Table 3. Summary of studies on circulating glicentin variation in human.

Population	Aim	Glicentin detection method	Main results	References
- 83 patients who had acute pancreatitis: 30 developed abnormal glucose metabolism, 53 kept normal glucose metabolism	Explore the relationships between peptides known to be produced in both gut and brain and glucose metabolism in patients after acute pancreatitis	- Commercialized ELISA technique (Merck- Millipore®) - Plasma	- Significant decrease in glicentin, oxyntomodulin, vasoactive intestinal peptide (VIP) in individuals with abnormal glucose metabolism - Significant association between glicentin and secretin concentrations	Pendharkar et al. (45)
- 52 lean adults - 39 adults with severe or morbid obesity	Investigate serum glicentin concentrations during adult obesity and study its potential link with metabolic parameters	- Commercialized ELISA technique (Mercodia®) - Serum	- Significant decrease of glicentin concentration in patients with severe or morbid obesity compared to lean subjects - No linear correlation between glicentin concentration and body mass index, glycaemic parameters (glycaemia, insulinemia, C-peptide) or lipid parameters (total, HDL, LDL-cholesterol, triglyceride)	Raffort et al. (44)
- 30 adult patients with severe or morbid obesity, eligible to bariatric surgery: 18 patients had a Roux-en-Y Gastric Bypass (RYGB), 12 patients had a Laparoscopic Sleeve Gastrectomy (LSG), Follow-up at 3, 6 and 12 months post-surgery	Investigate fasting circulating glicentin variation in obese patients who underwent bariatric surgery	- Commercialized ELISA technique (Mercodia®) - Serum	- Significant increase of glicentin at 6 months post-surgery, with an effect more marked at 12 months - Tendency to have a more marked increase of glicentin after RYGB compared to LSG - Significant increase of glicentin/ glycaemia, glicentin/insulinemia, glicentin/C-peptide ratios after surgery - Improvement of metabolic parameters (anthropometric, glycaemic and lipidic) after surgery - No direct correlation between glicentin variation and metabolic parameters variation	Raffort et al. (43)
- 19 lean adolescents - 23 obese adolescents with normal glucose tolerance (NGT) - 19 obese adolescents with impaired glucose tolerance (IGT) - 4 obese adolescents with type 2 diabetes (T2D)	Explore fasting and postprandial plasma concentrations of the proglucagon- derived hormones (glucagon, glicentin, GLP-1) in adolescents with obesity	- Commercialized ELISA technique (Mercodia®) - Plasma	- No significant difference on fasting glicentin concentrations between lean adolescents and adolescents with obesity and NGT. - Lower fasting glicentin concentrations in adolescents with obesity and IGT compared to adolescents with obesity and NGT - Glicentin concentrations after oral glucose tolerance test (OGTT): lower in adolescents with obesity and IGT than those with NGT; peak at 30 minutes in lean adolescents and adolescents with obesity and NGT; peak at 15 minutes in adolescents with obesity and IGT;peak at 60 minutes in adolescents with obesity and T2D - Ratios of glicentin/glucagon and GLP-1/ glucagon: in fasting: lower ratios in obese adolescents with IGT and T2D than obese adolescents with NGT; during OGTT: lower ratios in obese adolescents with NGT than lean adolescents and lower ratios in obese adolescents with IGT and T2D than obese adolescents with NGT - Fasting plasma glicentin as a predictor of IGT in adolescents with obesity and normal fasting glucose: 100% sensitivity and 56% specificity	Manell et al. (42)
- 21 very-low-birthweight infants: 11 infants had early feeding with breast milk within 24h after birth, 10 infants had breast milk more than 24h after birth	Explore the effects of early enteral feedings and the secretion of gut hormones in very-low- birthweight infants	- Non- commercialized sandwich ELISA - Plasma	- Glicentin basal concentration: early feeding group: higher glicentin concentrations at day 5-6 and day 14 after birth than at day 1 – 2; control group: higher glicentin concentrations at day 14 after birth than at day 1 – 2; higher glicentin concentrations in the early feeding group compared to controls at day 5 - 6 and day 14 after birth - Post prandial glicentin concentration: early feeding group: higher glicentin concentrations after feeding than before feeding at day 5 - 6 and day 14; control group: higher glicentin concentrations after feeding than before feeding at day 14	Shimizu et al. (41)
- 119 developing children: 21 children aged 15 to 29 days, 16 children aged 1 to 5 months, 14 children aged 6 to 11 months, 16 children aged 1 to 3 years, 17 children aged 4 to 7 years, 18 children aged 8 to 11 years, 17 children aged 12 to 15 years - Term and preterm infants: 11 term and normal birthweight, 9 low birthweight, 10 very-low-birthweight - Normal birthweight children:14 breastfed and 11 formula-fed	Investigate the changes in basal plasma concentrations of glicentin in term and preterm developing children	- Non- commercialized sandwich ELISA - Plasma	- Glicentin basal concentration: higher glicentin concentrations in children aged 15 to 29 days, 1 to 5 months versus children aged 1 to 3 years, 4 to 7 years, 8 to 11 years; higher glicentin concentrations in children aged 6 to 11 months versus children aged 1 to 3 years, 8 to 11 years, 12 to 15 years; higher glicentin concentrations in very-low-birthweight children versus normal birthweight children at day 1 or 2 after birth - Post prandial glicentin concentration: higher glicentin concentrations after feeding than before at 1 - 2 days after birth and 5 - 6 days in normal and low-birth-weight children; higher glicentin concentrations after feeding than before at 14 days after birth in very low-birth-weight children; no significant difference in glicentin concentrations between breastfed and formula-fed group	Tadokoro et al. (40)
- 6 normal subjects - 119 diabetic patients - 15 gastrectomized patients - 9 with subtotal gastrectomy, 6 with total gastrectomy, 1 with massive small bowel resection	Explore plasma concentration of glicentin in diabetic and gastrectomized patients	- Non- commercialized sandwich ELISA - Plasma	- Fasting glicentin concentration: no significant difference on plasma glicentin concentrations between normal subjects and diabetics; no correlation between glicentin concentrations and plasma glucose - Glicentin concentration after OGTT: increase of plasma glicentin in normal subjects; higher peak of glicentin at 30 min in gastrectomized patients compared to normal subjects; no significant variation of glicentin in the patient who had a massive small bowel resection	Naito et al. (39)
- 8 noninsulin-dependent diabetics (T2D) - 8 weight-matched non-diabetic controls	Identify stimuli involved in the secretion of glicentin and investigate the impact of disturbance in glucose metabolism	- Non- commercialized radioimmunoassay and chromatography - Plasma	- Fasting glicentin: mean amount of total glucagon immunoreactivity eluting at 0.3 Kd (corresponding to the elution of porcine glicentin), lower in T2D than controls - Glicentin after OGTT: increase of glicentin secretion; mean amount of total glucagon immunoreactivity eluting at 0.3 Kd (corresponding to the elution of porcine glicentin) after OGTT: higher in T2D than controls	Orskov et al. (38)
VIP - vasoactive intestinal peptide. HDL - high-density lipoprotein. LDL - low-density lipoprotein. RYGB - Roux-en-Y gastric bypass. LSG - laparoscopic sleeve gastrectomy. NGT - normal glucose tolerance. IGT - impaired glucose tolerance. T2D - type 2 diabetes. GLP-1 - glucagon like peptide 1. OGTT - oral glucose tolerance test.