Pseudo‐hyperglucagonemia was observed in pancreatectomized patients when measured by glucagon sandwich enzyme‐linked immunosorbent assay

Kobayashi, Masaki; Waki, Hironori; Nakayama, Hitomi; Miyachi, Atsushi; Mieno, Eri; Hamajima, Hitoshi; Goto, Minoru; Yamada, Kentaro; Yamauchi, Toshimasa; Kadowaki, Takashi; Kitamura, Tadahiro

doi:10.1111/jdi.13325

Cited by 8 publications

(7 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 28 , 29 However, when GLP-1 secretion is high, some glucagon assays cross-react with longer proglucagon-derived species containing the glucagon sequence, particularly glicentin, leading to debate over whether the gut ever releases intact glucagon. 30 , 31 In addition to these reports from populations with altered pathology, and although we were unable to find active glucagon in human intestinal tissue by LC-MS, 32 our data suggest that some healthy people may also exhibit post-OGTT glucagon elevation.…”

Section: Discussionsupporting

confidence: 47%

Expected values for gastrointestinal and pancreatic hormone concentrations in healthy volunteers in the fasting and postprandial state

et al. 2020

View full text Add to dashboard Cite

Background: Gastrointestinal hormones regulate intestinal transit, control digestion, influence appetite and promote satiety. Altered production or action of gut hormones, including total glucagon-like peptide-1 (total GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and peptide YY (PYY), may contribute to the biological basis of obesity and altered glucose homeostasis. However, challenges in analytical methodology and lack of clarity on expected values for healthy individuals has limited progress in this field. The aim of this study was to describe expected concentrations of gastrointestinal and pancreatic hormones in healthy volunteers following a standardised meal test (SMT) or 75g oral glucose tolerance test (OGTT). Methods: 28 healthy volunteers (12 men, 16 women; mean age 31.3 years; mean body mass index 24.9 kg/m2) were recruited to attend a hospital clinic on two occasions. Volunteers had blood sampling in the fasting state and were given, in randomised order, an oral glucose tolerance test (OGTT) and standardised mixed liquid meal test with venepuncture at timed intervals for 4 hours after ingestion. Analytical methods for gut and pancreatic hormones were assessed and optimised. Concentrations of gut and pancreatic hormones were measured and used to compile ranges of expected values. Results: Ranges of expected values were created for glucose, insulin, glucagon, total GLP-1, GIP, PYY and free fatty acids in response to a standardised mixed liquid meal or OGTT. Intact Proinsulin and C-peptide levels were also measured following the OGTT. Conclusions: These ranges of expected values can now be used to compare gut hormone concentrations between healthy individuals and patient groups.

show abstract

Section: Discussionsupporting

confidence: 47%

Expected values for gastrointestinal and pancreatic hormone concentrations in healthy volunteers in the fasting and postprandial state

et al. 2020

View full text Add to dashboard Cite

show abstract

“…15,16 Thus, it has been reported that in the case of elevated proglucagon-derived peptide levels, such as after bariatric surgery or pancreatectomy, the currently used ELISA shows falsely high glucagon values due to cross-reactivity with these peptides. [16][17][18] In order to solve this problem, a modified protocol of the currently used ELISA has been reported. 16,17 As an alternative, we have developed a new sandwich ELISA using newly developed monoclonal antibodies against glucagon.…”

Section: Introductionmentioning

confidence: 99%

“…However, the currently used ELISA still has cross‐reactivities with proglucagon‐derived peptides due to their remaining non‐specific reaction with the antibodies used in this system 15,16 . Thus, it has been reported that in the case of elevated proglucagon‐derived peptide levels, such as after bariatric surgery or pancreatectomy, the currently used ELISA shows falsely high glucagon values due to cross‐reactivity with these peptides 16–18 . In order to solve this problem, a modified protocol of the currently used ELISA has been reported 16,17 …”

Section: Introductionmentioning

confidence: 99%

A newly developed glucagon sandwich ELISA is useful for more accurate glucagon evaluation than the currently used sandwich ELISA in subjects with elevated plasma proglucagon‐derived peptide levels

