Plasma levels of acylated ghrelin in patients with insulinoma and expression of ghrelin and its receptor in insulinomas

Abstract

Background Insulinoma is a subtype of pancreatic neuroendocrine tumors. Many patients with insulinoma are obese due to frequent food intake. Ghrelin is associated with obesity and blood levels of insulin. It is not clear if plasma levels of ghrelin in insulinoma patients correlate with hyperinsulinemia and obesity. Expression of ghrelin and its receptor has not been well demonstrated in insulinoma. Objective To study if plasma levels of ghrelin is associated with obesity and hyperinsulinemia or hyperproinsulinemia in patients with insulinoma, and to detect the expression of ghrelin and its receptor in insulinoma. Methods Plasma levels of acylated ghrelin, insulin, and proinsulin were measured in 37 patients with insulinoma and 25 controls by ELISA. Expression of ghrelin and its receptor GHS-R1A was examined in 20 insulinoma and paired pancreatic specimens by immunostaining. P ≤ 0.05 was considered significant. Results The plasma levels of acylated ghrelin in patients with insulinoma were significantly lower than that in the controls (median 15 pg/ml vs. 19 pg/ml, respectively, P = 0.016). The reduced plasma levels of acylated ghrelin in patients were significantly correlated with obesity, hyperinsulinemia, and hyperproinsulinemia (P = 0.029 and P = 0.028, respectively). Expression of ghrelin and its receptor GHS-R1A was shown in the majority of insulinoma specimens. The expression of GHS-R1A was positively correlated with ghrelin expression in insulinoma (P = 0.014). Conclusions Plasma levels of acylated ghrelin decreased in patients with insulinoma, probably due to the hyperinsulinemia and obesity in the patients. Expression of both ghrelin and its receptor is common in insulinoma.

The regulation of gastric ghrelin secretion

“…Similarly, a recent study demonstrated that circulating AG levels are reduced in patients with insulinoma 146 . Patients with these neuroendocrine tumours often present insulin over secretion, which has been suggested to reduce gastric ghrelin release 146 . However, patients with insulinoma are frequently obese 147 .…”

“…Therefore, a secretory interaction between these glucoregulatory hormones seems reasonable, with most clinical studies reporting an inhibitory effect of insulin on TG release 127‐129 . Similarly, a recent study demonstrated that circulating AG levels are reduced in patients with insulinoma 146 . Patients with these neuroendocrine tumours often present insulin over secretion, which has been suggested to reduce gastric ghrelin release 146 .…”

“…However, patients with insulinoma are frequently obese 147 . Therefore, lower circulating AG levels in these patients may also be explained by the characteristic decrease in circulating ghrelin levels in obesity 146 . Furthermore, various mechanistic studies using the isolated rat stomach have demonstrated a consistent insulin‐dependent suppression of TG release 50,131,148 .…”

Insulinoma after sleeve gastrectomy: A case report

“…Ghrelin and the type 1a ghrelin receptor (GHS-R1A) are expressed in different types of neuroendocrine tumors. Recently, Wu et al [ 16 ] found that GHS-R1a was found in 60% of insulinomas, suggesting that ghrelin may act through autocrine or paracrine pathways. The proliferative effects of ghrelin and its association with insulinoma have not been studied, although there is a clinical case report where a ghrelin-producing neuroendocrine tumor was transformed into an insulinoma[ 17 ].…”

The characteristics of serum lipid spectrum in PanNENs and its correlation with clinicopathological features and prognosis

“…Patients with insulinomas are often more obese, probably because of hunger or because preventing hypoglycemia prompts patients eating frequency. [33] Blood lipid levels in obese patients are characterized by increased LDL and triglyceride as well as decreased HDL in serum. [34,35] A representative survey enrolling 163,641 adults shows that women were associated with a risk of high LDL, and people older than 60 have higher TC levels.…”