7 December 2023

A gut feeling for hormones

Gastrointestinal peptides, such as GLP-1, GIP, and glicentin, are crucial players in the field of metabolic diseases, both as agonists and antagonists. In the pursuit of innovative treatments for conditions like diabetes and obesity, these peptides have become the focus of extensive research.


Cutting-edge assays

At Mercodia, we are at the forefront of providing cutting-edge assays for gut hormones, enabling researchers and healthcare professionals to investigate deeper into the complexities of metabolic diseases. Our commitment to precision ensures that your findings are accurate and reliable, paving the way for advancements in the field. 

GLP-1 

GLP-1 (Glucagon-like peptide 1) has as main action to stimulate insulin secretion. It is derived from proglucagon in intestinal L-cells and exists in two biologically active forms: GLP-1 (7-36) amide and GLP-1 (7-37). These forms, however, face a short half-life due to rapid degradation by the enzyme Dipeptidyl Peptidase IV (DPP4). The enzymatic processing, catalyzed by DPP4, results in the forms GLP-1 (9-36) amide and GLP-1 (9-37)1,2

Total GLP-1 ELISA (10-1278-01)

GIP 

GIP (Gastric inhibitory polypeptide) was the first incretin identified. Derived through proteolytic processing of a precursor called preproGIP, its main effect is to stimulate insulin secretion in response to a meal and it is involved in lipid metabolism3. Found in intestinal K cells, GIP 1-42 (active GIP) undergoes rapid cleavage in circulation at the N-terminus by DPP4, resulting in GIP 3-42, considered a non-active form of GIP¹. 

Total GIP ELISA (10-1258-01)

Glicentin  

Glicentin is a proglucagon-derived peptide primarily produced in L-intestinal cells following food intake. Comprising the complete sequence of glucagon, GRPP, and oxyntomodulin, glicentin holds promise as a biomarker for predicting weight loss post-bariatric surgery 4,5. Among its biological actions, glicentin can stimulate insulin secretion and inhibit acid secretion. 

Glicentin ELISA (10-1273-01)

Total vs. active: Navigating the problem

Understanding the complexity of gut hormones requires distinguishing between active and total forms. The rapid cleavage of active GIP/GLP-1 in circulation by DPP4 requires the measurement of both intact and DPP4-metabolized forms to comprehensively study their secretion and processing in vivo

The significance of amidated forms of GLP-1 

While both active forms of GLP-1 have demonstrated comparable biological potency, it is interesting that the predominant circulating form in humans is the amidated version. Therefore, it is important to measure this isoform at 100% for accurate assessments6. Using methods with minimal cross-reactivity to the prevailing metabolite is crucial to avoid underestimation, ensuring precise detection of fluctuations and changes in plasma concentrations7.

Recent publications using Total GLP-1 ELISA, Total GIP ELISA, and Glicentin ELISA from Mercodia

GLP1 references 

  • Uddén Hemmingsson J, Leijonmarck CE, Klingvall M. Postbariatric hypoglycemia in symptomatic versus asymptomatic patients: proposals for clinical assessments. BMJ Open Diabetes Res Care. 2022;10(5):e002572.
  • Jiang H, Pang S, Zhang Y, et al. A phase 1b randomised controlled trial of a glucagon-like peptide-1 and glucagon receptor dual agonist IBI362 (Ly3305677) in Chinese patients with type 2 diabetes. Nat Commun. 2022;13:3613.
  • Halkjær SI, de Knegt VE, Kallemose T, et al. No effect of multi-strain probiotic supplementation on metabolic and inflammatory markers and newborn body composition in pregnant women with obesity: Results from a randomized, double-blind placebo-controlled study. Nutr Metab Cardiovasc Dis. 2023;33(12):2444-2454.
  • Chen L, Zhang J, Sun Y, et al. A phase I open-label clinical trial to study drug-drug interactions of Dorzagliatin and Sitagliptin in patients with type 2 diabetes and obesity. Nat Commun. 2023;14(1):1405.
  • Mellbye FD, Hermansen K, Jeppesen PB, Gregersen S. Acute effects of the coffee diterpene cafestol on glucose metabolism in non-diabetic subjects with abdominal obesity. Rev Diabet Stud. 2023;19(2):34-42.

GIP references 

  • Mellbye FD, Hermansen K, Jeppesen PB, Gregersen S. Acute effects of the coffee diterpene cafestol on glucose metabolism in non-diabetic subjects with abdominal obesity. Rev Diabet Stud. 2023;19(2):34-42.
  • Fritsche L, Heni M, Eckstein SS, et al. Incretin hypersecretion in gestational diabetes mellitus. J Clin Endocrinol Metab. 2022;107(6):e2425-e2430.
  • Hummel J, Fritsche L, Vosseler A, et al. Free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation. Sci Rep. 2021;11(1):16642.
  • Mose M, Møller N, Jessen N, et al. Β-lactoglobulin is insulinotropic compared with casein and whey protein ingestion during catabolic conditions in men in a double-blinded randomized crossover trial. J Nutr. 2021;151(6):1462-1472.
  • Vestergaard ET, Zubanovic NB, Rittig N, et al. Acute ketosis inhibits appetite and decreases plasma concentrations of acyl ghrelin in healthy young men. Diabetes Obes Metab. 2021;23(8):1834-1842.

Glicentin references 

  • Fritsche L, Heni M, Eckstein SS, et al. Incretin hypersecretion in gestational diabetes mellitus. J Clin Endocrinol Metab. 2022;107(6):e2425-e2430.
  • Perakakis N, Kokkinos A, Angelidi AM, et al. Circulating levels of five proglucagon-derived peptides in response to intravenous or oral glucose or lipids and to a mixed-meal in subjects with normal weight, overweight, and obesity. Clin Nutr. 2022;41(9):1969-1976.
  • Fanni G, Katsogiannos P, Nandi Jui B, et al. Response of multiple hormones to glucose and arginine challenge in T2DM after gastric bypass. Endocr Connect. 2022;11(8):e220172.
  • Hummel J, Fritsche L, Vosseler A, et al. Free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation. Sci Rep. 2021;11(1):16642.
  • Wewer Albrechtsen NJ, Kjeldsen SAS, Jensen NJ, et al. On measurements of glucagon secretion in healthy, obese, and Roux-en-Y gastric bypass operated individuals using sandwich ELISA. Scand J Clin Lab Invest. 2022;82(1):75-83.

References

  1. Seino et al.; Journal of Diabetes Investigation; 2010 
  2. Holst JJ.; Physiol Rev.; 2007 
  3. Tiffany Y, et al.; Academic Press; 2018 
  4. Perakakis, N. et al. Metabolism 2019 
  5. Nielsen, M. S. et al.; Clin. Endocrinol. Metab.; 2020 
  6. Ørskov, et al.; J Biol Chem; 1989 
  7. Ørskov et al.; Diabetes; 1994 

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