Circadian rhythm-related genes: implication in autoimmunity and type 1 diabetes

Recent gene association and functional studies have proven the implication of several circadian rhythm-related genes in diabetes. Diabetes has been related to variation in central circadian regulation and peripheral oscillation. Different transcriptional regulators have been identified. Circadian genes are clearly implicated in metabolic pathways, pancreatic function and in type 2 diabetes. Much less evidence has been shown for the link between circadian regulation and type 1 diabetes. The hypothesis that circadian genes are involved in type 1 diabetes is reinforced by findings that the immune system undergoes circadian variation and that several autoimmune diseases are associated with circadian genes. Recent findings in the non-obese diabetic mouse model pinpoint to specific mechanisms controlling type 1 diabetes by the clock-related gene Arntl2 in the immune system.

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There is growing evidence about the implication of the circadian rhythm in diabetes development. Studies in mice have shown that the disruption of circadian rhythms can accelerate diabetes and -cell loss.

In humans a link between the central circadian rhythm regulation and glucose homeostasis has been suggested by findings such as the polymorphism in MTNR1B, encoding the melatonin receptor 1B, that increases the risk for type 2 diabetes. Transcription and translation of core clock components circadian locomotor output cycles kaput (CLOCK), aryl hydrocarbon receptor nuclear translocator-like 1 (ARNTL1), aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2), period circadian proteins (PER1, PER2, PER3) and Cryptochromes (CRY1 and CRY2) play a pivotal role in rhythm generation in the suprachiasmatic nucleus, which is the site of the master circadian oscillator in mammals, but also in the control of peripheral oscillations.

Authors: B. Lebailly1,2, C. Boitard1 & U. C. Rogner1

  1. Institut Cochin (INSERM U1016, CNRS UMR-S8104, Département “Endocrinologie, Métabolisme et Diabètes), Paris, France
  2. Cellule Pasteur, University Pierre and Marie Curie, Paris, France

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