1606-P: Effect of Changes in Dark/Light Cycle on Physiological Homeostasis as a Confounding Prelude to Diabetes in Fischer 334 Animal Model

Abstract

Understanding the role of modern life-style driven disruption in circadian rhythm can advance appropriate management of the shift in physiological homeostasis that may lead to groups of diseases such as diabetes. This study was carried out to determine the effect of light period changes on this possible shift using Fischer 344 rat model. Animals were split into 3 groups of 6 Males and 6 Females each: G I for normal light period (6 am to 6 pm); G II for reversed light period (6 pm to 6 am on alternate weeks); G III was G I with additional 8 h light period (6 pm to 2 am on alternate days). Daily feed, water intake and weekly body weight was recorded. Elevated plus maze for anxiety was done on day 21. On day 22, blood glucose, cholesterol, triglycerides and ACTH were measured. Histopathology of pancreas was done. Results showed no statistical difference in body weights of both sexes in G II and III. However, females in G III had 7% higher body weight than G I. Feed intake increased by 39.7% in both sexes in G III compared to G II. Water intake decreased by 7.2% in G II and 3.4% in G III compared to G I indicating change in normal physiology. G III showed increased blood glucose (38.4%), cholesterol (34.2%), and triglycerides (77.8%). In G III males ACTH was elevated by 38.9% while the same effect was seen in G II females (27.1%). Open arm behavior analysis decreased was by 24.9% in G III compared to G I indicating animals in a state of anxiety. G I Pancreas showed normal islets of Langerhans; G II with swollen acinar cells with vacuoles in few; G III with additional cellular degeneration of islets of Langerhans. Study indicates less adaptation capacity of Fisher 344 rats to disruption in light period as evidenced (p value <0.05) by changes in ACTH, blood chemistry, cellular morphology and behavioral pattern suggesting a shift in physiological homeostasis that may lead to group of diseases such as diabetes. Further investigation is underway to ascertain associated beta cell function and molecular changes. Disclosure B. Subramanian: None. G. Ramakrishnan: None. P. Tamilmaran: None. B. Sundarakrishnan: None. K. Seshadri: None. Funding Primer Academy of Medical Sciences (PAMS-CAReTS-SBV)