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. 2020 May;68(2):448-457.
doi: 10.1007/s12020-020-02233-4. Epub 2020 Mar 2.

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

Hai-Yan Wu #  1 , Nai-Shi Li #  2 , Yu-Li Song  1 , Chun-Mei Bai  3 , Qiang Wang  1 , Yu-Pei Zhao  4 , Yu Xiao  5 , Shuang Yu  1 , Ming Li  2 , Yuan-Jia Chen  6
Affiliations

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

Hai-Yan Wu et al. Endocrine. 2020 May.

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.

Keywords: BMI; Ghrelin; Growth hormone secretagogue receptor (GHS-R); Insulin; Insulinoma; Obesity.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
a Plasma levels of acylated ghrelin in patients with insulinoma and in control group. Acylated ghrelin levels in patients with insulinoma were significantly lower than that in the control groups [median 15 (5–35) vs.19 (6–47), P = 0.016], (mean ± SD 16.3 ± 8.2 vs. 22.0 ± 9.5). b Each dot represents an individual level of ghrelin in each patient
Fig. 2
Fig. 2
a Obesity could influence the plasma levels of acylated ghrelin in patients with insulinoma and control group. Plasma levels of acylated ghrelin in obese patients (BMI ≥ 29 kg/m2) were significantly lower than that in the obese controls [median 15 (6–27) pg/ml vs. 24 (6–35) pg/ml, P = 0.029], (mean ± SD 15.9 ± 7.7 vs. 21.1 ± 9.7). b Each dot represents an individual level of ghrelin in each patient
Fig. 3
Fig. 3
a Plasma levels of acylated ghrelin in patients with higher levels of insulin/proinsulin were significantly lower than that in patients with normal levels of insulin/proinsulin [median 15 (5–35) pg/ml vs. 19 (6–47) pg/ml, P = 0.028]. b Each dot represents an individual level of ghrelin in each patient
Fig. 4
Fig. 4
HE and immunohistochemical staining of ghrelin and its functional receptor GHS-R1A in insulinoma tissues and paired para-tumoral tissues. Left panel: HE staining; middle panel: ghrelin IHC, 10×; right panel: GHS-R1A IHC, 10×. scale bar, 100 μm. HE staining on an insulinoma tissue (a); positive IHC staining of ghrelin and its receptor GHS-R1A (b and c, respectively), in the same tumor tissue, shown the negative immunostaining of ghrelin and GHS-R1A in interstitial tissues (b and c); HE staining on another insulinoma (d) and its paired para-tumoral tissues (g); shown the negative IHC staining of ghrelin and its receptor GHS-R1A (e and f, respectively), in the same tumor tissue, while positive expression of ghrelin and its receptor GHS-R1A can be seen in islets within its paired para-tumoral tissue (h and i, respectively). Black arrows indicating pancreatic islets (g, h, and i)
Fig. 5
Fig. 5
a Plasma levels of acylated ghrelin in patients with expression of ghrelin in insulinomas were not significantly different from that in patients without expression of ghrelin in tumor tissues [median 11 (6–31) pg/ml vs. 12.5 (7–18) pg/ml, P = 0.740]. bEach dot represents an individual level of ghrelin in each patient
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