Immunohistochemical studies in the experimental diabetic hippocampus in relation with cognitive impairments

Abstract

We have previously shown that the elevated plasma ghrelin accelerate emptying in the early stage of diabetes in rats. However, it remains unknown whether plasma ghrelin levels are still elevated in the late stage of diabetes. We studied whether solid gastric emptying and plasma ghrelin levels are altered 2–8 weeks after streptozotocin (STZ) injection. The development of autonomic neuropathy was evaluated by spectral analysis of heart rate variability (HRV). Gastric emptying was not different between control and diabetic rats at 4 weeks and 6 weeks, while it delayed at 8 weeks in STZ rats. The pre-prandial ghrelin levels were not significantly different between control and diabetic rats at 4–8 weeks. In control rats, the plasma ghrelin levels were significantly reduced 30 min after the feeding at 4–8 weeks. In contrast, there was no significant reduction of ghrelin levels observed in diabetic rats at 4–8 weeks. Plasma insulin levels were significantly increased 30 min after feeding in control rats, but not STZ rats, at 4–8 weeks. Both HF (parasympathetic activity) and LF (sympathetic activity) component were gradually reduced 6–8 weeks after STZ injection. It is suggested that hypoinsulinemia associated with diabetes increases plasma ghrelin levels. At the late stage of diabetes, gastric emptying is delayed despite increased plasma ghrelin levels. The delayed gastric emptying is mainly due to impaired activity of autonomic nerves at the late stage of diabetes.