Kobayashi

Maruyama

Yamamoto

et al. 2023

J of Diabetes Invest

Self Cite

View full text Add to dashboard Cite

Aims/Introduction: Glucagon, a peptide hormone produced from proglucagon, is involved in the pathophysiology of diabetes. Plasma glucagon levels are currently measured by sandwich enzyme-linked immunosorbent assay (ELISA), but the currently used sandwich ELISA cross-reacts with proglucagon-derived peptides, thereby providing incorrect results in subjects with elevated plasma proglucagon-derived peptide levels. We aimed to develop a more broadly reliable ELISA for measuring plasma glucagon levels. Materials and Methods: A new sandwich ELISA was developed using newly generated monoclonal antibodies against glucagon. After its validation, plasma glucagon levels were measured with the new ELISA and the currently used ELISA in subjects who underwent laparoscopic sleeve gastrectomy (LSG) and in outpatients with suspected glucose intolerance. The ELISA results were compared with those from liquid chromatography-high resolution mass (LC-HRMS) analysis, which we previously established as the most accurate measuring system. Results: The new ELISA has high specificity (<1% cross-reactivities) and high sensitivity (a lower range of 0.31 pmol/L). Plasma glucagon values in the subjects who underwent laparoscopic sleeve gastrectomy and some outpatients with suspected glucose intolerance differed between the new ELISA and the currently used ELISA. These subjects also showed markedly high plasma glicentin levels. Despite the elevated plasma glicentin levels, the new ELISA showed better positive correlation with LC-HRMS than did the currently used ELISA. Conclusions: The new ELISA enables more accurate measurement of plasma glucagon than the currently used ELISA, even in subjects with elevated proglucagon-derived peptide levels. It should be clinically useful in elucidating the pathophysiology of individual diabetic patients.

show abstract

“…It is reported that postprandial pseudohyperglucagonemia could be displayed when the plasma glucagon level was measured by glucagon sandwich ELISA after partial but large pancreatectomy (oneseventh of the pancreas remaining) and total pancreatectomy, possibly due to the cross-reactivity of glucagon antibodies to the remaining gut-derived glicentin [35]. In the current study, we could not exactly evaluate the dissected and remaining volumes of pancreatic parenchyma.…”

Section: Discussionmentioning

confidence: 63%

Different post-pancreatectomy glucagon responses to a meal test between surgical approaches

Matsuda,

Himeno,

Nakashima

et al. 2023

Endocr J

View full text Add to dashboard Cite

Residual pancreatic endocrine function is important for maintaining metabolic status after pancreatectomy and is closely related to patient nutritional status and prognosis. In contrast to insulin secretion, the significance of glucagon secretion following pancreatectomy remains unclear. In this study, we assessed the changes in pancreatic glucagon secretion during pancreatectomy to determine their pathophysiological significance. We evaluated glucagon and insulin secretion using a liquid meal tolerance test before and after pancreatectomy in patients scheduled to undergo pancreaticoduodenectomy (PD) or distal pancreatectomy (DP). After pancreatectomy, fasting plasma glucagon levels were significantly decreased in both the PD (n = 10) and DP (n = 5) groups (PD: from 18.4 to 10.5 pg/mL, p = 0.037; DP: from 21.0 to 12.1 pg/mL, p = 0.043), whereas postprandial plasma glucagon levels were not changed. In the liquid meal tolerance test after pancreatectomy, 60-min plasma glucagon levels and the area under the curve (AUC) for 0-120 min of PD were significantly higher than those for DP (60-min plasma glucagon: PD 49.0 vs. DP 21.7 pg/mL, p = 0.040; AUC 0-120min : PD 4,749 vs. DP 3,564 μg min/mL, p = 0.028). Postoperative plasma glucose, serum insulin, and serum C-peptide levels during the liquid meal tolerance test were not significantly different between the two groups. Although fasting plasma glucagon levels decreased, postprandial glucagon responses were maintained after both PD and DP. The difference in residual meal-stimulated glucagon response between PD and DP suggests that a relative excess of postprandial glucagon is involved in the postoperative nutritional status after PD through its impact on systemic metabolic status.

show abstract

Pseudo‐hyperglucagonemia was observed in pancreatectomized patients when measured by glucagon sandwich enzyme‐linked immunosorbent assay

Cited by 8 publications

References 10 publications

Expected values for gastrointestinal and pancreatic hormone concentrations in healthy volunteers in the fasting and postprandial state

Expected values for gastrointestinal and pancreatic hormone concentrations in healthy volunteers in the fasting and postprandial state

A newly developed glucagon sandwich ELISA is useful for more accurate glucagon evaluation than the currently used sandwich ELISA in subjects with elevated plasma proglucagon‐derived peptide levels

Different post-pancreatectomy glucagon responses to a meal test between surgical approaches

Contact Info

Product

Resources

About