ArticleDiabetologia2012
Lactogens protect rodent and human beta cells against glucolipotoxicity-induced cell death through Janus kinase-2 (JAK2)/signal transducer and activator of transcription-5 (STAT5) signalling.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- p21-senescent cells drive pancreatic islet dysfunction through targetable paracrine signaling in type 2 diabetes.JCI insight · 2026Article
- c-Jun regulates postpartum β-cell apoptosis and survival downstream of prolactin signaling.Molecular and cellular endocrinology · 2025Article
- NRF2 deficiency leads to inadequate beta cell adaptation during pregnancy and gestational diabetes.Redox biology · 2025Article
- LGR4 is essential for maintaining β-cell homeostasis through suppression of RANK.Molecular metabolism · 2025Article
- Magnetogenetic cell activation using endogenous ferritin.bioRxiv : the preprint server for biology · 2024Article
- RANKL/RANK is required for cytokine-induced beta cell death; osteoprotegerin, a RANKL inhibitor, reverses rodent type 1 diabetes.Science advances · 2023Article
- Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro.Biomolecules · 2022Article
- The Human Islet: Mini-Organ With Mega-Impact.Endocrine reviews · 2021Review
- Dynamic Regulation of JAK-STAT Signaling Through the Prolactin Receptor Predicted by Computational Modeling.Cellular and molecular bioengineering · 2021Article
- Lactogens Reduce Endoplasmic Reticulum Stress-Induced Rodent and Human β-Cell Death and Diabetes Incidence in Akita Mice.Diabetes · 2020Article
- Placental Lactogen as a Marker of Maternal Obesity, Diabetes, and Fetal Growth Abnormalities: Current Knowledge and Clinical Perspectives.Journal of clinical medicine · 2020Review
- Lrrc55 is a novel prosurvival factor in pancreatic islets.American journal of physiology. Endocrinology and metabolism · 2019Article
- Stigmasterol prevents glucolipotoxicity induced defects in glucose-stimulated insulin secretion.Scientific reports · 2017Article
- Augmented Stat5 Signaling Bypasses Multiple Impediments to Lactogen-Mediated Proliferation in Human β-Cells.Diabetes · 2015Article
- Human Islets Have Fewer Blood Vessels than Mouse Islets and the Density of Islet Vascular Structures Is Increased in Type 2 Diabetes.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2015Article
- The study of women, infant feeding and type 2 diabetes after GDM pregnancy and growth of their offspring (SWIFT Offspring study): prospective design, methodology and baseline characteristics.BMC pregnancy and childbirth · 2015Article
- Osteoprotegerin and Denosumab Stimulate Human Beta Cell Proliferation through Inhibition of the Receptor Activator of NF-κB Ligand Pathway.Cell metabolism · 2015Article
- Human islet preparations distributed for research exhibit a variety of insulin-secretory profiles.American journal of physiology. Endocrinology and metabolism · 2015Article
- Milk consumption during pregnancy increases birth weight, a risk factor for the development of diseases of civilization.Journal of translational medicine · 2015Review
- Knockdown of prolactin receptors in a pancreatic beta cell line: effects on DNA synthesis, apoptosis, and gene expression.Endocrine · 2014Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
aims/hypothesisA leading cause of type 2 diabetes is a reduction in functional beta cell mass partly due to increased beta cell death, triggered by stressors such as glucolipotoxicity (GLT). This study evaluates the hypothesis that lactogens can protect beta cells against GLT and examines the mechanism behind the pro-survival effect.
methodsThe effect of exogenous treatment or endogenous expression of lactogens on GLT-induced beta cell death was examined in INS-1 cells, and in rodent and human islets. The mechanism behind the pro-survival effect of lactogens was determined using an inhibitor, siRNAs, a dominant negative (DN) mutant, and Cre-lox-mediated gene deletion analysis.
resultsLactogens significantly protect INS-1 and primary rodent beta cells against GLT-induced cell death. The pro-survival effect of lactogens in rodent beta cells is mediated through activation of the Janus kinase-2 (JAK2)/signal transducer and activator of transcription-5 (STAT5) signalling pathway. Lactogen-induced increase in the anti-apoptotic B cell lymphoma-extra large (BCLXL) protein is required to mediate its pro-survival effects in both INS-1 cells and primary rodent beta cells. Most importantly, lactogens significantly protect human beta cells against GLT-induced cell death, and their pro-survival effect is also mediated through the JAK2/STAT5 pathway. CONCLUSIONS/
interpretationThese studies, together with previous work, clearly demonstrate the pro-survival nature of lactogens and identify the JAK2/STAT5 pathway as an important mediator of this effect in both rodent and human beta cells. Future studies will determine the effectiveness of this peptide in vivo in the pathophysiology of type 2 diabetes.
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