatt
Summary: The study showed that long-acting, dual-agonist anti-diabetic peptides can induce alpha-cell to beta-cell transdifferentiation, leading to increased pancreatic insulin content and plasma insulin concentrations. This suggests therapeutic potential for using proglucagon-derived peptides from phylogenetical ancient fish in diabetes treatment.
JOURNAL OF PEPTIDE SCIENCE
(2021)
Article
Endocrinology & Metabolism
D. Sarnobat, R. C. Moffett, P. R. Flatt, A. I. Tarasov
Summary: The study showed that metformin and rosiglitazone can help slow down the reduction of beta-cell pool in streptozotocin-induced diabetes, while tolbutamide may exacerbate beta-cell apoptosis but potentially protect beta-cells from chronic hyperglycemia by increasing insulin secretion directly.
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
(2022)
Article
Plant Sciences
Prawej Ansari, Peter R. Flatt, Patrick Harriott, J. M. A. Hannan, Yasser H. A. Abdel-Wahab
Summary: The study demonstrated the antidiabetic effects of Acacia arabica bark extract, showing potential as a treatment for diabetes. The isolated phytoconstituents, including quercetin and kaempferol, improved glucose tolerance and insulin secretion, indicating the benefits of using them as antidiabetic agents.
Article
Multidisciplinary Sciences
Ananyaa Sridhar, Dawood Khan, Mahmoud Abdelaal, Jessie A. Elliott, Violetta Naughton, Peter R. Flatt, Carel W. Le Roux, Neil G. Docherty, Charlotte R. Moffett
Summary: Modification of gut-islet secretions after Roux-En-Y gastric bypass surgery contributes to its metabolic and anti-diabetic benefits. Limited knowledge exists on tissue-specific hormone distribution post-surgery and how it compares with medical treatment. This study provides insights into the cellular adaptations following surgery and medical treatment that contribute to the amelioration of obesity-diabetes phenotype in an animal model.
Article
Medicine, Research & Experimental
Julie Turbitt, Lorraine Brennan, R. Charlotte Moffett, Peter R. Flatt, Paul R. V. Johnson, Andrei I. Tarasov, Neville H. McClenaghan
Summary: The study found that taurine, alanine, and proline can promote insulin secretion through the regulation of ion transport and inhibition of the sodium-potassium-chloride cotransporter. This action of taurine may have potential value in the treatment of diabetes.
Article
Endocrinology & Metabolism
Vadivel Parthsarathy, Christopher Hogg, Peter R. Flatt, Finbarr P. M. O'Harte
DIABETES OBESITY & METABOLISM
(2018)
Article
Biochemistry & Molecular Biology
Dawood Khan, Srividya Vasu, R. Charlotte Moffett, Victor A. Gault, Peter R. Flatt, Nigel Irwin
BIOLOGICAL CHEMISTRY
(2018)