Title:Possible Hypoxia Signaling Induced Alteration of Glucose Homeostasis in Rats Exposed to Chronic Intermittent Hypoxia - Role of Antioxidant (Vitamin C) and Ca2+ Channel Blocker (Cilnidipine)
VOLUME: 11 ISSUE: 1
Author(s):Kusal K. Das, Santosh R. Nemagouda, Satish G. Patil and Sikha Saha
Affiliation:Laboratory of Vascular Physiology & Medicine, Department of Physiology, Shri B.M. Patil Medical College, Hospital and Research Centre, BLDE University, Bijapur-586103, Karnataka, India.
Keywords:Chronic intermittent hypoxia, HIF-1α, malondialdehyde, glucose homeostasis, vitamin c, cilnidipine.
Abstract:Background: Hyperglycemia is found to be a regulator of HIF-1α gene expression but the
regulation of HIF-1α on glucose homeostasis is unclear.
Objective: To determine whether chronic intermittent hypoxia (CIH) alters glucose regulation and such alterations can
revert through treatments with either antioxidant (vitamin c) or calcium channel blocker (cilnidipine) in male albino rats.
Methods: The rats were divided into six groups i.e. normoxia (21% oxygen), CIH (10% oxygen with cycle time 3:1.5;
8h/day), normoxia with vitamin c (50 mg /100g. b.wt, orally), CIH with vitamin c, normoxia with cilnidipine
(1 mg/kg/day; ip) and CIH with cilnidipine. Serum MDA, HIF-1α, fasting plasma glucose, insulin, GTT, HOMA-IR and
insulinogenic index were evaluated.
Results: Serum HIF-1α and MDA concentration in rats exposed to CIH increased significantly whereas simultaneous CIH
with vitamin c and CIH with cilnidipine treatment show reversion of both serum HIF- 1α and MDA concentrations
towards normoxic status. CIH rats showed increased fasting glucose level with unchanged plasma insulin level but both
vitamin c and cilnidipine treatment improved the status. Elevated HOMA-IR and insulinogenic index along with impaired
GTT were found in CIH groups although vitamin c and cilnidipine improved the glucose homeostasis in CIH exposed
rats.
Conclusion: CIH induces over production of reactive oxygen species as well as hyper activities of sympathetic N-type
Ca2+ channels possibly through HIF 1-α expression and influence on insulin signaling by causing hyperglycemia, glucose
intolerance and insulin resistance in rats. Simultaneous treatment with vitamin c or cilnidipine improves glucose
homeostasis in CIH exposed rats.
