Altered circadian responses to light in streptozotocin-induced diabetic mice

1999 ◽  
Vol 277 (2) ◽  
pp. E232-E237 ◽  
Author(s):  
Etienne Challet ◽  
Olivier van Reeth ◽  
Fred W. Turek

Diabetes mellitus affects the daily expression of many behavioral and metabolic processes. Recent studies indicate that changes in brain glucose metabolism alter the entraining effects of light of the circadian pacemaker. To test whether diabetes-associated diurnal changes are related to alterations in the responses of the circadian pacemaker to light, photic phase resetting of the circadian rhythm of locomotor activity was analyzed in diabetic mice housed in constant darkness. Multiple low doses of streptozotocin, which damages pancreatic β-insulin-producing cells, were used to render C57BL/6J mice mildly diabetic. In those mice treated with streptozotocin, serum glucose was increased by 25% and circadian responses to light either were increased by 40% for phase delays or were close to those observed in control animals for phase advances. Furthermore, insulin-induced hypoglycemia normalized light-induced phase delays in diabetic animals, without altering those in nondiabetic mice. These results show that abnormalities of daily temporal organization associated with diabetes can result from altered circadian responses to the daily variation in ambient light. Such alterations could be normalized with appropriate insulin therapy.

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3262
Author(s):  
Nada Oršolić ◽  
Damir Sirovina ◽  
Dyana Odeh ◽  
Goran Gajski ◽  
Vedran Balta ◽  
...  

Diabetic dyslipidemia and hyperglycemia contribute to excessive reactive oxygen species (ROS) production, leading to deleterious complications, such as nephropathy, atherosclerosis and cardiac dysfunction, and target major organs in the body. The aim of this study was to investigate the effect of caffeic acid (CA) on mouse weight and survival, serum level of fasting blood glucose (FBG), serum lipid parameters and atherogenic indices, oxidative damage in blood, liver and kidney tissue, pathophysiological changes and their function markers in healthy and alloxan-induced type 1 diabetic mice. Diabetes was induced in mice with a single intravenous injection of alloxan (75 mg kg−1). Two days later, CA (50 mg kg−1) was given intraperitoneally for seven days in diabetic mice. Diabetes affected glucose level, lipid profile, hematological and biochemical parameters, induced DNA damage and apoptotic/necrotic death in whole blood cells, liver and kidney, leading to weight loss and a decreased lifespan. CA treatment of diabetic mice revealed a protective effect on the liver and kidney, hypoglycemic and hypolipidemic properties and high protection against atherogenic outcomes. The obtained results suggest that CA is a safe and potent agent against diabetes that acts as an effective antioxidant in reducing serum glucose, lipid profile and atherogenic indices, leading to increased lifespan in mice.


1993 ◽  
Vol 265 (5) ◽  
pp. R1199-R1204 ◽  
Author(s):  
T. Hamada ◽  
S. Shibata ◽  
A. Tsuneyoshi ◽  
K. Tominaga ◽  
S. Watanabe

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus appears to act as a circadian clock. The SCN vasoactive intestinal polypeptide-like immunoreactive neurons, which may act to mediate photic information in the SCN, receive input from neurons immunoreactive for somatostatin (SST). Therefore we investigated the role of SST as a transmitter for entrainment by analyzing the phase-resetting effect of SST on the circadian rhythm of SCN firing activity. Perfusion of SST increased 2-deoxyglucose uptake at circadian time (CT) 18, but not at CT6. A 1-h or 15-min treatment with SST produced phase delays when it was administered at CT13-14 and phase advances at CT22-23. Thus SST-induced phase changes are similar to those for light pulses to animals under constant darkness. The present findings suggest that SST is a transmitter for mediating information of entrainment to circadian clocks within the SCN.


