Related Experiment Video
Updated: Jan 3, 2026

High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
Published on: January 23, 2018
Activation of the HIF1α/PFKFB3 stress response pathway in beta cells in type 1 diabetes
Hiroshi Nomoto1, Lina Pei1, Chiara Montemurro1
1Larry L. Hillblom Islet Research Center, David Geffen School of Medicine at UCLA, University of California Los Angeles, 10833 Le Conte Avenue, 33-165 CHS, Los Angeles, CA, 90095-7073, USA.
Aims/Hypothesis:
The conserved hypoxia inducible factor 1 α (HIF1α) injury-response pro-survival pathway has recently been implicated in early beta cell dysfunction but slow beta cell loss in type 2 diabetes. We hypothesised that the unexplained prolonged prediabetes phase in type 1 diabetes may also be, in part, due to activation of the HIF1α signalling pathway.
Methods:
RNA sequencing (RNA-Seq) data from human islets with type 1 diabetes or after cytokine exposure in vitro was evaluated for activation of HIF1α targets. This was corroborated by immunostaining human pancreases from individuals with type 1 diabetes for 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), the key effector of HIF1α-mediated metabolic remodelling, and by western blotting of islets and INS-1 832/13 cells exposed to cytokines implicated in type 1 diabetes.
Results:
HIF1α signalling is activated (p = 4.5 × 10-9) in islets from individuals with type 1 diabetes, and in human islets exposed in vitro to cytokines implicated in type 1 diabetes (p = 1.1 × 10-14). Expression of PFKFB3 is increased fivefold (p < 0.01) in beta cells in type 1 diabetes and in human and rat islets exposed to cytokines that induced increased lactate production. HIF1α attenuates cytokine-induced cell death in beta cells.
Conclusions/Interpretation:
The conserved pro-survival HIF1α-mediated injury-response signalling is activated in beta cells in type 1 diabetes and likely contributes to the relatively slow rate of beta cell loss at the expense of early defective glucose-induced insulin secretion.
Related Concept Videos
Psychoneuroimmunology: Diabetes and Cancer
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
Insulin and C-peptide are...
Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...
Insulin Secretory Vesicles
Cell Specific Gene Expression
Insulin: The Receptor and Signaling Pathways

