Development of nuclear medicine methods for gastric and small bowel motility : effects of GLP-1 on gastric emptying

The diagnosis of functional disorders of the gastrointestinal (GI) tract requires techniques being both sufficiently sensitive to detect disturbances of the normal physiology and low-invasive enough not to interfere with the properties being studied. The purpose was to set up nuclear medicine methods for assessment of upper GI tract motility and study the effect of glucagon-like peptide-1 (GLP-1) on gastric emptying.

Study I: In order to establish a national standard for solid gastric emptying with reference values, eight Swedish centres were included in a multicentre project, each providing 20 healthy subjects. A standardised meal consisting of a 99mTc-labelled omelet and an unlabelled soft drink was defined and reference values were established. Sub-group analysis showed that premenopausal women had a slower gastric emptying than postmenopausal women, why separate reference values should be used. Menstrual cycle, smoking habits or body mass index (BMI) within the normal range did not influence gastric emptying.

Study II: Previous studies have shown incongruent results with regard to the influence of obesity on gastric emptying. This was studied in 9 obese subjects (BMI>35 kg/m 2) and in 21 normal weight controls, using the method developed in study I. An association between obesity and increased gastric emptying was found.

Study III: GLP-1 is secreted from the intestinal mucosa in the presence of nutrients and acts as an incretin. An inhibitory effect of GLP-1 on upper GI motility has been shown using non-imaging techniques. The effect of iv. administered GLP-1 on gastric solid emptying was studied in 8 healthy subjects. GLP-1 had an inhibitory effect on all phases of solid gastric emptying. Analysis of pancreatic and intestinal hormones showed that peptide YY (PYY) levels decreased during GLP-1 infusion which may be due to a negative feedback mechanism. Comparison with the scintigraphic images revealed that GLP-1 release started when the head of the meal was in the jejunum.

Study IV: The effect of GLP-1 on non-nutrient gastric emptying is unclear. The effect of iv. administered GLP-1 on gastric liquid emptying was studied in 7 healthy subjects. GLP-1 had a powerful inhibitory effect on liquid gastric emptying and also influenced the gastric distribution of liquids. No effect on water homeostasis was observed.

Study V: There is no available technique for small bowel transit examination without taking the stomach emptying into account. For this purpose, a technique based on biliary scintigraphy with 99mTc-HIDA was developed and evaluated against simultaneously performed hydrogen breath test in 30 healthy subjects. Radiotracer appearance in the duodenum and caecum, respectively, were taken for start- and endpoints of transit. There was a good correlation between transit times assessed by 99mTc-HIDA scintigraphy and hydrogen breath test, but the latter showed significant longer transit times due to the passage through the stomach. The technique may easily be set up at any nuclear medicine department where it can serve as a primary step in the evaluation of a suspected GI motor disorder.

Nuclear medicine techniques represent a feasible tool for upper GI motility examinations both in clinical and research settings. The radiation dose is low and commonly available gamma cameras can be used. In addition to reported data, such techniques are used at present for several other studies of the effect of various GI peptides.

List of scientific papers

I. Gryback P, Hermansson G, Lyrenas E, Beckman KW, Jacobsson H, Hellstrom PM (2000). "Nationwide standardisation and evaluation of scintigraphic gastric emptying: reference values and comparisons between subgroups in a multicentre trial." Eur J Nucl Med 27(6): 647-55
https://pubmed.ncbi.nlm.nih.gov/10901450

II. Gryback P, Naslund E, Hellstrom PM, Jacobsson H, Backman L (1996). "Gastric emptying of solids in humans: improved evaluation by Kaplan-Meier plots, with special reference to obesity and gender. " Eur J Nucl Med 23(12): 1562-7
https://pubmed.ncbi.nlm.nih.gov/8929308

III. Naslund E, Bogefors J, Skogar S, Gryback P, Jacobsson H, Holst JJ, Hellstrom PM (1999). "GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans." Am J Physiol 277(3 Pt 2): R910-6
https://pubmed.ncbi.nlm.nih.gov/10484511

IV. Naslund E, Bogefors J, Gryback P, Bjellerup P, Jacobsson H, Holst JJ, Hellstrom PM (2001). "GLP-1 inhibits gastric emptying of water but does not influence plasma. " Scand J Gastroenterol 36(2): 156-62
https://pubmed.ncbi.nlm.nih.gov/11252407

V. Gryback P, Jacobsson H, Blomquist L, Schnell PO, Hellstrom PM (2002). "Scintigraphy of the small intestine: a simplified standard for study of transit with reference to normal values. " Eur J Nucl Med Mol Imaging 29(1): 39-45. Epub 2001 Nov 22
https://pubmed.ncbi.nlm.nih.gov/11807605