1996 ◽  
Vol 270 (1) ◽  
pp. R271-R282 ◽  
Author(s):  
E. B. Klerman ◽  
D. J. Dijk ◽  
R. E. Kronauer ◽  
C. A. Czeisler

The sensitivity of the human circadian system to light has been the subject of considerable debate. Using computer simulations of a recent quantitative model for the effects of light on the human circadian system, we investigated these effects of light during different experimental protocols. The results of the simulations indicate that the nonuniform distribution over the circadian cycle of exposure to ordinary room light seen in classical free-run studies, in which subjects select their exposure to light and darkness, can result in an observed period of approximately 25 h, even when the intrinsic period of the subject's endogenous circadian pacemaker is much closer to 24 h. Other simulation results suggest that accurate assessment of the true intrinsic period of the human circadian pacemaker requires low ambient light intensities (approximately 10-15 lx) during scheduled wake episodes, desynchrony of the imposed light-dark cycle from the endogenous circadian oscillator, and a study length of at least 20 days. Although these simulations await further experimental substantiation, they highlight the sensitivity to light of the human circadian system and the potential confounding influence of light on the assessment of the intrinsic period of the circadian pacemaker.


1999 ◽  
Vol 276 (4) ◽  
pp. R1063-R1070 ◽  
Author(s):  
Etienne Challet ◽  
Susan Losee-Olson ◽  
Fred W. Turek

To test whether circadian responses to light are modulated by decreased glucose availability, we analyzed photic phase resetting of the circadian rhythm of locomotor activity in mice exposed to four metabolic challenges: 1) blockade of glucose utilization induced by 2-deoxy-d-glucose (2-DG), 2) fasting (food was removed for 30 h), 3) insulin administration, and 4) insulin treatment after fasting. In mice housed in constant darkness, light pulses applied during early subjective night induced phase delays of the rhythm of locomotor activity, whereas light pulses applied during late subjective night caused phase advances. There was an overall reduction of light-induced phase shifts, with a more pronounced effect for delays, in mice pretreated with 500 mg/kg ip 2-DG compared with mice injected with saline. Administration of glucose with 2-DG prevented the reduction of light-induced phase delays. Furthermore, phase delays were reduced in fed mice pretreated with 5 IU/kg sc insulin and in fasted mice injected with saline or insulin compared with control fed mice. These results show that circadian responses to light are reduced when brain glucose availability is decreased, suggesting a metabolic modulation of light-induced phase shifts.


2019 ◽  
Vol 34 (2) ◽  
pp. 154-166 ◽  
Author(s):  
Nadia Saderi ◽  
Adrián Báez-Ruiz ◽  
Lucia E. Azuara-Álvarez ◽  
Carolina Escobar ◽  
Roberto C. Salgado-Delgado

The circadian system drives the temporal organization of body physiology in relation to the changing daily environment. Shift-work (SW) disrupts this temporal order and is associated with the loss of homeostasis and metabolic syndrome. In a rodent model of SW based on forced activity in the rest phase for 4 weeks, we describe the occurrence of circadian desynchrony, as well as metabolic and liver dysfunction. To provide better evidence for the impact of altered timing of activity, this study explored how long it takes to recover metabolic rhythms and behavior. Rats were submitted to experimental SW for 4 weeks and then were left to recover for one week. Daily locomotor activity, food intake patterns, serum glucose and triglycerides, and the expression levels of hepatic Pparα, Srebp-1c, Pepck, Bmal1 and Per2 were assessed during the recovery period and were compared with expected data according to a control condition. SW triggered the circadian desynchronization of all of the analyzed parameters. A difference in the time required for realignment was observed among parameters. Locomotor activity achieved the expected phase on day 2, whereas the nocturnal feeding pattern was restored on the sixth recovery day. Daily rhythms of plasma glucose and triglycerides and of Pparα, Pepck and Bmal1 expression in the liver resynchronized on the seventh day, whereas Srebp-1c and Per2 persisted arrhythmic for the entire recovery week. SW does not equally affect behavior and metabolic rhythms, leading to internal desynchrony during the recovery phase.


2000 ◽  
Vol 526 (3) ◽  
pp. 695-702 ◽  
Author(s):  
Jamie M. Zeitzer ◽  
Derk‐Jan Dijk ◽  
Richard E. Kronauer ◽  
Emery N. Brown ◽  
Charles A. Czeisler

Sign in / Sign up

Export Citation Format

Share Document