The Regulation Of Circulating Insulin Level By Hypoxia Stress

Insulin is involved in the glycometabolism of the people and animals. Blood glucose level directly regulates insulin secretion. We researched and found that the severe hypoxia significantly decreased animals' food intake and body weight gain, and the hypoxia caused that the animals' glycometabolism in vivo turned to anaerobic glycolysis from aerobic oxidation, which led to consuming a great quantity of glucose, and animals' blood glucose levels decreased. Hypoxia, especially, how does the continual hypoxia influence insulin secretion? And whether is the activated HPA axis by hypoxia involved or not in the regulation of insulin secretion? We simulated the effect of hypoxia of the different altitude height (2 km and 5 km) and different time on insulin secretion utilizing the cabins of low pressure oxygen. The insulin, glucagon and somatostatin contents or levels in plasma and pancreas, and plasma leptin and corticosterone levels of rats were detected by radioimmunoassay (RIA) method. Plasma glucose concentration and pancreatic glucose contents were measured by glucose oxidase method. The hepatic glycogen contents were determined by anthrone method. Simultaneously, 5 km continual hypoxia for 5 days was researched, and CRFR1,CRFR2 and SS were involved in the regulation of insulin secretion. The experimental results as following:1. Effects of intermittent hypoxia, cold, restraint and their combinated stresses on the level of insulin secretionSimulated 2 km intermittent hypoxia (4 hours/day, continuation for 15 days) didn't significantly influence rats' body weight gain. However, simulated 5 km intermittent hypoxia (4 hours/day, continuation for 15 days) significantly inhibited rats' body weight gain. Alone cold stress, simulated 2 km hypoxia stress (4 hours/day, continuation for 2 days) + cold, 2 km hypoxia stress, 2 km hypoxia stress + restraint stress and alone restraint stress all significantly decreased rats' body weight gain. Among the stresses, the inhibition of restraint stress is most obvious, but the five stresses didn't significantly influence the levels of plasma insulin in rats. Compared to the respectively alone stress, cold + 5 km hypoxia (4 hours/day, continuation for 2 days) and restraint + 5 km hypoxia combinated stresses significantly inhibited body weight gain of rats, and the five stresses also markedly decreased hepatic glycogen contents, and increased plasma glucagon levels.2. Effect of continual hypoxia on the level of insulin secretionCompared to the sea level normoxia control group, simulated continual 2 km hypoxia for 1-25 days (1, 2, 5, 10,15 and 25 days) did not significantly influence rats' body weight, food intake and plasma insulin level. But the 2 km hypoxia significantly increased hepatic glycogen content and blood glucose level on day 2 of hypoxia, plasma glucagon level on day 10, corticosterone level on day 1 and plasma leptin levels on day 1 and 2, however significantly decreased plasma leptin level on day 5. Compared to the sea level normoxia control group, simulated continual 5 km hypoxia for 1-25 days (1, 2, 5, 10, 15 and 25 days) significantly decreased rats' body weight and food intake. Continual 5 km hypoxia markedly reduced hepatic glycogen contents on day 1 and 2 of hypoxia, significantly decreased blood glucose levels on day 5, 10, 15 and 25, significantly decreased plasma insulin levels on day 2, 5, 10 and 15, significantly increased plasma glucagon level day 2, significantly increased plasma leptin levels on day 1 and 2, respectively, whereas significantly decreased plasma leptin on day 5, significantly increased plasma corticosterone levels on day 1 till 15.3. Corticotrophin-releasing factor receptor type 1 (CRFR1) was involved in the regulation of the level of hypoxia-inhibited insulin secretionCompared to the sea level normoxia control group + vehicle group, simulated continual 5 km hypoxia for 5 days significantly decreased rats' body weight, food intake, blood glucose level, pancreatic glucose content and plasma insulin level, also markedly increased pancreatic insulin content and plasma corticosterone level. Compared to the hypoxia group + vehicle group, the pretreatment with CP-154,526 + hypoxia further significantly decreased glucose and reversed the decrease of hypoxia- inhibited pancreatic glucose and plasma insulin level and the increase of plasma glucagon level, also reversed the increase of plasma corticosterone level. Compared to the CP-154,526 control group, CP-154,526 + simulated continual 5 km hypoxia for 5 days significantly decreased body weight, blood glucose and plasma glucagon level, and significantly increased pancreatic glucose and insulin contents.4. Corticotrophin-releasing factor receptor type 2 (CRFR2) was involved in the regulation of the level of insulin secretion under hypoxia stressCompared to the sea level normoxia control + vehicle group, Antisauvagine-30 antagonist (30μg/kg) + simulated continual 5 km hypoxia group for 4 hours significantly increased blood glucose level of rats, also significantly decreased plasma insulin level. And hypoxia group, hypoxia + AS-30 antagonist (20μg/kg) group and hypoxia + AS-30 antagonist (30μg/kg) group significantly decreased food intake, and hypoxia significantly decreased plasma corticosterone level. Hypoxia + AS-30 antagonist (30μg/kg) group further decreased food intake.5. Somatostatin was involved in the regulation of the level of hypoxia-inhibited insulin secretionCompared to the sea level normoxia control + vehicle group, simulated continual 5 km hypoxia for 1-10 days (1, 2, 5 and 10 days) significantly decreased rats' body weight and food intake, significantly decreased blood glucose levels on day 5 and 10, significantly increased pancreatic glucose contents on day 1 and 2, but significantly decreased pancreatic glucose contents on day 5 and 10, significantly decreased plasma insulin levels and significantly increased pancreatic insulin contents on day 5 and 10, significantly increased plasma glucagon level on day 2, significantly increased plasma somatostatin levels and pancreatic somatostatin contents. Compared to the 5 km hypoxia + vehicle group, the pretreatment with CSH-HCl + simulated continual 5 km hypoxia group fuether decreased body weight and food intake on day 1 and 5, completely reversed the reduction of blood glucose level and the increase of pancreatic insulin content on day 5, and decrease plasma glucagon levels on day 1 and 5, reversed the increase of plasma somatostatin contents on day 1 and 5. Compared to the CSH-HC1 control group, the pretreatment with CSH-HCl + simulated continual 5 km significantly decreased body weight and food intake, significantly decreased blood glucose, plasma insulin, pancreatic insulin and plasma glucagon on day 5, but significantly increased pancreatic somatostatin content.Conclusion:1. Simulated 2 km intermittent hypoxia (4 hours/day, continuation for 2 days), cold, restraint and their compound stresses did not obviously influence rats' insulin secretion.2. Simulated 5 km continual hypoxia significantly inhibited insulin secretion of rats, which depended on the hypoxic time and hypoxic intensity. The inhibitory action correlated with the hypoxia-caused lower blood glucose and higher corticosterone levels.3. The inhibition of rats' insulin secretion correlated with the corticotrophin-releasing factor receptor type 1.4. Somatostatin was also involved in hypoxia-inhibited insulin secretion.