Positive Correlation of Galanin With Glucose in Type 2 Diabetes

Compelling literature (1) has been accumulated regarding the action of galanin as an incretin on insulin secretion. Although galanin inhibits glucose-stimulated insulin release in animals, no such effect has been documented in humans (2). Actually, galanin administration in humans has been shown to suppress the initial postprandial rise in plasma concentration of glucose and insulin (3) with unaltered glucose-stimulated insulin release (2). Nevertheless, basal plasma galanin levels have been shown to diverge with obesity and hormonal status.

We enrolled 21 patients with type 2 diabetes (HbA_1c 7.8 ± 1.19%): 9 men (aged 54.6 ± 3.87 years, BMI 28.5 ± 1.6 kg/m²) and 12 postmenopausal women (follicle-stimulating hormone [FSH] >30 mIU/ml, aged 55.6 ± 3.8 years, BMI 28.4 ± 2.9 kg/m²) with a maximum disease duration of 4 years. Twenty-four healthy individuals participated in the study as control subjects: 12 men (aged 55.3 ± 3.1 years, BMI 27.4 ± 2.2 kg/m²) and 12 women (FSH >30 mIU/ml, aged 54.17 ± 3.4 years, BMI 28.19 ± 2.2 kg/m²) with no history of diabetes, hypertension, liver, or kidney disease. None of the nondiabetic healthy volunteers were taking any medication, and none had a first-degree relative with type 2 diabetes. Written informed consent was obtained from all study participants. Blood samples were collected at rest at 8:00 a.m., after an overnight fast and 24-h alcohol abstention. Human galanin (hGal) (1) was determined by a radioimmunoassay (Peninsula Laboratories, Belmont, CA). Insulin was measured by an enzyme-linked immunosorbent assay (AxSYM; Abbott Laboratories, North Chicago, IL). A two-site sandwich immunoassay, using direct chemiluminescent technology (ADVIA Centaur; Bayer, Leverkusen, Germany) was used for the determination of serum C-peptide.

Interestingly, a statistically significant increase of hGal was found in both women and men with type 2 diabetes compared with control subjects (women 25.6 ± 5.4 vs. 12.2 ± 0.3 pg/ml, P < 0.001; men 22.4 ± 2.01 vs. 12.2 ± 1.14 pg/ml, P < 0.001).

Additionally, a strong positive correlation of hGal with glucose (r = 0.963, P < 0.001) and HbA_1c (r = 0.903, P < 0.001) was recorded in the women with type 2 diabetes. In men with type 2 diabetes, the above correlation, though statistically significant, was less strong (P = 0.05 and 0.04, respectively).

The increment of insulin was shown in both type 2 diabetic men and women, as compared with control subjects (women 20.36 ± 2.89 vs. 4.0 ± 1.30 μIU/ml, P = 0.002; men 15 ± 3.1 vs. 4.36 ± 1.97 μIU/ml, P < 0.001), whereas C-peptide was increased significantly only in the women with type 2 diabetes (3.1 ± 1.2 ng/ml vs. 1.3 ± 0.4 ng/ml, P = 0.001). Of note, insulin showed a significant negative correlation with glucose only in the women.

In conclusion, a strong positive correlation of hGal has been established with glucose in the fasting state. Galanin appears to be related to the presence of type 2 diabetes and not to the patient’s obesity and hormonal status.