Serum levels of ghrelin and LEAP2 in patients with type 2 diabetes mellitus: correlation with circulating glucose and lipids

Abstract

Objective: Ghrelin regulates body weight, food intake and blood glucose. It also regulates insulin secretion from pancreatic islet cells. LEAP2 is a newly discovered endogenous ligand of growth hormone secretagogue’s receptor (GHSR). It not only antagonizes the stimulation of GHSR by ghrelin but also inhibits constitutive activation of GHSR as an inverse agonist. Type 2 diabetes (T2D) patients have endocrine disorders with metabolic imbalance. Plasma levels of ghrelin and LEAP2 may be changed in obese and T2D patients. However, there is no report yet on circulating LEAP2 levels or ghrelin/LEAP2 ratio in T2D patients. In this study, fasting serum ghrelin and LEAP2 levels in healthy adults and T2D patients were assessed to clarify the association of two hormones with different clinical anthropometric and metabolic parameters. Design: A total of 16 females and 40 males, ages 23-68 years old normal (n = 27) and T2D patients (n = 29) were enrolled as a cross-sectional cohort. Results: Serum levels of ghrelin were lower but serum levels of LEAP2 were higher in T2D patients. Ghrelin levels were positively correlated with fasting serum insulin levels and HOMA-IR in healthy adults. LEAP2 levels were positively correlated with age and HbA1c in all tested samples. Ghrelin/LEAP2 ratio was negatively correlated with age, fasting blood glucose and HbA1c. Conclusions: This study demonstrated a decrease in serum ghrelin levels and an increase in serum LEAP2 levels in T2D patients. LEAP2 levels were positively correlated with HbA1c, suggesting that LEAP2 was associated with T2D development. The ghrelin/LEAP2 ratio was closely associated with glycemic control in T2D patients showing negative correlation with glucose and HbA1c.

Plasma LEAP-2 Following a Low-Calorie Diet with or without Interval Exercise in Women with Obesity

“…Indeed, during energy deficit LEAP-2 has been reported to decline in effort to raise blood glucose for the prevention of hypoglycemia via a potential influence of glucagon mediated hepatic glucose production [ 12 ]. This would be consistent with observations that higher plasma LEAP-2 has been associated with higher HbA1c in T2D [ 21 ]. In our work, fasting glucose levels tended to decrease post-treatment, as did C-peptides.…”

“…The novelty here is LCD and LCD+INT appear to differentially impact glucose-stimulated-LEAP-2 stimulation. Thus, our work extends on prior work using acute stimuli to induce changes in LEAP-2 [ 14 , 20 ] or cross-sectional data of different health status [ 21 ] by showing short-term training during an energy deficit does not alter reduction-s in LEAP-2 during the fasting state, 24 h after the last exercise bout but does potentially influence post-prandial responses among women with obesity.…”

“…Furthermore, we covaried for fat mass loss and treatment effects remained. Instead, reductions in LEAP-2 have been linked to elevations in fat utilization [ 14 , 20 , 21 ] and ketone bodies [ 14 ]. We did not measure ketone bodies in our study per se, but we did detect higher circulating fasting FFAs following both LCD and LCD+INT and prior work by our group reported elevated fasting fat oxidation [ 18 ].…”

Feeding-induced hepatokines and crosstalk with multi-organ: A novel therapeutic target for Type 2 diabetes

“…It's possible that the interaction between Ghrelin and Leap2 performs a significant part in the progression of T2DM. There is some speculation that the ghrelin-Leap2 axis could be a viable therapeutic target for T2D (96). In conclusion, we came to the view that Leap2 has the possibility to be an applicable treatment for the control of T2DM.…”

“…The reduction in serum ghrelin levels and the elevation of Leap2 levels in individuals with type 2 diabetes may represent a physiological compensation as a response to a positive energy balance to maintain a normal energy balance. Lowering the Ghrelin/Leap2 ratio in individuals with T2DM may lower the overactivation of the GHSR in obese patients, which in turn may restore normal energy homeostasis (96). This viewpoint is reinforced by a paper that showed improvements in obesity and diabetes when levels of acyl ghrelin were reduced, levels of Leap2 were increased, or GHSR activity was blocked (173).…”