Disruption of Circadian Rhythms Accelerates Development of Diabetes Through Pancreatic Beta-Cell Loss and Dysfunction

J Biol Rhythms. 2011 Oct;26(5):423-33. doi: 10.1177/0748730411416341.

Abstract

Type 2 diabetes mellitus (T2DM) is complex metabolic disease that arises as a consequence of interactions between genetic predisposition and environmental triggers. One recently described environmental trigger associated with development of T2DM is disturbance of circadian rhythms due to shift work, sleep loss, or nocturnal lifestyle. However, the underlying mechanisms behind this association are largely unknown. To address this, the authors examined the metabolic and physiological consequences of experimentally controlled circadian rhythm disruption in wild-type (WT) Sprague Dawley and diabetes-prone human islet amyloid polypeptide transgenic (HIP) rats: a validated model of T2DM. WT and HIP rats at 3 months of age were exposed to 10 weeks of either a normal light regimen (LD: 12:12-h light/dark) or experimental disruption in the light-dark cycle produced by either (1) 6-h advance of the light cycle every 3 days or (2) constant light protocol. Subsequently, blood glucose control, beta-cell function, beta-cell mass, turnover, and insulin sensitivity were examined. In WT rats, 10 weeks of experimental disruption of circadian rhythms failed to significantly alter fasting blood glucose levels, glucose-stimulated insulin secretion, beta-cell mass/turnover, or insulin sensitivity. In contrast, experimental disruption of circadian rhythms in diabetes-prone HIP rats led to accelerated development of diabetes. The mechanism subserving early-onset diabetes was due to accelerated loss of beta-cell function and loss of beta-cell mass attributed to increases in beta-cell apoptosis. Disruption of circadian rhythms may increase the risk of T2DM by accelerating the loss of beta-cell function and mass characteristic in T2DM.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Circadian Rhythm / physiology*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Humans
  • Insulin / metabolism
  • Insulin Resistance
  • Insulin Secretion
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / physiology*
  • Islet Amyloid Polypeptide / physiology
  • Male
  • Motor Activity
  • Photoperiod
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Transgenic

Substances

  • Blood Glucose
  • Insulin
  • Islet Amyloid Polypeptide