UNIGE document Scientific Article
previous document  unige:31197  next document
add to browser collection

Lipotoxicity disrupts incretin-regulated human β cell connectivity

Hodson, David J
Mitchell, Ryan K
Bellomo, Elisa A
Sun, Gao
Li, Daliang
Li, Wen-Hong
show hidden authors show all authors [1 - 15]
Published in Journal of Clinical Investigation. 2013, vol. 123, no. 10, p. 4182-4194
Abstract Pancreatic β cell dysfunction is pathognomonic of type 2 diabetes mellitus (T2DM) and is driven by environmental and genetic factors. β cell responses to glucose and to incretins such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are altered in the disease state. While rodent β cells act as a coordinated syncytium to drive insulin release, this property is unexplored in human islets. In situ imaging approaches were therefore used to monitor in real time the islet dynamics underlying hormone release. We found that GLP-1 and GIP recruit a highly coordinated subnetwork of β cells that are targeted by lipotoxicity to suppress insulin secretion. Donor BMI was negatively correlated with subpopulation responses to GLP-1, suggesting that this action of incretin contributes to functional β cell mass in vivo. Conversely, exposure of mice to a high-fat diet unveiled a role for incretin in maintaining coordinated islet activity, supporting the existence of species-specific strategies to maintain normoglycemia. These findings demonstrate that β cell connectedness is an inherent property of human islets that is likely to influence incretin-potentiated insulin secretion and may be perturbed by diabetogenic insults to disrupt glucose homeostasis in humans.
PMID: 24018562
Full text
Article (Published version) (2.5 MB) - document accessible for UNIGE members only Limited access to UNIGE
Research groups La transplantation d'îlots de Langerhans (623)
Couplage cellulaire et connexines (136)
(ISO format)
HODSON, David J et al. Lipotoxicity disrupts incretin-regulated human β cell connectivity. In: Journal of Clinical Investigation, 2013, vol. 123, n° 10, p. 4182-4194. doi: 10.1172/JCI68459 https://archive-ouverte.unige.ch/unige:31197

322 hits

0 download


Deposited on : 2013-11-20

Export document
Format :
Citation style :