Increased insulin, leptin levels suppress ghrelin action in obese patients
MedWire News: Hyperinsulinemia and hyperleptinemia may decrease circulating ghrelin levels and induce oxidative stress in obese patients with and without Type 2 diabetes, suggest researchers.
As reported in the journal Diabetes Research and Clinical Practice, Enas Hamed (Assiut University, Egypt) and colleagues recruited 30 patients with diabetes and obesity (diabesity group), 30 obese individuals without diabetes (simple obesity group), and 30 healthy controls.
They measured serum levels of fasting blood glucose (FBG), postprandial blood glucose, lipid peroxide (LPO), nitric oxide (NO), insulin, leptin, and ghrelin among the participants.
The authors found that the fasting serum level of ghrelin was significantly lower in simple obese patients (11.97 ng/ml) and in patients with diabesity (11.39 ng/ml), compared with the healthy participants (45.13 ng/ml).
Homeostasis model assessment of insulin resistance (HOMA-IR) and leptin levels were significantly higher in obese patients (3.38 and 23.73 ng/ml, respectively) and in patients with diabesity (10.46 and 25.48 ng/ml), compared with the control group (1.50 and 7.08 ng/ml).
The researchers say the lower ghrelin levels observed in obese patients with and without diabetes compared with controls may be explained by elevated insulin, as previous research has shown insulin to be a potent inhibitor of ghrelin secretion.
They also report that ghrelin was negatively correlated with NO in the diabesity patients.
As decreased plasma levels of ghrelin and increased oxidative stress have previously been reported in obese patients, it is not surprising that there is an inverse relationship between them, say the authors.
In addition, insulin resistance (HOMA-IR ≥2.6) was found in 76.7% of the simple obese patients and in 93.3% of the diabesity patients, and fasting leptin positively correlated with FBG in these insulin-resistant individuals.
"Leptin regulates appetite control and energy metabolism, is strongly correlated with obesity, and may play a major role in islet growth and insulin secretion," say the authors.
Furthermore, the authors found that patients with simple obesity or diabesity had significantly increased LPO serum levels of 6.37 and 6.08 µmol/l, compared with 4.11 µmol/l in healthy individuals. LPO levels also correlated positively with insulin levels and insulin resistance in diabesity patients.
The authors say the findings suggest that ghrelin antagonists may be ineffective in reducing weight in obese patients with hyperinsulinemia and hyperleptinemia.
"Drugs that combine carefully balanced activities of gut and adipose tissue hormones will become the 'new wave' of diabesity therapies," concludes the team.
By Sally Robertson