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Ghrelin in Diabetes
Elevated Ghrelin plasma levels and preproghrelin up-regulation
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Ghrelin-related products |
The physiological activities of Ghrelin with respect to obesity and food intake regulation are well documented amongst the obesity research community. However, application of Ghrelin in diabetes mellitus remains an enigma. A December 2002 study published by Ishii and co-workers and a March 2003 study by Masaoka and co-workers investigated the effects on ghrelin levels of rats with streptozotocin-induced diabetes. Their results showed an elevated level of Ghrelin in the bloodstream and an increase in gastric preproghrelin mRNA expression levels in the stomachs of the streptozotocin-induced diabetic rats. Inversely, gastric Ghrelin levels and Ghrelin-immunoreactive cells in the gastric fundus decreased significantly. These findings indicate the potential of diabetes in up-regulating preproghrelin mRNA expression levels and stimulated Ghrelin synthesis and secretion in the stomach.
Role of Ghrelin in Streptozotocin-Induced Diabetic Hyperphagia
Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue
receptor, was originally purified from the rat stomach. We have previously
reported that central administration of ghrelin increases food intake
and body weight. To investigate the role of ghrelin in the hyperphagia
response to uncontrolled diabetes, adult male rats were studied 14 days
after administration of streptozotocin (STZ) or vehicle. STZ-treated diabetic
rats were markedly hyperphagic. This hyperphagia was accompanied by hyperglycemia,
hypoinsulinemia, and reduced plasma GH levels. Treatment of diabetic rats
with insulin reversed these changes. Plasma ghrelin concentrations in
untreated diabetic rats were significantly higher than in control rats
and were normalized by insulin treatment. The ghrelin gene expression
in the stomach was also higher in STZ diabetic rats. This reduction in
plasma leptin levels was reversed by insulin treatment. In addition, hypothalamic
NPY mRNA levels were increased in STZ-treated diabetic rats and were reversed
by insulin treatment. Furthermore, the hyperphagia was partially reversed
by the administration of a ghrelin-receptor antagonist. Therefore, we
conclude that the elevated plasma ghrelin levels, along with decreased
plasma leptin levels, could contribute to the diabetic hyperphagia in
part by increasing hypothalamic NPY. This is the first report to show
the pathophysiological significance of ghrelin in diabetes.
S. Ishii et al. Endocrinology 2002; 143(12): 4934-7
Enhanced plasma ghrelin levels in rats with streptozotocin-induced diabetes
Ghrelin is a novel gastrointestinal peptide that stimulates growth hormone secretion, food intake, and body weight gain. Increased ghrelin secretion has been reported in such negative energy states as starvation and low body weight. We investigated the dynamics of ghrelin in rats with streptozotocin-induced diabetes, because they represent reduced body weight and hyperphagia. The plasma ghrelin levels and gastric preproghrelin mRNA expression levels of the diabetic rats increased significantly and their gastric ghrelin levels decreased significantly. Negative energy balance may enhance preproghrelin MRNA expression and ghrelin secretion into the bloodstream.
T. Masaoka et al. FEBS Letters 2003; 541:64-68
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